Search results for: molecular switches

Authors: E. Syngelaki, C. C. F. Schinkel, S. Klatt, E. Hörandl

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Environmental influence can alter the conditions for plant development and can trigger changes in epigenetic variation. Thus, the exposure to abiotic environmental stress can lead to different DNA methylation profiles and may have evolutionary consequences for adaptation. Epigenetic control mechanisms may further influence mode of reproduction. The alpine species R. kuepferi has diploid and tetraploid cytotypes, that are mostly sexual and facultative apomicts, respectively. Hence, it is a suitable model system for studying the correlations of mode of reproduction, ploidy, and environmental stress. Diploid and tetraploid individuals were placed in two climate chambers and treated with low (+7°C day/+2°C night, -1°C cold shocks for three nights per week) and warm (control) temperatures (+15°C day/+10°C night). Subsequently, methylation sensitive-Amplified Fragment-Length Polymorphism (AFPL) markers were used to screen genome-wide methylation alterations triggered by stress treatments. The dataset was analyzed for four groups regarding treatment (cold/warm) and ploidy level (diploid/tetraploid), and also separately for full methylated, hemi-methylated and unmethylated sites. Patterns of epigenetic variation suggested that diploids differed significantly in their profiles from tetraploids independent from treatment, while treatments did not differ significantly within cytotypes. Furthermore, diploids are more differentiated than the tetraploids in overall methylation profiles of both treatments. This observation is in accordance with the increased frequency of apomictic seed formation in diploids and maintenance of facultative apomixis in tetraploids during the experiment. Global analysis of molecular variance showed higher epigenetic variation within groups than among them, while locus-by-locus analysis of molecular variance showed a high number (54.7%) of significantly differentiated un-methylated loci. To summarise, epigenetic variation seems to depend on ploidy level, and in diploids may be correlated to changes in mode of reproduction. However, further studies are needed to elucidate the mechanism and possible functional significance of these correlations.

Keywords: apomixis, cold stress, DNA methylation, Ranunculus kuepferi

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Authors: Ayman K. El Essawy, Amal M. Hosny, Hala M. Abu Shady

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The rapid detection of TB and drug resistance, both optimizes treatment and improves outcomes. In the current study, respiratory specimens were collected from 155 patients. Conventional susceptibility testing and MIC determination were performed for rifampicin (RIF) and isoniazid (INH). Genotype MTBDRplus assay, which is a molecular genetic assay based on the DNA-STRIP technology and specific gene sequencing with primers for rpoB, KatG, and mab-inhA genes were used to detect mutations associated with resistance to rifampicin and isoniazid. In comparison to other categories, most of rifampicin resistant (61.5%) and isoniazid resistant isolates (47.1%) were from patients relapsed in treatment. The genotypic profile (using Genotype MTBDRplus assay) of multi-drug resistant (MDR) isolates showed missing of katG wild type 1 (WT1) band and appearance of mutation band katG MUT2. For isoniazid mono-resistant isolates, 80% showed katG MUT1, 20% showed katG MUT1, and inhA MUT1, 20% showed only inhA MUT1. Accordingly, 100% of isoniazid resistant strains were detected by this assay. Out of 17 resistant strains, 16 had mutation bands for katG distinguished high resistance to isoniazid. The assay could clearly detect rifampicin resistance among 66.7% of MDR isolates that showed mutation band rpoB MUT3 while 33.3% of them were considered as unknown. One mono-resistant rifampicin isolate did not show rifampicin mutation bands by Genotype MTBDRplus assay, but it showed an unexpected mutation in Codon 531 of rpoB by DNA sequence analysis. Rifampicin resistance in this strain could be associated with a mutation in codon 531 of rpoB (based on molecular sequencing), and Genotype MTBDRplus assay could not detect the associated mutation. If the results of Genotype MTBDRplus assay and sequencing were combined, this strain shows hetero-resistance pattern. Gene sequencing of eight selected isolates, previously tested by Genotype MTBDRplus assay, could detect resistance mutations mainly in codon 315 (katG gene), position -15 in inhA promotes gene for isoniazid resistance and codon 531 (rpoB gene) for rifampicin resistance. Genotyping techniques allow distinguishing between recurrent cases of reinfection or reactivation and supports epidemiological studies.

Keywords: M. tuberculosis, rpoB, KatG, inhA, genotype MTBDRplus

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Authors: A. Berraf-Tebbal, Z. Bouznad, , A.J.L. Phillips

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Phaeomoniella is a fungus genus in the mitosporic ascomycota which includes Phaeomoniella chlamydospora specie associated with two declining diseases on grapevine (Vitis vinifera) namely Petri disease and esca. Recent studies have shown that several Phaeomoniella species also cause disease on many other woody crops, such as forest trees and woody ornamentals. Two new species, Phaeomoniella zymoides and Phaeomoniella pinifoliorum H.B. Lee, J.Y. Park, R.C. Summerbell et H.S. Jung, were isolated from the needle surface of Pinus densiflora Sieb. et Zucc. in Korea. The identification of species in Phaeomoniella genus can be a difficult task if based solely on morphological and cultural characters. In this respect, the application of molecular methods, particularly PCR-based techniques, may provide an important contribution. MSP-PCR (microsatellite primed-PCR) fingerprinting has proven useful in the molecular typing of fungal strains. The high discriminatory potential of this method is particularly useful when dealing with closely related or cryptic species. In the present study, the application of PCR fingerprinting was performed using the micro satellite primer M13 for the purpose of species identification and strain typing of 84 Phaeomoniella -like isolates collected from grapevines with typical symptoms of dieback. The bands produced by MSP-PCR profiles divided the strains into 3 clusters and 5 singletons with a reproducibility level of 80%. Representative isolates from each group and, when possible, isolates from Eutypa dieback and esca symptoms were selected for sequencing of the ITS region. The ITS sequences for the 16 isolates selected from the MSP-PCR profiles were combined and aligned with sequences of 18 isolates retrieved from GenBank, representing a selection of all known Phaeomoniella species. DNA sequences were compared with those available in GenBank using Neighbor-joining (NJ) and Maximum-parsimony (MP) analyses. The phylogenetic trees of the ITS region revealed that the Phaeomoniella isolates clustered with Phaeomoniella chlamydospora reference sequences with a bootstrap support of 100 %. The complexity of the pathosystems vine-trunk diseases shows clearly the need to identify unambiguously the fungal component in order to allow a better understanding of the etiology of these diseases and justify the establishment of control strategies against these fungal agents.

Keywords: Genotyping, MSP-PCR, ITS, phylogeny, trunk diseases

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Authors: Punit Gandhi, J. C. Brezet, Tim Gorter, Uchechi Obinna

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This paper introduces how weather forecasting could help in more efficient energy management for smart homes with the use of Home Energy Management Systems (HEMS). The paper also focuses on educating consumers and helping them make more informed decisions while using the HEMS. A combined approach of technical and user perspective has been selected to develop a novel HEMS-product-service combination in a more comprehensive manner. The current HEMS switches on/off the energy intensive appliances based on the fluctuating electricity tariffs, but with weather forecasting, it is possible to shift the time of use of energy intensive appliances to maximum electricity production from the renewable energy system installed in the house. Also, it is possible to estimate the heating/cooling load of the house for the day ahead demand. Hence, relevant insight is gained in the expected energy production and consumption load for the next day, facilitating better (more efficient, peak shaved, cheaper, etc.) energy management practices for smart homes. In literature, on the user perspective, it has been observed that consumers lose interest in using HEMS after three to four months. Therefore, to further help in better energy management practices, the new system had to be designed in a way that consumers would sustain their interaction with the system on a structural basis. It is hypothesized that, if consumers feel more comfortable with using such system, it would lead to a prolonged usage, including more energy savings and hence financial savings. To test the hypothesis, a survey for the HEMS is conducted, to which 59 valid responses were recorded. Analysis of the survey helped in designing a system which imparts better information about the energy production and consumption to the consumers. It is also found from the survey that, consumers like a variety of options and they do not like a constant reminder of what they should do. Hence, the final system is designed to encourage consumers to make an informed decision about their energy usage with a wide variety of behavioral options available. It is envisaged that the new system will be tested in several pioneering smart energy grid projects in both the Netherlands and India, with a continued ‘design thinking’ approach, combining the technical and user perspective, as the basis for further improvements.

Keywords: weather forecasting, smart grid, renewable energy forecasting, user defined HEMS

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Authors: Menna Ewida, Dalal Abou El-Ella, Dina Lasheen, Huessin El-Subbagh

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Introduction: Vascular Endothelial Growth Factor receptor (VEGF) is a signal protein produced by cells that stimulates vasculogenesis to create new blood vessels. VEGF family binds to three trans-membrane tyrosine kinase receptors,Dihydrofolate reductase (DHFR) is an enzyme of crucial importance in medicinal chemistry. DHFR catalyzes the reduction 7,8 dihydro-folate to tetrahydrofolate and intimately couples with thymidylate synthase which is a pivotal enzyme that catalysis the reductive methylation of deoxyuridine monophosphate (dUMP) to deoxythymidine monophosphate (dTMP) utilizing N5,N10-methylene tetrahydrofolate as a cofactor which functions as the source of the methyl group. Purpose: Novel substituted Thiazole agents were designed as DHFR and VEGF-TK inhibitors with increased synergistic activity and decreased side effects. Methods: Five series of compounds were designed with a rational that mimic the pharmacophoric features present in the reported active compounds that target DHFR & VEGFR. These molecules were docked against Methotrexate & Sorafenib as controls. An in silico ADMET study was also performed to validate the bioavailability of the newly designed compounds. The in silico molecular docking & ADMET study were also applied to the non-classical antifolates for comparison. The interaction energy comparable to that of MTX for DHFRI and Sorafenib for VEGF-TKI activity were recorded. Results: Compound 5 exhibited the highest interaction energy when docked against Sorafenib, While Compound 9 showed the highest interaction energy when docked against MTX with the perfect binding mode. Comparable results were also obtained for the ADMET study. Most of the compounds showed absorption within (95-99) zone which varies according to the type of substituents. Conclusions: The Substituted Thiazole Analogues could be a suitable template for antitumor drugs that possess enhanced bioavailability and act as DHFR and VEGF-TK inhibitors.

Keywords: anti-tumor agents, DHFR, drug design, molecular modeling, VEGFR-TKIs

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Authors: Valeria Arcucci, Musarat Ishaq, Steven A. Stacker, Greg J. Goodall, Marc G. Achen

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Metastasis is the lethal aspect of cancer for most patients. Remodelling of lymphatic vessels associated with a tumour is a key initial step in metastasis because it facilitates the entry of cancer cells into the lymphatic vasculature and their spread to lymph nodes and distant organs. Although it is clear that vascular endothelial growth factors (VEGFs), such as VEGF-C and VEGF-D, are key drivers of lymphatic remodelling, the means by which many signaling pathways in endothelial cells are coordinately regulated to drive growth and remodelling of lymphatics in cancer is not understood. We seek to understand the broader molecular mechanisms that control cancer metastasis, and are focusing on microRNAs, which coordinately regulate signaling pathways involved in complex biological responses in health and disease. Here, using small RNA sequencing, we found that a specific microRNA, miR-132, is upregulated in expression in lymphatic endothelial cells (LECs) in response to the lymphangiogenic growth factors. Interestingly, ectopic expression of miR-132 in LECs in vitro stimulated proliferation and tube formation of these cells. Moreover, miR-132 is expressed in lymphatic vessels of a subset of human breast tumours which were previously found to express high levels of VEGF-D by immunohistochemical analysis on tumour tissue microarrays. In order to dissect the complexity of regulation by miR-132 in lymphatic biology, we performed Argonaute HITS-CLIP, which led us to identify the miR-132-mRNA interactome in LECs. We found that this microRNA in LECs is involved in the control of many different pathways mainly involved in cell proliferation and regulation of the extracellular matrix and cell-cell junctions. We are now exploring the functional significance of miR-132 targets in the biology of LECs using biochemical techniques, functional in vitro cell assays and in vivo lymphangiogenesis assays. This project will ultimately define the molecular regulation of lymphatic remodelling by miR-132, and thereby identify potential therapeutic targets for drugs designed to restrict the growth and remodelling of tumour lymphatics resulting in metastatic spread.

Keywords: argonaute HITS-CLIP, cancer, lymphatic remodelling, miR-132, VEGF

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Authors: Eman M. Sarhan, Doaa A. Ghareeb, Gabriella Ortore, Amr A. Amara, Mohamed M. El-Sayed

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Drug salting and nanoparticle-based drug delivery formulations are considered to be an effective means for rendering the hydrophobic drugs’ nano-scale dispersion in aqueous media, and thus circumventing the pitfalls of their poor solubility as well as enhancing their membrane permeability. The current study aims to increase the bioavailability of quaternary ammonium berberine through acid salting and biodegradable bovine serum albumin (BSA)-based nanoparticulate drug formulation. Berberine hydroxide (BBR-OH) that was chemically synthesized by alkalization of the commercially available berberine hydrochloride (BBR-HCl) was then acidified to get Di-berberine sulfate (BBR)₂SO₄. The purified crystals were spectrally characterized. The desolvation technique was optimized for the preparation of size-controlled BSA-BBR-HCl, BSA-BBR-OH, and BSA-(BBR)₂SO₄ nanoparticles. Particle size, zeta potential, drug release, encapsulation efficiency, Fourier transform infrared spectroscopy (FTIR), tandem MS-MS spectroscopy, energy-dispersive X-ray spectroscopy (EDX), scanning and transmitting electron microscopic examination (SEM, TEM), in vitro bioactivity, and in silico drug-polymer interaction were determined. BSA (PDB ID; 4OR0) protonation state at different pH values was predicted using Amber12 molecular dynamic simulation. Then blind docking was performed using Lamarkian genetic algorithm (LGA) through AutoDock4.2 software. Results proved the purity and the size-controlled synthesis of berberine-BSA-nanoparticles. The possible binding poses, hydrophobic and hydrophilic interactions of berberine on BSA at different pH values were predicted. Antioxidant, anti-hemolytic, and cell differentiated ability of tested drugs and their nano-formulations were evaluated. Thus, drug salting and the potentially effective albumin berberine nanoparticle formulations can be successfully developed using a well-optimized desolvation technique and exhibiting better in vitro cellular bioavailability.

Keywords: berberine, BSA, BBR-OH, BBR-HCl, BSA-BBR-HCl, BSA-BBR-OH, (BBR)₂SO₄, BSA-(BBR)₂SO₄, FTIR, AutoDock4.2 Software, Lamarkian genetic algorithm, SEM, TEM, EDX

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Authors: Satoshi Nishimura

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Although much information has been garnered from the genomes of humans and mice, it remains difficult to extend that information to explain physiological and pathological phenomena. This is because the processes underlying life are by nature stochastic and fluctuate with time. Thus, we developed novel "in vivo molecular imaging" method based on single and two-photon microscopy. We visualized and analyzed many life phenomena, including common adult diseases. We integrated the knowledge obtained, and established new models that will serve as the basis for new minimally invasive therapeutic approaches.

Keywords: two photon microscope, intravital visualization, thrombus, artery

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Authors: Ahmad Fakhriy Hassan, Rohani Ahmad, Zurainee Mohamed Nor, Wan Najdah Wan Mohamad Ali

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In Malaysia, it was realized that while the incidence of human malaria is decreasing, the incidence of Plasmodium knowlesi malaria appears to be on the rise, especially in rural areas of Sabah, East Malaysia. The primary vector for P. knowlesi malaria in Sabah is An. balabacensis a species found abundant in rural areas, shown to rest and feed outdoor throughout the night, which makes its control very challenging. This study aims to examine the distribution of malaria-infected Anopheles mosquitoes in three areas in Sabah, namely Kudat, Ranau, and Tenom, known as areas in Sabah that presented high number of malaria cases. Briefly, mosquitoes were caught every 6 weeks for the period of 18 months using Human Landing Catching (HLC) technique from May 2016 to November 2017. Identification of species was done using microscopy and molecular methods. Molecular method is also used to detect malaria parasite in all mosquito collected. An. balabacensis was present in all the study areas. In Kudat, six other Anopheles species were also detected, namely, An. barumbrosus, An. latens, An. letifer, An. maculatus, An. sundaicus and An. tesselatus. In Ranau five other Anopheles species were detected, namely, An. barumbrosus, An. donaldi., An. hodgkini, An. maculatus, and An. tesselatus while in Tenom seven more species An. donaldi, An. umbrosus, An. barumbrosus, An.latens, An. hodgkini, An. maculatus, and An. tesselatus were detected. This study showed 24% out of 259, 39% out of 127, and 26% out of 265 Anopheles mosquito collected in Kudat, Ranau, and Tenom were detected positive for malaria parasite respectively. In Kudat An. balabacensis, An. barumbrosus, An. latens, An. maculatus, An. sundaicus and An. tesselatus were the six out of eight Anopheles species that were found infected with malaria parasite. All Anopheles species collected in Ranau were positive for malaria while In Tenom, only five out of eight species; An. balabacensus, An. donaldi, An. hodgkini, An. maculatus, and An. latens were detected positive for malaria parasite. Interestingly, for all study areas An. balabacensis was shown to be the only species infected with four malaria species; P. falciparum, P. knowlesi, P. vivax, and Plasmodium sp. This finding clearly indicates that An. balabacensis is the dominant malaria vector in Kudat, Ranau, and Tenom.

Keywords: Anopheles balabacensis, human landing catching technique, nested PCR, Plasmodium knowlesi, Simian malaria

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Authors: Hao-Wen Chang, Santhanamoorthi Nachimuthu, Jyh-Chiang Jiang

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All-solid-state lithium batteries (ASSLBs) are increasingly recognized as a safer and more reliable alternative to conventional lithium-ion batteries due to their non-flammable nature and enhanced safety performance. ASSLBs utilize a range of solid-state electrolytes, including solid polymer electrolytes (SPEs), inorganic solid electrolytes (ISEs), and composite polymer electrolytes (CPEs). SPEs are particularly valued for their flexibility, ease of processing, and excellent interfacial compatibility with electrodes, though their ionic conductivity remains a significant limitation. ISEs, on the other hand, provide high ionic conductivity, broad electrochemical windows, and strong mechanical properties but often face poor interfacial contact with electrodes, impeding performance. CPEs, which merge the strengths of SPEs and ISEs, represent a compelling solution for next-generation ASSLBs by addressing both electrochemical and mechanical challenges. Despite their potential, the mechanisms governing lithium-ion transport within these systems remain insufficiently understood. In this study, we designed CPEs based on argyrodite-type Li₆PS₅Cl (LPSC) combined with two distinct polymer matrices: poly(ethylene oxide) (PEO) with 24.5 wt% lithium bis(trifluoromethane)sulfonimide (LiTFSI) and polycaprolactone (PCL) with 25.7 wt% LiTFSI. Through density functional theory (DFT) calculations, we investigated the interfacial chemistry of these materials, revealing critical insights into their stability and interactions. Additionally, ab initio molecular dynamics (AIMD) simulations of lithium electrodes interfaced with LPSC layers containing polymers and LiTFSI demonstrated that the polymer matrix significantly mitigates LPSC decomposition, compared to systems with only a lithium electrode and LPSC layers. These findings underscore the pivotal role of CPEs in improving the performance and longevity of ASSLBs, offering a promising path forward for next-generation energy storage technologies.

Keywords: all-solid-state lithium-ion batteries, composite solid electrolytes, DFT calculations, Li-ion transport

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Authors: Meltem Betül Sağlam, Halil İbrahim Güler, Aykut Sağlam

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In this work, phthalocyanine compounds containing α-naphtholbenzeinunits have been synthesized. Mutagenicity and DNA binding properties of the compounds were investigated by Salmonella/Microsome Assay and spectrophotometer. According to the results of the preliminary range finding tests, the compounds gave no toxic effect to all tester strain S. typhimurium TA98 and TA100 at doses of 500, 1100, 350, 500 and 750 µg/plate in the presence and absence of S9, respectively. This study showed that all compounds exhibited efficient DNA-binding activity. In conclusion, these non-toxic compounds may be used as effective DNA dyes for molecular biology studies.

Keywords: dye, mutagenicity, phthalocyanine, toxicity

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Authors: Ali Bahkali, Rayan Yousef Booq, Mohammad Khiyami

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Soil samples were collected from five different regions in the Kingdom of Saudi Arabia. Microbiological methods included dilution methods and pour plates to isolate and purify bacteria soil. The ability of isolates to develop biopolymer was investigated on petri dishes containing elements and substance concentrations stimulating developing biopolymer. Fluorescent stains, Nile red and Nile blue were used to stain the bacterial cells developing biopolymers. In addition, Sudan black was used to detect biopolymers in bacterial cells. The isolates which developed biopolymers were identified based on their gene sequence of 1 6sRNA and their ability to grow and synthesize PHAs on mineral medium supplemented with 1% dates molasses as the only carbon source under nitrogen limitation. During the study 293 bacterial isolates were isolated and detected. Through the initial survey on the petri dishes, 84 isolates showed the ability to develop biopolymers. These bacterial colonies developed a pink color due to accumulation of the biopolymers in the cells. Twenty-three isolates were able to grow on dates molasses, three strains of which showed the ability to accumulate biopolymers. These strains included Bacillus sp., Ralstonia sp. and Microbacterium sp. They were detected by Nile blue A stain with fluorescence microscopy (OLYMPUS IX 51). Among the isolated strains Ralstonia sp. was selected after its ability to grow on molasses dates in the presence of a limited nitrogen source was detected. The optimum conditions for formation of biopolymers by isolated strains were investigated. Conditions studied included, best incubation duration (2 days), temperature (30°C) and pH (7-8). The maximum PHB production was raised by 1% (v1v) when using concentrations of dates molasses 1, 2, 3, 4 and 5% in MSM. The best inoculated with 1% old inoculum (1= OD). The ideal extraction method of PHA and PHB proved to be 0.4% sodium hypochlorite solution, producing a quantity of polymer 98.79% of the cell's dry weight. The maximum PHB production was 1.79 g/L recorded by Ralstonia sp. after 48 h, while it was 1.40 g/L produced by R.eutropha ATCC 17697 after 48 h.

Keywords: bacteria forming polyhydroxyalkanoate, detection, molecular, Saudi Arabia

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Authors: Shiraz M. Mammadov, Elvin M. Aliyev, Adil A. Garibov

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The role of the disulfochloride benzene in unsaturated rubbers (SKIN, SKN-26) which is in the systems of SKIN+disulfochloride benzene and SKN-26+disulfochloride benzene was studied by the radiation exposure. By the usage of physical, chemical and spectral methods the changes in the molecular structure of the rubber were shown after irradiation by y-rays at 300 kGy. The outputs and the emergence of the crosslinking in the elastomers for each system depending on absorbed dose were defined. It is suggested that the mechanism of radiation occurs by the heterogeneous transformation of elastomers in the presence of disulfochloride benzene.

Keywords: acrylonitrile-butadiene rubber, crosslinking, polyfunctional monomers, radiation, sensitizier, vulcanization

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Authors: K. Szymkowska, K. Mojsiewicz- Pieńkowska

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Siloxanes are a common ingredients in medicinal products used on the skin, as well as cosmetics. It is widely believed that the silicones are not capable of overcoming the skin barrier. The aim of the study was to verify the possibility of penetration and permeation of linear siloxanes through human skin and determine depth penetration limit of these compounds. Based on the results it was found that human skin is not a barrier for linear siloxanes. PDMS 50 cSt was not identified in the dermis suggests that this molecular size of silicones (3780Da) is safe when it is used in the skin formulations.

Keywords: linear siloxanes, methyl siloxanes, skin penetration, skin permeation

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Authors: Salina Yahya Saddick

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Ovarian cancer remains the most lethal gynecological malignancy due to the lack of highly sensitive and specific screening tools for detection of early-stage disease. The OSE provides the progenitor cells for 90% of human ovarian cancers. Recent morphologic, immunohistochemical and molecular genetic studies have led to the development of a new paradigm for the pathogenesis and origin of epithelial ovarian cancer (EOC) based on a ualistic model of carcinogenesis that divides EOC into two broad categories designated Types I and II which are characterized by specific mutations, including KRAS, BRAF, ERBB2, CTNNB1, PTEN PIK3CA, ARID1A, and PPPR1A, which target specific cell signaling pathways. Type 1 tumors rarely harbor TP53. type I tumors are relatively genetically stable and typically display a variety of somatic sequence mutations that include KRAS, BRAF, PTEN, PIK3CA CTNNB1 (the gene encoding beta catenin), ARID1A and PPP2R1A but very rarely TP53 . The cancer stem cell (CSC) hypothesis postulates that the tumorigenic potential of CSCs is confined to a very small subset of tumor cells and is defined by their ability to self-renew and differentiate leading to the formation of a tumor mass. Potential protein biomarker miRNA, are promising biomarkers as they are remarkably stable to allow isolation and analysis from tissues and from blood in which they can be found as free circulating nucleic acids and in mononuclear cells. Recently, genomic anaylsis have identified biomarkers and potential therapeutic targets for ovarian cancer namely, FGF18 which plays an active role in controlling migration, invasion, and tumorigenicity of ovarian cancer cells through NF-κB activation, which increased the production of oncogenic cytokines and chemokines. This review summarizes update information on epithelial ovarian cancers and point out to the most recent ongoing research.

Keywords: epithelial ovarian cancers, somatic sequence mutations, cancer stem cell (CSC), potential protein, biomarker, genomic analysis, FGF18 biomarker

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Authors: Shih Yu Pan, Pao Chen Hung, Chuan Yao Lin, Charles C.-K. Chou, Yu Chi Lin, Kai Hsien Chi

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This study analyzed 16 atmospheric PAHs species which were controlled by USEPA and IARC. To measure the concentration of PAHs, four rural sampling sites and two urban sampling sites were selected in Central Taiwan during spring and summer. In central Taiwan, the rural sampling stations were located in the downstream of Da-An River, Da-Jang River, Wu River and Chuo-shui River. On the other hand, the urban sampling sites were located in Taichung district and close to the roadside. Ambient air samples of both vapor phase and particle phase of PAHs compounds were collected using high volume sampling trains (Analitica). The sampling media were polyurethane foam (PUF) with XAD2 and quartz fiber filters. Diagnostic ratio, Principal component analysis (PCA), Positive Matrix Factorization (PMF) models were used to evaluate the apportionment of PAHs in the atmosphere and speculate the relative contribution of various emission sources. Because of the high temperature and low wind speed, high PAHs concentration in the atmosphere was observed. The total PAHs concentration, especially in vapor phase, had significant change during summer. During the sampling periods the total PAHs concentration of atmospheric at four rural and two urban sampling sites in spring and summer were 3.70±0.40 ng/m3,3.40±0.63 ng/m3,5.22±1.24 ng/m3,7.23±0.37 ng/m3,7.46±2.36 ng/m3,6.21±0.55 ng/m3　; 15.0± 0.14 ng/m3,18.8±8.05 ng/m3,20.2±8.58 ng/m3,16.1±3.75 ng/m3,29.8±10.4 ng/m3,35.3±11.8 ng/m3, respectively. In order to identify PAHs sources, we used diagnostic ratio to classify the emission sources. The potential sources were diesel combustion and gasoline combustion in spring and summer, respectively. According to the principal component analysis (PCA), the PC1 and PC2 had 23.8%, 20.4% variance and 21.3%, 17.1% variance in spring and summer, respectively. Especially high molecular weight PAHs (BaP, IND, BghiP, Flu, Phe, Flt, Pyr) were dominated in spring when low molecular weight PAHs (AcPy, Ant, Acp, Flu) because of the dominating high temperatures were dominated in the summer. Analysis by using PMF model found the sources of PAHs in spring were stationary sources (34%), vehicle emissions (24%), coal combustion (23%) and petrochemical fuel gas (19%), while in summer the emission sources were petrochemical fuel gas (34%), the natural environment of volatile organic compounds (29%), coal combustion (19%) and stationary sources (18%).

Keywords: PAHs, source identification, diagnostic ratio, principal component analysis, positive matrix factorization

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Authors: Diptoshi Roy, G. Sreevidya Varma, S. Asokan, Chandasree Das

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Germanium Telluride based quaternary thin film switching devices with composition Ge₁₅In₅Te₅₆Ag_24, have been deposited in sandwich geometry on glass substrate with aluminum as top and bottom electrodes. The bulk glassy form of the said composition is prepared by melt quenching technique. In this technique, appropriate quantity of elements with high purity are taken in a quartz ampoule and sealed under a vacuum of 10^-5 mbar. Then, it is allowed to rotate in a horizontal rotary furnace for 36 hours to ensure homogeneity of the melt. After that, the ampoule is quenched into a mixture of ice - water and NaOH to get the bulk ingot of the sample. The sample is then coated on a glass substrate using flash evaporation technique at a vacuum level of 10^-6 mbar. The XRD report reveals the amorphous nature of the thin film sample and Energy - Dispersive X-ray Analysis (EDAX) confirms that the film retains the same chemical composition as that of the base sample. Electrical switching behavior of the device is studied with the help of Keithley (2410^c) source-measure unit interfaced with Lab VIEW 7 (National Instruments). Switching studies, mainly SET (changing the state of the material from amorphous to crystalline) operation is conducted on the thin film form of the sample. This device is found to manifest memory switching as the device remains 'ON' even after the removal of the electric field. Also it is found that amorphous Ge₁₅In₅Te₅₆Ag₂₄ thin film unveils clean memory type of electrical switching behavior which can be justified by the absence of fluctuation in the I-V characteristics. The I-V characteristic also reveals that the switching is faster in this sample as no data points could be seen in the negative resistance region during the transition to on state and this leads to the conclusion of fast phase change during SET process. Scanning Electron Microscopy (SEM) studies are performed on the chosen sample to study the structural changes at the time of switching. SEM studies on the switched Ge₁₅In₅Te₅₆Ag₂₄ sample has shown some morphological changes at the place of switching wherein it can be explained that a conducting crystalline channel is formed in the device when the device switches from high resistance to low resistance state. From these studies it can be concluded that the material may find its application in fast switching Non-Volatile Phase Change Memory (PCM) Devices.

Keywords: Chalcogenides, Vapor deposition, Electrical switching, PCM.

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Authors: Fatima Benchikh-Amiraa, Hocine Laouerb, Smain Amiraa, Guido Flaminic

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The essential oils of the aerial parts of Lavandula multifida and L. stoechas were extracted at the full bloom stage by hydrodistillation and theirs chemical compositions were estimated by means of gas chromatography–mass spectrometry (GC–MS). A total of 46 and 67 constituents were identified representing 95.5% and 98.2% of the total oils, respectively. The main components of L. multifida oil were carvacrol (63.8%), beta-bisabolene (8.7%), spathulenol (6.2%), caryophyllene oxide (3.6%) and linalool (2.9%). The oil of L. stoechas was dominated by fenchone (63.9%), camphor (7.8%), 1,8-cineole (5.3%) and myrtenyl acetate (4.2).

Keywords: essential oils, Lavandula multifida, Lavandula stoechas, chemical and molecular engineering

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Authors: Stefanie Ficht, Lukas Schübel, Magdalena Kleybolte, Markus Eblenkamp, Jana Steger, Dirk Wilhelm, Petra Mela

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Although 3D printing as transformative technology has become of increasing interest in the medical field and the demand for biodegradable polymers has developed to a considerable extent, there are only a few additively manufactured, biodegradable implants on the market. Additionally, the sterilization of such implants and its side effects on degradation have still not been sufficiently studied. Within this work, thermosensitive poly p-dioxanone (PPDO) samples were printed with fused filament fabrication (FFF) and investigated. Subsequently, H₂O₂ plasma and gamma radiation were used as low-temperature sterilization techniques and compared among each other and the control group (no sterilization). In order to assess the effect of different sterilization on the degradation behavior of PPDO, the samples were immersed in phosphate-buffered solution (PBS) over 28 days, and surface morphology, thermal properties, molecular weight, inherent viscosity, and mechanical properties were examined at regular time intervals. The study demonstrates that PPDO was printed with great success and that thermal properties, molecular weight (Mw), and inherent viscosity (IV) were not significantly affected by the printing process itself. H₂O₂ plasma sterilization did not significantly harm the thermosensitive polymer, while gamma radiation lowered IV and Mw statistically significantly compared to the control group (p < 0.001). During immersion in PBS, a decrease in Mw and mechanical strength occurred for all samples. However, gamma sterilized samples were affected to a much higher extent compared to the two other sample groups both in final values and timeline. This was confirmed by scanning electron microscopy showing no changes of surface morphology of (non-sterilized) control samples, first microcracks appearing on plasma sterilized samples after two weeks while being present on gamma sterilized samples already immediately after radiation to then further deteriorate over immersion duration. To conclude, we demonstrated that FFF and H₂O₂ plasma sterilization are well suited for processing thermosensitive, biodegradable polymers used for the development of innovative short-term medical applications.

Keywords: additive manufacturing, sterilization, biodegradable, thermosensitive, medical application

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Authors: Jong Il Rhee

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The polypeptide representing the mature part of human BMP-7 was cloned and efficiently expressed in Escherichia coli and Bacillus subtilis, which had a clear band for hBMP-7, a homodimeric protein with an apparent molecular weight of 15.4 kDa. Recombinant E.coli produced 111 pg hBMP-7/mg of protein hBMP-7 through IPTG induction. Recombinant B. subtilis also produced 350 pg hBMP-7/ml of culture medium. The hBMP-7 was purified in 2 steps using an FPLC system with an ion exchange column and a gel filtration column. The hBMP-7 produced in this work also stimulated the alkaline phosphatase (ALP) activity in a dose-dependent manner, i.e. 2.5- and 8.9-fold at 100 and 300 ng hBMP-7/ml, respectively, and showed intact biological activity.

Keywords: B. subtilis, E. coli, fermentation, hBMP-7

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Authors: Anitha Kandasamy, Thirumurugan Ramaiah

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Interestingly, organic materials exhibit large optical nonlinearity with quick responses and having the flexibility of molecular tailoring using computational modelling and favourable synthetic methodologies. Pyridine based organic compounds and carboxylic acid contained aromatic compounds play a crucial role in crystal engineering of NCS complexes that displays admirable optical nonlinearity with fast response and favourable physicochemical properties such as low dielectric constant, wide optical transparency and large laser damage threshold value requires for optoelectronics device applications. Based on these facts, it was projected to form an acentric molecule of π-conjugated system interaction with appropriately replaced electron donor and acceptor groups for achieving higher SHG activity in which quinoline-2-carboyxlic acid is chosen as an electron acceptor and capable of acting as an acid as well as a base molecule, while 2-amino-4-methylpyridine is used as an electron donor and previously employed in numerous proton transfer complexes for synthesis of NLO materials for optoelectronic applications. 2-amino-4-mehtylpyridinium quinoline-2-carboxylate molecular complex (2AQ) is having π-donor-acceptor groups in which 2-amino-4-methylpyridine donates one of its electron to quinoline -2-carboxylic acid thereby forming a protonated 2-amino-4-methyl pyridinium moiety and mono ionized quinoline-2-carboxylate moiety which are connected via N-H…O intermolecular interactions with non-centrosymmetric crystal packing arrangement at microscopic scale is accountable to the enhancement of macroscopic second order NLO activity. The 2AQ crystal was successfully grown by a slow evaporation solution growth technique and its structure was determined in orthorhombic crystal system with acentric, P212121, space group. Hirshfeld surface analysis reveals that O…H intermolecular interactions primarily contributed with 31.0 % to the structural stabilization of 2AQ. The molecular structure of title compound has been confirmed by 1H and 13C NMR spectral studies. The vibrational modes of functional groups present in 2AQ have been assigned by using FTIR and FT-Raman spectroscopy. The grown 2AQ crystal exhibits high optical transparency with lower cut-off wavelength (275 nm) within the region of 275-1500 nm. The laser study confirmed that 2AQ exhibits high SHG efficiency of 12.6 times greater than that of KDP. TGA-DTA analysis revealed that 2AQ crystal had a thermal stability of 223 °C. The low dielectric constant and low dielectric loss at higher frequencies confirmed good crystalline nature with fewer defects of grown 2AQ crystal. The grown crystal exhibits soft material and positive photoconduction behaviour. Mulliken atomic distribution and FMOs analysis suggested that the strong intermolecular hydrogen bonding which lead to the enhancement of NLO activity. These properties suggest that 2AQ crystal is a suitable material for optoelectronic and laser frequency conversion applications.

Keywords: crystal growth, NLO activity, proton transfer complex, quantum chemical investigation

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Authors: Don Anushka Sandaruwan Elvitigala, P. D. S. U. Wickramasinghe, Jehee Lee

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Cystatins are a large superfamily of proteins which act as reversible inhibitors of cysteine proteases. Papain proteases and cysteine cathepsins are predominant substrates of cystatins. Cystatin superfamily can be further clustered into three groups as Stefins, Cystatins, and Kininogens. Among them, stefines are also known as family 1 cystatins which harbors cystatin Bs and cystatin As. In this study, a homologue of family one cystatins more close to cystatin Bs was identified from Korean black rockfish (Sebastes schlegeli) using a prior constructed cDNA (complementary deoxyribonucleic acid) database and designated as RfCyt1. The full-length cDNA of RfCyt1 consisted of 573 bp, with a coding region of 294 bp. It comprised a 5´-untranslated region (UTR) of 55 bp, and 3´-UTR of 263 bp. The coding sequence encodes a polypeptide consisting of 97 amino acids with a predicted molecular weight of 11kDa and theoretical isoelectric point of 6.3. The RfCyt1 shared homology with other teleosts and vertebrate species and consisted conserved features of cystatin family signature including single cystatin-like domain, cysteine protease inhibitory signature of pentapeptide (QXVXG) consensus sequence and N-terminal two conserved neighboring glycine (⁸GG⁹) residues. As expected, phylogenetic reconstruction developed using the neighbor-joining method showed that RfCyt1 is clustered with the cystatin family 1 members, in which more closely with its teleostan orthologues. An SYBR Green qPCR (quantitative polymerase chain reaction) assay was performed to quantify the RfCytB transcripts in different tissues in healthy and immune stimulated fish. RfCyt1 was ubiquitously expressed in all tissue types of healthy animals with gill and spleen being the highest. Temporal expression of RfCyt1 displayed significant up-regulation upon infection with Aeromonas salmonicida. Recombinantly expressed RfCyt1 showed concentration-dependent papain inhibitory activity. Collectively these findings evidence for detectable protease inhibitory and immunity relevant roles of RfCyt1 in Sebastes schlegeli.

Keywords: Sebastes schlegeli, family 1 cystatin, immune stimulation, expressional modulation

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Authors: Mateen A Khan, Taj Mohammad, Md. Imtaiyaz Hassan

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Alzheimer’s disease is characterized by the accumulation of the processing products of the amyloid beta peptide cleaved by amyloid precursor protein (APP). Iron increases the synthesis of amyloid beta peptides, which is why iron is present in Alzheimer's disease patients' amyloid plaques. Iron misregulation in the brain is linked to the overexpression of APP protein, which is directly related to amyloid-β aggregation in Alzheimer’s disease. The APP 5'-UTR region encodes a functional iron-responsive element (IRE) stem-loop that represents a potential target for modulating amyloid production. Targeted regulation of APP gene expression through the modulation of 5’-UTR sequence function represents a novel approach for the potential treatment of AD because altering APP translation can be used to improve both the protective brain iron balance and provide anti-amyloid efficacy. The molecular docking analysis of APP IRE RNA with eukaryotic translation initiation factors yields several models exhibiting substantial binding affinity. The finding revealed that the interaction involved a set of functionally active residues within the binding sites of eIF4F. Notably, APP IRE RNA and eIF4F interaction were stabilized by multiple hydrogen bonds with residues of APP IRE RNA and eIF4F. It was evident that APP IRE RNA exhibited a structural complementarity that tightly fit within binding pockets of eIF4F. The simulation studies further revealed the stability of the complexes formed between RNA and eIF4F, which is crucial for assessing the strength of these interactions and subsequent roles in the pathophysiology of Alzheimer’s disease. In addition, MD simulations would capture conformational changes in the IRE RNA and protein molecules during their interactions, illustrating the mechanism of interaction, conformational change, and unbinding events and how it may affect aggregation propensity and subsequent therapeutic implications. Our binding studies correlated well with the translation efficiency of APP mRNA. Overall, the outcome of this study suggests that the genomic modification and/or inhibiting the expression of amyloid protein by targeting APP IRE RNA can be a viable strategy to identify potential therapeutic targets for AD and subsequently be exploited for developing novel therapeutic approaches.

Keywords: Alzheimer's disease, Protein-RNA interaction analysis, molecular docking simulations, conformational dynamics, binding stability, binding kinetics, protein synthesis.

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Authors: Gobinathan Devathasan, Kezia Devathasan

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Objective: To improve the current modified Broca-Wernicke-Lichtheim-Kussmaul speech schema and provide insight into autism. Methods: We reviewed the pertinent literature. Current findings, involving Brodmann areas 22, 46, 9,44,45,6,4 are based on neuropathology and functional MRI studies. However, in primary autism, there is no lucid explanation and changes described, whether neuropathology or functional MRI, appear consequential. Findings: We forward an enhanced model which may explain the enigma related to autism. Vowel output is subcortical and does need cortical representation whereas consonant speech is cortical in origin. Left lateralization is needed to commence the circuitry spin as our life have evolved with L-amino acids and left spin of electrons. A fundamental species difference is we are capable of three syllable-consonants and bi-syllable expression whereas cetaceans and songbirds are confined to single or dual consonants. The 4 key sites for speech are superior auditory cortex, Broca’s two areas, and the supplementary motor cortex. Using the Argand’s diagram and Reimann’s projection, we theorize that the Euclidean three dimensional synaptic neuronal circuits of speech are quantized to coherent waves, and then decoherence takes place at area 6 (spherical representation). In this quantum state complex, 3-consonant languages are instantaneously integrated and multiple languages can be learned, verbalized and differentiated. Conclusion: We postulate that evolutionary human speech is elevated to quantum interaction unlike cetaceans and birds to achieve the three consonants/bi-syllable speech. In classical primary autism, the sudden speech switches off and on noted in several cases could now be explained not by any anatomical lesion but failure of coherence. Area 6 projects directly into prefrontal saccadic area (8); and this further explains the second primary feature in autism: lack of eye contact. The third feature which is repetitive finger gestures, located adjacent to the speech/motor areas, are actual attempts to communicate with the autistic child akin to sign language for the deaf.

Keywords: quantum neuronal paradigm, cetaceans and human speech, autism and rapid magnetic stimulation, coherence and decoherence of speech

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Authors: Restu Misrianti

Abstract:

The amino acid variation of Asn (allele A) at position 631 in Mx gene was specific to positive antiviral to avian viral desease. This research was aimed at identifying polymorphism of Mx gene in duck using molecular technique. Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) technique was used to select the genotype of AA, AG and GG. There were thirteen duck from Indragiri Hulu regency (Riau Province) used in this experiment. DNA amplification results showed that the Mx gene in duck is found in a 73 bp fragment. Mx gene in duck did not show any polymorphism. The frequency of the resistant allele (AA) was 0%, while the frequency of the susceptible allele (GG) was 100%.

Keywords: duck, Mx gene, PCR, RFLP

Procedia PDF Downloads 325

Authors: I. Belyamani, M. K. Hassan, J. U. Otaigbe, W. R. Fielding, K. A. Mauritz, J. S. Wiggins, W. L. Jarrett

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We have investigated the flame-retardant efficiency of special new phosphate glass (P-glass) compositions having different glass transition temperatures (Tg) on the processing conditions of polyamide 6,6 (PA6,6) and the final hybrid flame retardancy (FR). We have showed that the low Tg P glass composition (i.e., ILT 1) is a promising flame retardant for PA6,6 at a concentration of up to 15 wt. % compared to intermediate (IIT 3) and high (IHT 1) Tg P glasses. Cone calorimetry data showed that the ILT 1 decreased both the peak heat release rate and the total heat amount released from the PA6,6/ILT 1 hybrids, resulting in an efficient formation of a glassy char layer. These intriguing findings prompted to address several questions concerning the mechanism of action of the different P glasses studied. The general mechanism of action of phosphorous based FR additives occurs during the combustion stage by enhancing the morphology of the char and the thermal shielding effect. However, the present work shows that P glass based FR additives act during melt processing of PA6,6/P glass hybrids. Dynamic mechanical analysis (DMA) revealed that the Tg of PA6,6/ILT 1 was significantly shifted to a lower Tg (~65 oC) and another transition appeared at high temperature (~ 166 oC), thus indicating a strong interaction between PA6,6 and ILT 1. This was supported by a drop in the melting point and crystallinity of the PA6,6/ILT 1 hybrid material as detected by differential scanning calorimetry (DSC). The dielectric spectroscopic investigation of the networks’ molecular level structural variations (i.e. hybrids chain motion, Tg and sub-Tg relaxations) agreed very well with the DMA and DSC findings; it was found that the three different P glass compositions did not show any effect on the PA6,6 sub-Tg relaxations (related to the NH2 and OH chain end groups motions). Nevertheless, contrary to IIT 3 and IHT 1 based hybrids, the PA6,6/ILT 1 hybrid material showed an evidence of splitting the PA6,6 Tg relaxations into two peaks. Finally, the CPMAS 31P-NMR data confirmed the miscibility between ILT 1 and PA6,6 at the molecular level, as a much larger enhancement in cross-polarization for the PA6,6/15%ILT 1 hybrids was observed. It can be concluded that compounding low Tg P-glass (i.e. ILT 1) with PA6,6 facilitates hydrolytic chain scission of the PA6,6 macromolecules through a potential chemical interaction between phosphate and the alpha-Carbon of the amide bonds of the PA6,6, leading to better flame retardant properties.

Keywords: broadband dielectric spectroscopy, composites, flame retardant, polyamide, phosphate glass, sustainable

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Authors: Sayani Chatterjee, Kusum Lata Pangtey, Sarita Singh, Harvir Singh

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Biodegradation leads to a systematic alteration of the chemical and physical properties of crude oil showing sequential depletion of n-alkane, cycloalkanes, aromatic which increases its specific gravity, viscosity and the abundance of heteroatom-containing compounds. The biodegradation leads to a change in the molecular fingerprints and geochemical parameters of degraded oils, thus make source and maturity identification inconclusive or ambiguous. Asphaltene is equivalent to the most labile part of the respective kerogen and generally has high molecular weight. Its complex chemical structure with substantial microporous units makes it suitable to occlude the hydrocarbon expelled from the source. The occluded molecules are well preserved by the macromolecular structure and thus prevented from secondary alterations. They retain primary organic geochemical information over the geological time. The present study involves the extraction of this occluded hydrocarbon from the asphaltene cage through mild oxidative degradation using mild oxidative reagents like Hydrogen Peroxide (H₂O₂) and Acetic Acid (CH₃COOH) on purified asphaltene of the biodegraded oils of Mansa, Lanwa and Santhal fields in Cambay Basin. The study of these extracted occluded hydrocarbons was carried out for establishing oil to oil and oil to source correlation in the Mehsana block of Cambay Basin. The n-alkane and biomarker analysis through GC and GC-MS of these occluded hydrocarbons show similar biomarker imprint as the normal oil in the area and hence correlatable with them. The abundance of C29 steranes, presence of Oleanane, Gammacerane and 4-Methyl sterane depicts that the oils are derived from terrestrial organic matter deposited in the stratified saline water column in the marine environment with moderate maturity (VRc 0.6-0.8). The oil source correlation study suggests that the oils are derived from Jotana-Warosan Low area. The developed geochemical technique to extract the occluded hydrocarbon has effectively resolved the ambiguity that resulted from the inconclusive fingerprint of the biodegraded oil and the method can be also applied in other biodegraded oils as well.

Keywords: asphaltene, biomarkers, correlation, mild oxidation, occluded hydrocarbon

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Authors: Fakhreldin O. Suliman, Alia H. Al-Battashi

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This work explored the interaction of three different imidazoline drugs, naphazoline nitrate (NPH), oxymetazoline hydrochloride (OXY) and xylometazoline hydrochloride (XYL) with two different synthesized cucurbit[n]urils CB[n], cucurbit[7]uril (CB[7]) and cucuribit[8]uril (CB[8]). Three binary inclusion complexes have been investigated in solution and in the solid state. The solid complexes were obtained by lyophilization, whereas the physical mixtures of guests and hosts at a stoichiometric ratio of 1:1 were obtained for each drug. 1HNMR, electrospray ionization mass spectrometry (ESI-MS), and matrix-assisted laser desorption-ionization time-of-flight (MALDI-TOF) mass spectrometry was used to study the complexes prepared in aqueous media. The lyophilized solid complexes were characterized by Fourier transform-infrared spectroscopy (FT-IR), powder X-ray diffractometry (PXRD), thermogravimetric analysis (TGA), and differential scanning calorimetry (DSC). MS, FT-IR and PXRD experimental results established in this work reveal that NPH, OXY and XYL molecules form stable inclusion complexes with the two hosts. The TGA and DSC confirmed the enhancement of the thermal stability of each drug and the production of a thermally stable solid complex. The 1HNMR has shown that the protons of the guests faced shifting in ppm and broadening of their peaks upon the formation of inclusion complexes with the selected CB[n]. The aromatic protons of the guest exhibited the highest changes in the chemical shifts and shape of the NMR peaks, suggesting their inclusion into the cavity of the CB[n]. The diffusion coefficients (D), developed from the diffusion-controlled NMR Spectroscopy (DOSY) measurements, for the complexation of the selected imidazoline drugs with CB[7] and CB[8], were decreased in the presence of hosts compared to the free guests indicating the formation of the guest-host adduct. Furthermore, we conducted molecular dynamic simulations and quantum mechanics calculations on these complexes. The results of the theoretical study corroborate the experimental findings and have also shed light on the mechanism of inclusion of the guests into the two hosts. This study generates initial data for potential drug delivery or drug formulation systems for these three selected imidazoline drug compounds based on their inclusion into the CB[n] cavities.

Keywords: cucurbit[n]urils, imidazoline, inclusion complexes, molecular dynamics, DFT calculations, mass spectrometry

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Authors: Viktor Kochkodan

Abstract:

The main problem arising upon water treatment and desalination using pressure driven membrane processes such as microfiltration, ultrafiltration, nanofiltration and reverse osmosis is membrane fouling that seriously hampers the application of the membrane technologies. One of the main approaches to mitigate membrane fouling is to minimize adhesion interactions between a foulant and a membrane and the surface coating of the membranes with polyelectrolytes seems to be a simple and flexible technique to improve the membrane fouling resistance. In this study composite polyamide membranes NF-90, NF-270, and BW-30 were modified using electrostatic deposition of polyelectrolyte multilayers made from various polycationic and polyanionic polymers of different molecular weights. Different anionic polyelectrolytes such as: poly(sodium 4-styrene sulfonate), poly(vinyl sulfonic acid, sodium salt), poly(4-styrene sulfonic acid-co-maleic acid) sodium salt, poly(acrylic acid) sodium salt (PA) and cationic polyelectrolytes such as poly(diallyldimethylammonium chloride), poly(ethylenimine) and poly(hexamethylene biguanide were used for membrane modification. An effect of deposition time and a number of polyelectrolyte layers on the membrane modification has been evaluated. It was found that degree of membrane modification depends on chemical nature and molecular weight of polyelectrolytes used. The surface morphology of the prepared composite membranes was studied using atomic force microscopy. It was shown that the surface membrane roughness decreases significantly as a number of the polyelectrolyte layers on the membrane surface increases. This smoothening of the membrane surface might contribute to the reduction of membrane fouling as lower roughness most often associated with a decrease in surface fouling. Zeta potentials and water contact angles on the membrane surface before and after modification have also been evaluated to provide addition information regarding membrane fouling issues. It was shown that the surface charge of the membranes modified with polyelectrolytes could be switched between positive and negative after coating with a cationic or an anionic polyelectrolyte. On the other hand, the water contact angle was strongly affected when the outermost polyelectrolyte layer was changed. Finally, a distinct difference in the performance of the noncoated membranes and the polyelectrolyte modified membranes was found during treatment of seawater in the non-continuous regime. A possible mechanism of the higher fouling resistance of the modified membranes has been discussed.

Keywords: contact angle, membrane fouling, polyelectrolytes, surface modification

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Authors: Adriana Haulica

Abstract:

Powered by Machine Learning, Precise medicine is tailored by now to use genetic and molecular profiling, with the aim of optimizing the therapeutic benefits for cohorts of patients. As the majority of Machine Language algorithms come from heuristics, the outputs have contextual validity. This is not very restrictive in the sense that medicine itself is not an exact science. Meanwhile, the progress made in Molecular Biology, Bioinformatics, Computational Biology, and Precise Medicine, correlated with the huge amount of human biology data and the increase in computational power, opens new healthcare challenges. A more accurate diagnosis is needed along with real-time treatments by processing as much as possible from the available information. The purpose of this paper is to present a deeper vision for the future of Artificial Intelligence in Precise medicine. In fact, actual Machine Learning algorithms use standard mathematical knowledge, mostly Euclidian metrics and standard computation rules. The loss of information arising from the classical methods prevents obtaining 100% evidence on the diagnosis process. To overcome these problems, we introduce MEDICOMPILLS, a new architectural concept tool of information processing in Precise medicine that delivers diagnosis and therapy advice. This tool processes poly-field digital resources: global knowledge related to biomedicine in a direct or indirect manner but also technical databases, Natural Language Processing algorithms, and strong class optimization functions. As the name suggests, the heart of this tool is a compiler. The approach is completely new, tailored for omics and clinical data. Firstly, the intrinsic biological intuition is different from the well-known “a needle in a haystack” approach usually used when Machine Learning algorithms have to process differential genomic or molecular data to find biomarkers. Also, even if the input is seized from various types of data, the working engine inside the MEDICOMPILLS does not search for patterns as an integrative tool. This approach deciphers the biological meaning of input data up to the metabolic and physiologic mechanisms, based on a compiler with grammars issued from bio-algebra-inspired mathematics. It translates input data into bio-semantic units with the help of contextual information iteratively until Bio-Logical operations can be performed on the base of the “common denominator “rule. The rigorousness of MEDICOMPILLS comes from the structure of the contextual information on functions, built to be analogous to mathematical “proofs”. The major impact of this architecture is expressed by the high accuracy of the diagnosis. Detected as a multiple conditions diagnostic, constituted by some main diseases along with unhealthy biological states, this format is highly suitable for therapy proposal and disease prevention. The use of MEDICOMPILLS architecture is highly beneficial for the healthcare industry. The expectation is to generate a strategic trend in Precise medicine, making medicine more like an exact science and reducing the considerable risk of errors in diagnostics and therapies. The tool can be used by pharmaceutical laboratories for the discovery of new cures. It will also contribute to better design of clinical trials and speed them up.

Keywords: bio-semantic units, multiple conditions diagnosis, NLP, omics

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