Index Tracking with Cardinality Constraints: A Stochastic Neural Networks Approach

Partial (replication) index tracking is a popular passive investment strategy. It aims to replicate the performance of a given index by constructing a tracking portfolio which contains some constituents of the index. The tracking error optimisation is quadratic and NP-hard when taking the ℓ0 constraint into account so it is usually solved by heuristic methods such as evolutionary algorithms. This paper introduces a simple, efficient and scalable connectionist model as an alternative. We propose a novel reparametrisation method and then solve the optimisation problem with stochastic neural networks. The proposed approach is examined with S&P 500 index data for more than 10 years and compared with widely used index tracking approaches such as forward and backward selection and the largest market capitalisation methods. The empirical results show our model achieves excellent performance. Compared with the benchmarked models, our model has the lowest tracking error, across a range of portfolio sizes. Meanwhile it offers comparable performance to the others on secondary criteria such as volatility, Sharpe ratio and maximum drawdown.

The 3D reconstructed skin micronucleus assay: considerations for optimal protocol design

Implementation of the seventh amendment to the EU Cosmetics Directive has driven much research into suitable in vitro alternative assays to support satisfactory risk assessments. One such assay is the reconstructed skin micronucleus (RSMN) assay. First reported in 2006, further development occurred and a standard protocol was published in 2011. To evaluate and optimise the assay at Covance Laboratories, we tested nine chemicals [4-nitrophenol (4-NP), cyclohexanone (CH), 2-ethyl-1,3-hexanediol (2-EHD), methyl methansulfonate (MMS), mitomycin C (MMC), ethyl nitrosourea (ENU), benzo[a]pyrene (BaP), cyclophosphamide (CPA) and vinblastine (VIN)] using the EpiDerm™ 3D skin model (MatTek Corporation®, IVLSL, Bratislava, Slovakia) and compared the data using the standard 48-h treatment regimen and also an emerging 72-h treatment protocol. The EpiDerm™ tissue has reportedly some metabolic capacity but data using 48-h treatments has provided mixed results. Our investigations demonstrate that the two chemicals requiring metabolic activation (BaP and CPA) were negative following the 48-h protocol but were clearly positive following 72-h treatment. Furthermore, Replication Index (RI) data showed higher RI values in vehicle control treatments (indicating increased cell division) across the treatment set following 72-h treatments. A general greater magnitude of micronucleus (MN) induction was also observed following test chemical treatment. These data suggest that the 72-h treatment protocol is more suitable as a standard approach for the detection of clastogenic, aneugenic and metabolically activated chemicals in the RSMN assay. For further assay optimisation, we compare the statistical power of scoring cells from duplicate or triplicate cultures per treatment concentration and provide recommendations.

Protective effect of extracts of Teucrium Polium and Rumex Crispus against cyclophosphamide-induced genotoxic damage in human lymphocytes

Teucrium polium (T. polium) and Rumex crispus (R. crispus) are plant species that grow widely in Anatolia and are thought to have healing effects for many diseases. In this study plant extracts are suggested as alternative agents in repairing cellular damage by using sister chromatid exchange (SCE), micronucleus (MN), mitotic index (MI), replication index (RI) and nuclear abnormalities (NAs), against the genotoxicity of cyclophosphamide (CP) in the human lymphocyte cells. 8 experimental groups were formed in the study. The cell culture medium was supplemented with 0.16 g/ml CP and the cells were treated with 50, 100 and 250 M T. polium and R. crispus extracts in the presence and absence of CP. As a result, CP significantly decreased MI frequency while increasing SCE, MN and NAs frequencies in cells. 100 M T. polium plus CP decreased SCEs when compared with CP alone. In addition, MN frequency was significantly decreased in 100 M T. poliumplus CP and 250 M R. crispus plus CP combine groups. Our results suggest that these plant extracts are not genetically damaging and have improving effects at these doses.

Evaluation of Possible Genotoxic Activity of Dirithromycin in Cultured Human Lymphocytes

Dirithromycin antibiotic is a 14-membered lactone ring macrolide and is widely used in medicine to treat many different types of bacterial infections. In the present study, the possible genotoxicity of dirithromycin was evaluated in cultured human lymphocytes by using sister chromatid exchanges (SCEs), chromosome aberration (CA), and micronucleus (MN) tests and also cell proliferation kinetics such as mitotic index (MI), replication index (RI), and nuclear division index (NDI) were analyzed for cytotoxicity. Cell cultures were treated with four different concentrations of dirithromycin (37.75, 67.50, 125, and 250 µg/mL) for 24 and 48 h periods. Dirithromycin significantly induced SCE and MN frequency at all concentrations in both 24 and 48 h treated cells. In addition, CA level has been markedly increased in the cells treated with almost all concentrations of dirithromycin for 24 (except 37.75 µg/mL) and 48 h treatment periods as compared to control. However, MI, RI, and NDI values were not affected by the dirithromycin treatment (p> 0.05). The results of this study indicated that dirithromycin treatment caused genetic damage by increasing the level of cytogenetic endpoints, suggesting its genotoxic and mutagenic action on human lymphocytesin vitro.

Protective role of Eclipta alba L. extract against ethinylestradiol induced genotoxic damage in cultured human lymphocytes

In India, natural preparations derived from plants are widely used for the treatment of various diseases. Hence it becomes necessary to assess the modulating action of the plant extracts when associated with other substances. Ethinylestradiol is not only a genotoxic agent but also a tumor initiating agent. It is widely used in oral contraceptive formulations and also for the treatment of various sexual and metabolic disorders. In the present study, the antigenotoxic effect of Eclipta alba was evaluated against the genotoxic effect induced by 10 μM of ethinylestradiol in the presence of metabolic activation using mitotic index (MI), chromosomal aberrations, sister chromatid exchanges and replication index (RI) as parameters. The treatment of 10 μM of ethinylestradiol along with 1.02x10–4, 2.125x10–4, 3.15x10–4 and 4.17x10–4 g/mL of Eclipta alba (E. alba) extract in culture medium results in a significant dose dependent decrease in the genotoxic effects induced by the treatment of 10 μM of ethinylestradiol. The results of the present study suggest that the plant extract per se does not have genotoxic potential, but can modulate the genotoxicity of ethinylestradiol in cultured human lymphocytes.

Cytogenetic studies of methotrexate drug on the peripheral blood samples from patients suffered of ulcerative colitis & ulcerative colitis developed to pseudopolyps &colon cancer

The investigation was done on 43 samples of peripheral blood which drawn from patients suffered of chronic ulcerative colitis, 20 samples from patients of colon cancer, 10 samples from ulcerative colitis developed to pseudopolyps & 20 samples of healthy individuals. The samples were taken from female and male of different ages. The cytogenetic studies was done in order to define the damaging effects of the disease and the drug on the peripheral blood lymphocytes, these damages were manifested through the significant reduction in the blastogenic index, mitotic index, replication index, sister chromatid exchange, and mutation fraction after cells were grown in RPMI media supplemented with 10% of bovine serum, 10 microgram/ml of Budr, 0.3ml of PHA & different concentrations of drug (0.2,0.5,1,2,4,8) microgram/ml. The results indicated reduction in the blastomeric, mitotic, replication indices & mutation fraction to zero with high concentrations of the drug (1, 2, 4, 8) microgram / ml. Furthermore, the results showed presence of resistant cells with low concentration of drug (0.2, 0.5 microgram /ml) through measuring mutation fraction. Moreover, means of SCEs were increased in treated groups (patients & normal individuals) in comparison with untreated groups. Finally presence of mutated cells within low conc. of drug showed resistant to the drug in comparison with high conc. of drug which showed cytotoxic effect on the cells of the patients under investigations.

Synthesis and mutagenicity of 2-aryl-substitute (o-hydroxy-, m-bromo-, o-methoxy-, o-nitro-phenyl or 4-pyridyl) benzothiazole derivatives on Salmonella typhimurium and human lymphocytes exposed in vitro

Derivatives of 2-aryl-substitute (o-hydroxy-, m-bromo-, o-methoxy-, o-nitro-phenyl or 4-pyridyl) benzothiazole were synthesized and tested for their mutagenicity in in vitro assays: (i) in the Ames test with Salmonella typhimurium TA98 and TA100 strains; and (ii) in the sister chromatid exchange (SCE) in cultured human lymphocytes. The four of compounds (BT-11, B-12, BT-14 and BT-15) caused statistically significant increase in revertant colonies of TA98 and TA100. Treatment of lymphocytes with compounds also caused a significant increase in SCE/cell in association with high levels and long exposure (300 µg/mL and 48 h) of the four compounds. It can be concluded that benzothiazole derivatives showed mutagenic activity and were also able to exert a genotoxic effect reducing both the replication index and mitotic index.

Immunocytogenetic effects of gonadotropin releasing hormone analogue: Triptorelin Pamoate (Decapeptyl ®) during in vitro fertilization treatment

In this study, the immunocytogenetic effects of Decapeptyl ® (Triptorelin Pamoate) were assessed in the peripheral blood lymphocytes of females undergoing in vitro fertilization (IVF) treatment. Blood samples were taken from 34 females (23 treated and 11 controls), cultured and examined for sister chromatid exchanges (SCE) and cell replication index (CRI). The SCE frequency increased around ovulation time in the controls, and around the time of human chorionic gonadotropin administration in the IVF group. However, the SCE rate was significantly higher in the latter group. Furthermore, the white blood cells (WBC) count was significantly higher on the day of ovum pick up compared to the day preceding luteinizing hormone (LH) and follicle stimulating hormone (FSH) treatment. Similar observations were recorded with respect to phagocytic activity tested by nitroblue tetrazolium (NBT) assay. The nitric oxide production abilities of macrophages were not significantly changed in the LH, FSH-treated group relative to its control. Finally, the 50% complement hemolytic activity (CH50) assay results indicated that Decapeptyl lacks a significant potential to affect the complement system.