Antisense oligonucleotide inhibition of hepatitis C virus gene expression in transformed hepatocytes

Genetic and biochemical studies have provided convincing evidence that the 5' noncoding region (5' NCR) of hepatitis C virus (HCV) is highly conserved among viral isolates worldwide and that translation of HCV is directed by an internal ribosome entry site (IRES) located within the 5' NCR. We have investigated inhibition of HCV gene expression using antisense oligonucleotides complementary to the 5' NCR, translation initiation codon, and core protein coding sequences. Oligonucleotides were evaluated for activity after treatment of a human hepatocyte cell line expressing the HCV 5' NCR, core protein coding sequences, and the majority of the envelope gene (E1). More than 50 oligonucleotides were evaluated for inhibition of HCV RNA and protein expression. Two oligonucleotides, ISIS 6095, targeted to a stem-loop structure within the 5' NCR known to be important for IRES function, and ISIS 6547, targeted to sequences spanning the AUG used for initiation of HCV polyprotein translation, were found to be the most effective at inhibiting HCV gene expression. ISIS 6095 and 6547 caused concentration-dependent reductions in HCV RNA and protein levels, with 50% inhibitory concentrations of 0.1 to 0.2 microM. Reduction of RNA levels, and subsequently protein levels, by these phosphorothioate oligonucleotides was consistent with RNase H cleavage of RNA at the site of oligonucleotide hybridization. Chemically modified HCV antisense phosphodiester oligonucleotides were designed and evaluated for inhibition of core protein expression to identify oligonucleotides and HCV target sequences that do not require RNase H activity to inhibit expression. A uniformly modified 2'-methoxyethoxy phosphodiester antisense oligonucleotide complementary to the initiator AUG reduced HCV core protein levels as effectively as phosphorothioate oligonucleotide ISIS 6095 but without reducing HCV RNA levels. Results of our studies show that HCV gene expression is reduced by antisense oligonucleotides and demonstrate that it is feasible to design antisense oligonucleotide inhibitors of translation that do not require RNase H activation. The data demonstrate that chemically modified antisense oligonucleotides can be used as tools to identify important regulatory sequences and/or structures important for efficient translation of HCV.     

Development of severe secondary hypertension in a patient with systemic entomophthoromycosis

The sudden onset of hypertension mandates investigation for secondary causes. We report the case of a young man with a very rare systemic fungal disease that included massive unilateral perirenal adenopathy. Treatment was associated with the abrupt onset of severe hypertension. Imaging studies suggested progressive constriction of one kidney with treatment, presumably as a result of healing adenopathy. We suggest that this case is a new example of hypertension secondary to constrictive perinephritis (Page kidney).     

CHID1 Is a Novel Prognostic Marker of Non-Small Cell Lung Cancer

There is an urgent need for identification of new prognostic markers and therapeutic targets for non-small cell lung cancer (NSCLC). In this study, we evaluated immune cells markers in 100 NSCLC specimens. Immunohistochemical analysis revealed no prognostic value for the markers studied, except CD163 and CD206. At the same time, macrophage markers iNOS and CHID1 were found to be expressed in tumor cells and associated with prognosis. We showed that high iNOS expression is a marker of favorable prognosis for squamous cell lung carcinoma (SCC), and NSCLC in general. Similarly, high CHID1 expression is a marker of good prognosis in adenocarcinoma and in NSCLC in general. Analysis of prognostic significance of a high CHID1/iNOS expression combination showed favorable prognosis with 20 months overall survival of patients from the low CHID1/iNOS expression group. For the first time, we demonstrated that CHID1 can be expressed by NSCLC cells and its high expression is a marker of good prognosis for adenocarcinoma and NSCLC in general. At the same time, high expression of iNOS in tumor cells is a marker of good prognosis in SCC. When used in combination, CHID1 and iNOS show a very good prognostic capacity for NSCLC. We suggest that in the case of lung cancer, tumor-associated macrophages are likely ineffective as a therapeutic target. At the same time, macrophage markers expressed by tumor cells may be considered as targets for anti-tumor therapy or, as in the case of CHID1, as potential anti-tumor agents.     

Color image DNA encryption using mRNA properties and non-adjacent coupled map lattices

This paper proposes a novel algorithm for encrypting color images. The innovation in this study is the use of messenger ribonucleic acid (mRNA) encoding to import into Deoxyribonucleic acid (DNA) encoding. For permutation of the plain image bits, we use Arnold’s Cat Map at the bit-level. Then, using Non-Adjacent Coupled Map Lattices (NCML), we apply diffusion operations to the permuted color channels. We also provide the upgrade of the diffusion phase with DNA encoding. In the proposed algorithm, the choices are random depending on the secret key, which is implemented using a simple logistic map. Hashing the string entered by the user, the secret key, parameters, and initial values are generated by the Double MD5 method. The results of tests and security analysis showed that the results of encryption with this scheme are effective, and the key space is large enough to withstand common attacks.

     

Improved bioavailability and pharmacokinetics of tea polyphenols by encapsulation into gelatin nanoparticles

The authors prepared surface modified (with polyelectrolyte layers), tea polyphenols (TPP) encapsulated, gelatin nanoparticles (TPP‐GNP) and characterised them. The size of the spherical nanoparticles was ∼50 nm. Number of polyelectrolyte layers and incubation time influenced the encapsulation efficiency (EE); highest EE was noted in nanoparticles with six polyelectrolyte layers (TPP‐GNP‐6L) incubated for 4 h. TPP released from TPP‐GNP‐6L in simulated biological fluids indicated protection and controlled release of TPP due to encapsulation. Mathematical modelling indicated anomalous type as a predominant mode of TPP release. TPP‐GNP‐6L exhibited enhanced pharmacokinetics in rabbit model compared with free TPP. The area under the concentration‐time curve and mean residence time were significantly higher in TPP‐GNP‐6L compared with free TPP which provide an evidence of higher bioavailability of TPP due to encapsulation. The authors demonstrated that encapsulation of TPP into GNPs favoured slow and sustained release of TPP with improved pharmacokinetics and bioavailability thereby can prolong the action of TPP.Inspec keywords: gelatin, nanoparticles, encapsulation, biomedical materials, nanomedicine, particle size, polymer electrolytes, polymer films, nanofabricationOther keywords: bioavailability, pharmacokinetics, gelatin nanoparticles, surface modified tea polyphenols, polyelectrolyte layers, spherical nanoparticle size, incubation time, encapsulation efficiency, TPP‐GNP‐6L, simulated biological fluids, mathematical modelling, TPP release, rabbit model, concentration‐time curve, mean residence time, time 4 h     

Predicting performance in ASEAN banks: an integrated fuzzy MCDM–neural network approach

This paper presents a performance assessment of 88 Association of Southeast Asian Nations banks from 2010 to 2013, using an integrated three‐stage approach on financial criteria that emulates the CAMELS rating system. More precisely, fuzzy analytic hierarchy process is used first to assess the relative weights of a number of criteria related to capital adequacy (C), asset quality (A), management quality (M), earnings (E), liquidity (L), and sensitivity to market risk (S) based on the opinion of 88 Association of Southeast Asian Nations experts. Then, these weights are used as technique for order of preference by similarity to ideal solution inputs to assess their relative efficiency. Lastly, neural networks are combined with technique for order of preference by similarity to ideal solution results to produce a model for banking performance with effective predictive ability. The results reveal that contextual variables have a prominent impact on efficiency. Specifically, parsimony in equity leveraging derived from Islamic finance principles may be the underlying cause in explaining higher efficiency levels.     

冷加工和时效处理顺序对6061铝合金力学性能的影响(英文)

研究不同的析出硬化和冷加工组合对6061铝合金拉伸性能的影响。结果表明,在不同的热处理过程中,在180℃单时效4h能提高合金的强度和伸长率。然而,双时效处理不能改善其力学性能。另外,预时效对随后的析出硬化有负面影响。合金力学性能的变化归因于析出硬化、应变硬化和加工软化的竞争而引起的显微组织演变。     

Applying a normalized ratio scale technique to assess influences of urban expansion on land surface temperature of the semi-arid city of Erbil

The difference between surface and air temperature within a city and its surrounding area is a result of variations in surface cover, thermal capacity, and 3-dimensional geometry. This research has examined and quantified the decreasing daytime land surface temperature (LST) in Erbil, Kurdistan region of Iraq, and the influence of rapid urban expansion on urban heat/cool island effect over a 20 year period. Land-use/land-cover change across this time period is also established using pixel samples. The current study proposes the application of the normalized ratio scale (NRS) to adjust the temperature of images acquired at different dates to the same range. Eleven satellite images acquired by Landsat 4, 5, 7, and 8 during the period 1992–2013 are used to retrieve LST. The results indicate that 55.3 km² of city land cover changed from bare soil to urban; consequently, the mean LST of the new urbanized area decreased by 2.28°C. The normalized difference vegetation index (NDVI) of Sami Abdul-Rahman (S.A.) Park increased from 0.09 ± 0.01 to 0.32 ± 0.11, resulting in a decrease of the mean LST by 7.29°C. This study shows that the NRS method is appropriate for detecting temperature trends from urbanization using remote-sensing data. It also highlights that urban expansion may lead to a decrease in daytime LST in drylands.     

Analysis of solar desiccant cooling system for an institutional building in subtropical Queensland,Australia

Institutional buildings contain different types of functional spaces which require different types of heating, ventilating and air conditioning (HVAC) systems. In addition, institutional buildings should be designed to maintain an optimal indoor comfort condition with minimal energy consumption and minimal negative environmental impact. Recently there has been a significant interest in implementing desiccant cooling technologies within institutional buildings. Solar desiccant cooling systems are reliable in performance, environmentally friendly and capable of improving indoor air quality at a lower cost. In this study, a solar desiccant cooling system for an institutional building in subtropical Queensland (Australia) is assessed using TRNSYS 16 software. This system has been designed and installed at the Rockhampton campus of Central Queensland University. The system's technical performance, economic analysis, energy savings, and avoided gas emission are quantified in reference to a conventional HVAC system under the influence of Rockhampton's typical meteorological year. The technical and economic parameters that are used to assess the system's viability are: coefficient of performance (COP), solar fraction, life cycle analysis, payback period, present worth factor and the avoided gas emission. Results showed that, the installed cooling system at Central Queensland University which consists of 10 m² of solar collectors and a 0.400 m³ of hot water storage tank, achieved a 0.7 COP and 22% of solar fraction during the cooling season. These values can be boosted to 1.2 COP and 69% respectively if 20 m² of evacuated tube collector's area and 1.5 m³ of solar hot water storage volume are installed.     

Fabrication of Mn–ZnO photoanodes for photoelectrochemical water splitting applications

Journal of Materials Science: Materials in Electronics - A photoelectrochemical (PEC) water splitting ability of pure ZnO and manganese-incorporated ZnO thin films fabricated via a simple...