Search results for: genes expression

Authors: Peter Williams

Abstract:

Mobile digital technology, in the form of smart phones, tablets, laptops and their accompanying functionality/apps etc., is becoming ever more used by people with Learning Disabilities (LD) - for entertainment, to communicate and socialize, and enjoy self-expression. Despite this, there has been very little research into the experiences of such technology by this cohort, it’s role in articulating personal identity and self-advocacy and the barriers encountered in negotiating technology in everyday life. The proposed talk describes research funded by the British Academy addressing these issues. It aims to explore: i) the experiences of people with LD in using mobile technology in their everyday lives – the benefits, in terms of entertainment, self-expression and socialising, and possible greater autonomy; and the barriers, such as accessibility or usability issues, privacy or vulnerability concerns etc. ii) how the technology, and in particular the software/apps and interfaces, can be improved to enable the greater access to entertainment, information, communication and other benefits it can offer. It is also hoped that results will inform parents, carers and other supporters regarding how they can use the technology with their charges. Rather than the project simply following the standard research procedure of gathering and analysing ‘data’ to which individual ‘research subjects’ have no access, people with Learning Disabilities (and their supporters) will help co-produce an accessible, annotated and hyperlinked living e-archive of their experiences. Involving people with LD as informants, contributors and, in effect, co-researchers will facilitate digital inclusion and empowerment. The project is working with approximately 80 adults of all ages who have ‘mild’ learning disabilities (people who are able to read basic texts and write simple sentences). A variety of methods is being used. Small groups of participants have engaged in simple discussions or storytelling about some aspect of technology (such as ‘when my phone saved me’ or ‘my digital photos’ etc.). Some individuals have been ‘interviewed’ at a PC, laptop or with a mobile device etc., and asked to demonstrate their usage and interests. Social media users have shown their Facebook pages, Pinterest uploads or other material – giving them an additional focus they have used to discuss their ‘digital’ lives. During these sessions, participants have recorded (or employed the researcher to record) their observations on to the e-archive. Parents, carers and other supporters are also being interviewed to explore their experiences of using mobile technology with the cohort, including any difficulties they have observed their charges having. The archive is supplemented with these observations. The presentation will outline the methods described above, highlighting some of the special considerations required when working inclusively with people with LD. It will describe some of the preliminary findings and demonstrate the e-archive with a commentary on the pages shown.

Keywords: inclusive research, learning disabilities, methods, technology

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Authors: Huai-Feng Wang, Meng-Lin Lou, Ru-Lin Zhang

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One good analysis method in seismic response analysis is direct time integration, which widely adopts Rayleigh damping. An approach is presented for selection of Rayleigh damping coefficients to be used in seismic analyses to produce a response that is consistent with Modal damping response. In the presented approach, the expression of the error of peak response, acquired through complete quadratic combination method, and Rayleigh damping coefficients was set up and then the coefficients were produced by minimizing the error. Two finite element modes of soil layers, excited by 28 seismic waves, were used to demonstrate the feasibility and validity.

Keywords: Rayleigh damping, modal damping, damping coefficients, seismic response analysis

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Authors: Xiran Wang, Johanna Trinkl, Thomas Hoffmann, Wilfried Schwab

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Malonyltransferases (MATs) are enzymes that play a key role in the biosynthesis of secondary metabolites in plants, such as flavonoids and anthocyanins. As a kind of flavonoid-rich fruit, strawberries are an ideal model to study MATs. From Goodberry metabolome data, in the hybrid generation of 2 strawberries various, Fragaria × ananassa cv. 'Senga Sengana' and 'Candonga', we found the malonylated flavonoid concentration is significantly higher in 'Senga Sengana' compared with 'Candonga'. Therefore, we aimed to identify and characterize the malonyltransferases responsible for the different malonylated flavonoid concentrations in two different strawberry cultivars. In this study, we have found 6 MATs via genome mapping, metabolome analysis, gene cloning, and enzyme assay from strawberries, which catalyzed the malonylation of flavonoid substrates: quercetin-3-glucoside, kaempferol-3-glucoside, pelargonidin-3-glucoside, and cyanidin-3-glucoside. All four compounds reacted with FaMATs to varying degrees. These MATs have important implication into strawberries’ flavonoid biosynthesis, and also provide insights into insights into flavonoid biosynthesis, potential applications in agriculture, plant science, and pharmacy, and information on the regulation of secondary metabolism in plants.

Keywords: malonyltransferase, strawberry, flavonoid biosynthesis, enzyme assay

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Authors: Yudi Zhao, Ziyun Zhou, Yueting Yao, Shuying Dai, Zhiling Yan, Longyu Yang, Chuanyin Li, Li Shi, Yufeng Yao

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HPV16 E4 gene plays an important role in viral genome amplification and release. Therefore, a variation of the E4 gene nucleic acid sequence may affect the carcinogenicity of HPV16. In order to understand the relationship between the variation of HPV16 E4 gene and cervical cancer, this study was to amplify and sequence the DNA sequences of E4 genes in 118 HPV16-positive cervical cancer patients and 151 HPV16-positive asymptomatic individuals. After obtaining E4 gene sequences, the phylogenetic trees were constructed by the Neighbor-joining method for gene variation analysis. The results showed that: 1) The distribution of HPV16 variants between the case group and the control group differed greatly (P = 0.015)，and the Asian-American（AA）variant was likely to relate to the occurrence of cervical cancer. 2) DNA sequence analysis showed that there were significant differences in the distribution of 8 variants between the case group and the control group (P < 0.05). And 3) In European (EUR) variant, two variations, C3384T (L18L) and A3449G (P39P), were associated with the initiation and development of cervical cancer. The results suggested that the variation of HPV16 E4 gene may be a contributor affecting the occurrence as well as the development of cervical cancer, and different HPV16 variants may have different carcinogenic capability.

Keywords: cervical cancer, HPV16, E4 gene, variations

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Authors: Xi Chen, King-Yip Cheng

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Hypercholesterolemia, characterized by high low-density lipoprotein cholesterol (LDL-C), raises cardiovascular events in patients with type 2 diabetes (T2D). Although several drugs, such as statin and PCSK9 inhibitors, are available for the treatment of hypercholesterolemia, they exert detrimental effects on glucose metabolism and hence increase the risk of T2D. On the other hand, the drugs used to treat T2D have minimal effect on improving the lipid profile. Therefore, there is an urgent need to develop treatments that can simultaneously improve glucose and lipid homeostasis. Adaptor protein phosphotyrosine interacting with PH domain and leucine zipper 2 (APPL2) causes insulin resistance in the liver and skeletal muscle via inhibiting insulin and adiponectin actions in animal models. Single-nucleotide polymorphisms in the APPL2 gene were associated with LDL-C, non-alcoholic fatty liver disease, and coronary artery disease in humans. The aim of this project is to investigate whether APPL2 antisense oligonucleotide (ASO) can alleviate dietary-induced T2D and hypercholesterolemia. High-fat diet (HFD) was used to induce obesity and insulin resistance in mice. GalNAc-conjugated APPL2 ASO (GalNAc-APPL2-ASO) was used to silence hepatic APPL2 expression in C57/BL6J mice selectively. Glucose, lipid, and energy metabolism were monitored. Immunoblotting and quantitative PCR analysis showed that GalNAc-APPL2-ASO treatment selectively reduced APPL2 expression in the liver instead of other tissues, like adipose tissues, kidneys, muscle, and heart. The glucose tolerance test and insulin sensitivity test revealed that GalNAc-APPL2-ASO improved glucose tolerance and insulin sensitivity progressively. Blood chemistry analysis revealed that the mice treated with GalNAc-APPL2-ASO had significantly lower circulating levels of total cholesterol and LDL cholesterol. However, there was no difference in circulating levels of high-density lipoprotein (HDL) cholesterol, triglyceride, and free fatty acid between the mice treated with GalNac-APPL2-ASO and GalNAc-Control-ASO. No obvious effect on food intake, body weight, and liver injury markers after GalNAc-APPL2-ASO treatment was found, supporting its tolerability and safety. We showed that selectively silencing hepatic APPL2 alleviated insulin resistance and hypercholesterolemia and improved energy metabolism in the dietary-induced obese mouse model, indicating APPL2 as a therapeutic target for metabolic diseases.

Keywords: APPL2, antisense oligonucleotide, hypercholesterolemia, type 2 diabetes

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Authors: Mushtaq Ahmad, Bashir Rahman, Taqweem-ul-Haq, Fazal Jalil, Aftab Ali Shah

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Single nucleotide polymorphisms (SNPs) in genes coding for microRNAs (miRNAs) play a pivotal role in the progression of breast cancer (BC). We investigated the association of miR-146a rs2910164 G/C polymorphism with the risk of BC in the Pakistani population. The miR-146a rs2910164 polymorphism was genotyped in 300 BC-cases and 300 age- and gender-matched healthy controls using T-ARMS-PCR. Genotype and allele frequencies were calculated, and the association between genotypes and the risk of BC was calculated by odds ratios (OR) and confidence intervals (95%). A significant difference in genotypic frequencies (χ2=63.10; p ≤ 0.0001) and allelic frequencies (OR=0.3955 (0.3132-0.4993); p ≤ 0.0001) was observed between cases and controls. Furthermore, we also found that miR-146 rs2910164 CC homozygote increased the risk of breast cancer in the dominant (OR=0.2397 (0.1629-0.3526); p=0.0001; GG vs GC+CC) and recessive (OR=2.803 (1.865- 4.213); P ≤ 0.0001; CC vs GC+GG) inheritance models. In summary, miR-146a rs2910164 G/C is significantly associated with BC in the Pakistani population. To our knowledge, this is the first study that assessed MIR146a rs2910164 G > C SNP in Pakistani population. By analyzing the secondary structure of MIR146A variant, a significant structural modification was noted. Study with a larger sample size is needed to further confirm these findings.

Keywords: breast cancer, MIR146A, microRNA, SNP

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Authors: Paulo Da Silva Quadros

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This work aims to point out comparative parameters between the artistic production of two exponents of the contemporary popular culture scene: Caetano Veloso (Brazil) and David Bowie (England). Both Caetano Veloso and David Bowie were pioneers in establishing an aesthetic game between various artistic expressions at the service of the music-visual scene, that is, the conceptual interconnections between several forms of aesthetic processes, such as fine arts, theatre, cinema, poetry, and literature. There are also correlations in their expressive attitudes of art, especially regarding the dialogue between the fields of art and politics (concern with respect to human rights, human dignity, racial issues, tolerance, gender issues, and sexuality, among others); the constant tension and cunning game between market, free expression and critical sense; the sophisticated, playful mechanisms of metalanguage and aesthetic metacritique. Fact is that both of them almost came to cooperate with each other in the 1970s when Caetano was in exile in England, and when both had at the same time the same music producer, who tried to bring them closer, noticing similar aesthetic qualities in both artistic works, which was later glimpsed by some music critics. Among many of the most influential issues in Caetano's and Bowie's game of artistic-aesthetic expression are, for example, the ideas advocated by the sensation of strangeness (Albert Camus), art as transcendence (Friedrich Nietzsche), the deconstruction and reconstruction of auratic reconfiguration of artistic signs (Walter Benjamin and Andy Warhol). For deepen more theoretical issues, the following authors will be used as supportive interpretative references: Hans-Georg Gadamer, Immanuel Kant, Friedrich Schiller, Johan Huizinga. In addition to the aesthetic meanings of Ars Ludens characteristics of the two artists, the following supporting references will be also added: the question of technique (Martin Heidegger), the logic of sense (Gilles Deleuze), art as an event and the sense of the gesture of art ( Maria Teresa Cruz), the society of spectacle (Guy Debord), Verarbeitung and Durcharbeitung (Sigmund Freud), the poetics of interpretation and the sign of relation (Cremilda Medina). The purpose of such interpretative references is to seek to understand, from a cultural reading perspective (cultural semiology), some significant elements in the dynamics of aesthetic and media interconnections of both artists, which made them as some of the most influential interlocutors in contemporary music aesthetic thought, as a playful vivid experience of life and art.

Keywords: Caetano Veloso, David Bowie, music aesthetics, symbolic playfulness, cultural reading

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Authors: Hae Jeong Park, Joo-Ho Chung

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In this study, the effect of essential oil from Chamaecyparis obtuse (EOCO) on early life stress using maternal separation (MS) rats was investigated. Anxiety-related behaviors were examined in MS rats using the elevated plus-maze (EPM) test. The changes of gene expressions by EOCO in the hippocampus of MS rats were analyzed using a microarray method. Rats in the MS groups were separated from their respective mothers from postnatal day (pnd) 14 to 28. Rats in the EOCO-treated groups were exposed to EOCO for 1 h or 2 h by inhalation from pnd 21 to 28. The EOCO-treated MS rats showed decreased anxiety-related behaviors compared to the MS rats in the EPM test. In the microarray analysis, EOCO downregulated the expressions of cytokine genes such as Ccl2, Il6, Cxcl10, Ccl19, and Il1rl in the hippocampus of MS rats, and it was also confirmed through RT-PCR. In particular, the expressions of Ccl2 and Il6 were predominantly decreased by EOCO in the hippocampus of MS rats. Interestingly, their protein expressions were also reduced by EOCO in MS rats. These results indicate that EOCO decreases MS-induced anxiety-related behaviors, and modulate cytokines, particularly Ccl2 and Il6, in the hippocampus of MS rats.

Keywords: anxiety-related behavior, Chamaecyparis obtuse, cytokine gene, early-life stress, maternal separation

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Authors: Hosein Maghsoudi

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Rheumatois arthritis (RA) is progressive inflammatory autoimmune diseases that primarily affect the joints, characterized by synovial hyperplasia and inflammatory cell infiltration, deformed and painful joints, which can lead tissue destruction, functional disability systemic complications, and early dead and socioeconomic costs. The cause of rheumatoid arthritis is unknown, but genetic and environmental factors are contributory and the prognosis is guarded. However, advances in understanding the pathogenesis of the disease have fostered the development of new therapeutics, with improved outcomes. The current treatment strategy, which reflects this progress, is to initiate aggressive therapy soon after diagnosis and to escalate the therapy, guided by an assessment of disease activity, in pursuit of clinical remission. The pathobiology of RA is multifaceted and involves T cells, B cells, fibroblast-like synoviocyte (FLSc) and the complex interaction of many pro-inflammatory cytokine. Novel biologic agents that target tumor necrosis or interlukin (IL)-1 and Il-6, in addition T- and B-cells inhibitors, have resulted in favorable clinical outcomes in patients with RA. Despite this, at least 30% of RA patients are résistance to available therapies, suggesting novel mediators should be identified that can target other disease-specific pathway or cell lineage. Among the inflammatory cell population that might participated in RA pathogenesis, FLSc are crucial in initiaing and driving RA in concert of cartilage and bone by secreting metalloproteinase (MMPs) into the synovial fluid and by direct invasion into extracellular matrix (ECM), further exacerbating joint damage. Invasion of fibroblast-like synoviocytes (FLSc) is critical in the pathogenesis of rheumatoid-arthritis. The metalloproteinase (MMPs) and activator of Toll-like receptor 4 (TLR4)/nuclear factor- κB pthway play a critical role in RA-FLS invasion induced by lipopolysaccharide (LPS). The present study aimed to explore the anti-invasion activity of Glycyrrhizic Acid as a pharmacologically safe phytochemical agent with potent anti-inflammatory properties on IL-1beta and TNF-alpha signalling pathways in Bovine fibroblast-like synoviocyte ex- vitro, on LPS-stimulated bovine FLS migration and invasion as well as MMP expression and explored the upstream signal transduction. Results showed that Glycyrrhizic Acid suppressed LPS-stimulated bovine FLS migration and invasion by inhibition MMP-9 expression and activity. In addition our results revealed that Glycyrrhizic Acid inhibited the transcriptional activity of MMP-9 by suppression the nbinding activity of NF- κB in the MMP-9 promoter pathway. The extract of licorice (Glycyrrhiza glabra L.) has been widely used for many centuries in the traditional Chinese medicine as native anti-allergic agent. Glycyrrhizin (GL), a triterpenoidsaponin, extracted from the roots of licorice is the most effective compound for inflammation and allergic diseases in human body. The biological and pharmacological studies revealed that GL possesses many pharmacological effects, such as anti-inflammatory, anti-viral and liver protective effects, and the biological effects, such as induction of cytokines (interferon-γ and IL-12), chemokines as well as extrathymic T and anti-type 2 T cells. GL is known in the traditional Chinese medicine for its anti-inflammatory effect, which is originally described by Finney in 1959. The mechanism of the GL-induced anti-inflammatory effect is based on different pathways of the GL-induced selective inhibition of the prostaglandin E2 production, the CK-II- mediated activation of both GL-binding lipoxygenas (gbLOX; 17) and PLA2, an anti-thrombin action of GL and production of the reactive oxygen species (ROS; GL exerts liver protection properties by inhibiting PLA2 or by the hydroxyl radical trapping action, leading to the lowering of serum alanine and aspartate transaminase levels. The present study was undertaken to examine the possible mechanism of anti-inflammatory properties GL on IL-1beta and TNF-alpha signalling pathways in bovine fibroblast-like synoviocyte ex-vivo, on LPS-stimulated bovine FLS migration and invasion as well as MMP expression and explored the upstream signal transduction. Our results clearly showed that treatment of bovine fibroblast-like synoviocyte with GL suppressed LPS-induced cell migration and invasion. Furthermore, it revealed that GL inhibited the transcription activity of MMP-9 by suppressing the binding activity of NF-κB in the MM-9 promoter. MMP-9 is an important ECM-degrading enzyme and overexpression of MMPs in important of RA-FLSs. LPS can stimulate bovine FLS to secret MMPs, and this induction is regulated at the transcription and translational levels. In this study, LPS treatment of bovine FLS caused an increase in MMP-2 and MMP-9 levels. The increase in MMP-9 expression and secretion was inhibited by ex- vitro. Furthermore, these effects were mimicked by MMP-9 siRNA. These result therefore indicate the the inhibition of LPS-induced bovine FLS invasion by GL occurs primarily by inhibiting MMP-9 expression and activity. Next we analyzed the functional significance of NF-κB transcription of MMP-9 activation in Bovine FLSs. Results from EMSA showed that GL suppressed LPS-induced NF-κB binding to the MMP-9 promotor, as NF-κB regulates transcriptional activation of multiple inflammatory cytokines, we predicted that GL might target NF-κB to suppress MMP-9 transcription by LPS. Myeloid differentiation-factor 88 (MyD88) and TIR-domain containing adaptor protein (TIRAP) are critical proteins in the LPS-induced NF-κB and apoptotic signaling pathways, GL inhibited the expression of TLR4 and MYD88. These results demonstrated that GL suppress LPS-induced MMP-9 expression through the inhibition of the induced TLR4/NFκB signaling pathway. Taken together, our results provide evidence that GL exerts anti-inflammatory effects by inhibition LPS-induced bovine FLSs migration and invasion, and the mechanisms may involve the suppression of TLR4/NFκB –mediated MMP-9 expression. Although further work is needed to clarify the complicated mechanism of GL-induced anti-invasion of bovine FLSs, GL might be used as a further anti-invasion drug with therapeutic efficacy in the treatment of immune-mediated inflammatory disease such as RA.

Keywords: glycyrrhizic acid, bovine fibroblast-like synoviocyte, tlr4/nf-κb, metalloproteinase-9

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Authors: Rachel Danielson, Brendan Bohannan, S.M. Tsai, Kyle Meyer, Jorge L.M. Rodrigues

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The Amazon Rainforest is a global diversity hotspot and crucial carbon sink, but approximately 20% of its total extent has been deforested- primarily for the establishment of cattle pasture. Understanding the impact of this large-scale disturbance on soil microbial community composition and activity is crucial in understanding potentially consequential shifts in nutrient or greenhouse gas cycling, as well as adding to the body of knowledge concerning how these complex communities respond to human disturbance. In this study, surface soils (0-10cm) were collected from three forests and three 45-year-old pastures in Rondonia, Brazil (the Amazon state with the greatest rate of forest destruction) in order to determine the impact of forest conversion on microbial communities involved in nitrogen fixation. Soil chemical and physical parameters were paired with measurements of microbial activity and genetic profiles to determine how community composition and process rates relate to environmental conditions. Measuring both the natural abundance of 15N in total soil N, as well as incorporation of enriched 15N2 under incubation has revealed that conversion of primary forest to cattle pasture results in a significant increase in the rate of nitrogen fixation by free-living diazotrophs. Quantification of nifH gene copy numbers (an essential subunit encoding the nitrogenase enzyme) correspondingly reveals a significant increase of genes in pasture compared to forest soils. Additionally, genetic sequencing of both nifH genes and transcripts shows a significant increase in the diversity of the present and metabolically active diazotrophs within the soil community. Levels of both organic and inorganic nitrogen tend to be lower in pastures compared to forests, with ammonium rather than nitrate as the dominant inorganic form. However, no significant or consistent differences in total, extractable, permanganate-oxidizable, or loss-on-ignition carbon are present between the two land-use types. Forest conversion is associated with a 0.5- 1.0 unit pH increase, but concentrations of many biologically relevant nutrients such as phosphorus do not increase consistently. Increases in free-living diazotrophic community abundance and activity appear to be related to shifts in carbon to nitrogen pool ratios. Furthermore, there may be an important impact of transient, low molecular weight plant-root-derived organic carbon on free-living diazotroph communities not captured in this study. Preliminary analysis of nitrogenase gene variant composition using NovoSeq metagenomic sequencing indicates that conversion of forest to pasture may significantly enrich vanadium-based nitrogenases. This indication is complemented by a significant decrease in available soil molybdenum. Very little is known about the ecology of diazotrophs utilizing vanadium-based nitrogenases, so further analysis may reveal important environmental conditions favoring their abundance and diversity in soil systems. Taken together, the results of this study indicate a significant change in nitrogen cycling and diazotroph community composition with the conversion of the Amazon Rainforest. This may have important implications for the sustainability of cattle pastures once established since nitrogen is a crucial nutrient for forage grass productivity.

Keywords: free-living diazotrophs, land use change, metagenomic sequencing, nitrogen fixation

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Authors: Yahia I. Mohamed, Ahmed I. Marzouk, Mohamed A. Yacout

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Aim of this work was to study the genetic basis for oil accumulation in olive fruit via tracking DGAT2 (Diacylglycerol acyltransferase type-2) gene in three Egyptian Origen Olive cultivars namely Toffahi, Hamed and Maraki using molecular marker techniques and bioinformatics tools. Results illustrate that, firstly: specific genomic band of Maraki cultivars was identified as DGAT2 (Diacylglycerol acyltransferase type-2) and identical for this gene in Olea europaea with 100 % of similarity. Secondly, differential genomic band of Maraki cultivars which produced from RAPD fingerprinting technique reflected predicted distinguished sequence which identified as DGAT2 (Diacylglycerol acyltransferase type-2) in Fragaria vesca subsp. Vesca with 76% of sequential similarity. Third and finally, specific genomic specific band of Hamed cultivars was indentified as two fragments, 1-Olea europaea cultivar Koroneiki diacylglycerol acyltransferase type 2 mRNA, complete cds with two matches regions with 99% or 2-PREDICTED: Fragaria vesca subsp. vesca diacylglycerol O-acyltransferase 2-like (LOC101313050), mRNA with 86% of similarity.

Keywords: Olea europaea, fingerprinting, diacylglycerol acyltransferase type-2 (DGAT2), Egypt

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Authors: Y. R. Adullayev, О. О. Karimzada

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Analytical expressions for inductances, current, ampere-turns, excitation winding, maximum width, coordinates of the levitation screen (LS) are derived for the calculation of electromagnetic devices based on tracking systems with levitation elements (TS with LS). Taking into account the expression of the complex magnetic resistance of the screen, the dependence of the screen width on the heating temperature of the physical and technical characteristics of the screen material and the relationship of the geometric dimensions of the magnetic circuit is established. Analytic expressions for a number of functional dependencies characterizing complex parameter relationships in explicit form are obtained and analyzed.

Keywords: tracking systems, levitation screens, electromagnetic levitation, excitation windings, magnetic cores, defining converter, receiving converter, electromagnetic force, electrical and magnetic resistance

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Authors: Gousilin Leandra Rocha Da Silva, Stéfani T. A. Dantas, Bruna F. Rossi, Erika R. Bonsaglia, Ivana G. Castilho, Terue Sadatsune, Ary Fernandes Júnior, Vera l. M. Rall

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Kidney failure causes decreased diuresis and accumulation of nitrogenous substances in the body. To increase patient survival, hemodialysis is used as a partial substitute for renal function. However, contamination of the water used in this treatment, causing bacteremia in patients, is a worldwide concern. The Burkholderia cepacia complex (Bcc), a group of bacteria with more than 20 species, is frequently isolated from hemodialysis water samples and comprises opportunistic bacteria, affecting immunosuppressed patients, due to its wide variety of virulence factors, in addition to innate resistance to several antimicrobial agents, contributing to the permanence in the hospital environment and to the pathogenesis in the host. The objective of the present work was to characterize molecularly and phenotypically Bcc isolates collected from the water and dialysate of the Hemodialysis Unit and from the blood of patients at a Public Hospital in Botucatu, São Paulo, Brazil, between 2019 and 2021. We used 33 Bcc isolates, previously obtained from blood cultures from patients with bacteremia undergoing hemodialysis treatment (2019-2021) and 24 isolates obtained from water and dialysate samples in a Hemodialysis Unit (same period). The recA gene was sequenced to identify the specific species among the Bcc group. All isolates were tested for the presence of some genes that encode virulence factors such as cblA, esmR, zmpA and zmpB. Considering the epidemiology of the outbreak, the Bcc isolates were molecularly characterized by Multi Locus Sequence Type (MLST) and by pulsed-field gel electrophoresis (PFGE). The verification and quantification of biofilm in a polystyrene microplate were performed by submitting the isolates to different incubation temperatures (20°C, average water temperature and 35°C, optimal temperature for group growth). The antibiogram was performed with disc diffusion tests on agar, using discs impregnated with cefepime (30µg), ceftazidime (30µg), ciprofloxacin (5µg), gentamicin (10µg), imipenem (10µg), amikacin 30µg), sulfametazol/trimethoprim (23.75/1.25µg) and ampicillin/sulbactam (10/10µg). The presence of ZmpB was identified in all isolates, while ZmpA was observed in 96.5% of the isolates, while none of them presented the cblA and esmR genes. The antibiogram of the 33 human isolates indicated that all were resistant to gentamicin, colistin, ampicillin/sulbactam and imipenem. 16 (48.5%) isolates were resistant to amikacin and lower rates of resistance were observed for meropenem, ceftazidime, cefepime, ciprofloxacin and piperacycline/tazobactam (6.1%). All isolates were sensitive to sulfametazol/trimethoprim, levofloxacin and tigecycline. As for the water isolates, resistance was observed only to gentamicin (34.8%) and imipenem (17.4%). According to PFGE results, all isolates obtained from humans and water belonged to the same pulsotype (1), which was identified by recA sequencing as B. cepacia¸, belonging to sequence type ST-767. By observing a single pulse type over three years, one can observe the persistence of this isolate in the pipeline, contaminating patients undergoing hemodialysis, despite the routine disinfection of water with peracetic acid. This persistence is probably due to the production of biofilm, which protects bacteria from disinfectants and, making this scenario more critical, several isolates proved to be multidrug-resistant (resistance to at least three groups of antimicrobials), turning the patient care even more difficult.

Keywords: hemodialysis, burkholderia cepacia, PFGE, MLST, multi drug resistance

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Authors: L. K. Akila

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Art activities can fund as a clinical support tool (CST) between interventions in Art Therapy to direct the client back towards better outcome goals. In the present study, during free art sessions, researcher examined the possibilities of motivating the adolescent group to involve in art making process by reflecting upon art intervention administered. Results show that adolescents’ reflecting upon their art works generated during the intervention; could change their perceptions and cognitions to improve their positive approach by restructuring their art expressions. Consequently, such reflections triggered and improved their emotions, feelings and ideas, and produced secure attachment between family, peers and teachers. By the end of interference, transformations experienced were effective more upon depression, self-image, and self-efficacy, and to a certain extent on aggressive patterns represented.

Keywords: adolescent, adolescent psychology, aggression, art, art therapy, cognition, depression, emotion, self-image

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Authors: Ireneusz Majsterek, Karolina Przybylowska, Lukasz Dziki, Adam Dziki, Jacek Kabzinski

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Colorectal cancer (CRC) is one of the deadliest cancers. Every year we see an increase in the number of cases, and in spite of intensive research etiology of the disease remains unknown. For many years, researchers are seeking to associate genetic factors with an increased risk of CRC, so far it has proved to be a compelling link between the MMR system of DNA repair and hereditary nonpolyposis colorectal cancers (HNPCC). Currently, research is focused on finding the relationship between the remaining DNA repair systems and an increased risk of developing colorectal cancer. The aim of the study was to determine the relationship between gene polymorphisms Ser835Ser of XPF gene and Gly23Ala of XPA gene–elements of NER DNA repair system, and modulation of the risk of colorectal cancer in the Polish population. Determination of the molecular basis of carcinogenesis process and predicting increased risk will allow qualifying patients to increased risk group and including them in preventive program. We used blood collected from 110 patients diagnosed with colorectal cancer. The control group consisted of equal number of healthy people. Genotyping was performed by TaqMan method. The obtained results indicate that the genotype 23Gly/Ala of XPA gene is associated with an increased risk of colorectal cancer, while 23Ala/Ala as well as TCT allele of Ser835Ser of XPF gene may reduce the risk of CRC.

Keywords: NER, colorectal cancer, XPA, XPF, polymorphisms

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Authors: Niousha Bagheri Khulenjani, Mohammad Saniee Abadeh

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Learning from very big datasets is a significant problem for most present data mining and machine learning algorithms. MicroRNA (miRNA) is one of the important big genomic and non-coding datasets presenting the genome sequences. In this paper, a hybrid method for the classification of the miRNA data is proposed. Due to the variety of cancers and high number of genes, analyzing the miRNA dataset has been a challenging problem for researchers. The number of features corresponding to the number of samples is high and the data suffer from being imbalanced. The feature selection method has been used to select features having more ability to distinguish classes and eliminating obscures features. Afterward, a Convolutional Neural Network (CNN) classifier for classification of cancer types is utilized, which employs a Genetic Algorithm to highlight optimized hyper-parameters of CNN. In order to make the process of classification by CNN faster, Graphics Processing Unit (GPU) is recommended for calculating the mathematic equation in a parallel way. The proposed method is tested on a real-world dataset with 8,129 patients, 29 different types of tumors, and 1,046 miRNA biomarkers, taken from The Cancer Genome Atlas (TCGA) database.

Keywords: cancer classification, feature selection, deep learning, genetic algorithm

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Authors: Xiaochen Mu

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Whether in common law countries that adhere to the "commercial copyright theory" or in civil law countries that center around "author's rights," the standards for judging originality have undergone continuous adjustments in response to the development of information technology. The adherence to originality standards does not arbitrarily dictate that all types of works be judged according to a single standard of originality, nor does it rigidly ignore the changes in creative methods and dissemination models brought about by technology. Adjustments and interpretations should be allowed based on the different forms of expression of works. Appropriate adjustments and interpretations are our response to technological advancements. However, what should be upheld are the principles and bottom lines of these adjustments and interpretations, namely the legislative intent and purpose of copyright law, which are to encourage the creation and dissemination of outstanding cultural works and to promote the flourishing of culture.

Keywords: generative artificial intelligence, originality, works, copyright

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Authors: H. Necef, A. Benayad

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Fungi are becoming more and more important in our life. Therefore, as a start for the symposium on filamentous fungi in biotechnology a short survey of the role of fungi in biotechnology. Salin soils occupy about 7% of land area; they are characterized by unsuitable physical conditions for the growth of living organisms. However, researches showed that some microorganisms especially fungi are able to grow and adapt to such extreme conditions; it is due to their ability to develop different physiological mechanisms in their adaptation. This is the first study on the physiological and biological characteristics of El-Beida marsh. Nine soil samples were taken at different points in two steps, the first was in winter (low temperature), and the second was in summer (high temperature). The physicochemical analyses of the soil were conducted, then the isolation process was applied using two methods, direct method and dilution method (10-1, 10-2, 10-3, 10-4). Different species of fungi were identified belong to 21 genera in addition to 3 yeast species, Aspergillus showed the highest proportion by 43%, then Penicillium by 20% then Alternaria by 7%, in addition to various genera in different proportions. As for the sampling periods, it was observed that the spread of fungi in winter was higher than in summer with the proportion 75.47% and 24.53% respectively. Some halotolerant fungi have a biotechnological importance especially if the salinity of the medium is necessary for the fermentation, and if the halotolerance genes of the fungus will define, this will open the research to study and improve this property for the industrial important micro-organisms.

Keywords: salinity, identification, aspergillus oryzae, halotolerance, fungi

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Authors: Zuzana Komrsková

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This paper shows the connection between emoticons and politeness in written computer-mediated communication. It studies if there are some differences in the use of emoticon between Czech and English written tweets. My assumptions about the use of emoticons were based on the use of greetings and thanks in real, face to face situations. The first assumption, that welcome greeting phrase would be accompanied by positive emoticon was correct. But for the farewell greeting both positive and negative emoticons are possible. My results show lower frequency of negative emoticons in this context. I also found quite often both positive and negative emoticon in the same tweet. The expression of gratitude is associated with positive emotions. The results show that emoticons accompany polite phrases of greeting and thanks very often both in Czech and English. The use of emoticons with studied polite phrases shows that emoticons have become an integral part of these phrases.

Keywords: Czech, emoticon, english, politeness, twitter

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Authors: L. K. Davis

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The effects of the evolution force are observable in nature at all structural levels ranging from small molecular systems to conversely enormous biospheric systems. However, the evolution force and work associated with formation of biological structures has yet to be described mathematically or theoretically. In addressing the conundrum, we consider evolution from a unique perspective and in doing so we introduce the “Fundamental Theory of the Evolution Force: FTEF”. We utilized synthetic evolution artificial intelligence (SYN-AI) to identify genomic building blocks and to engineer 14-3-3 ζ docking proteins by transforming gene sequences into time-based DNA codes derived from protein hierarchical structural levels. The aforementioned served as templates for random DNA hybridizations and genetic assembly. The application of hierarchical DNA codes allowed us to fast forward evolution, while dampening the effect of point mutations. Natural selection was performed at each hierarchical structural level and mutations screened using Blosum 80 mutation frequency-based algorithms. Notably, SYN-AI engineered a set of three architecturally conserved docking proteins that retained motion and vibrational dynamics of native Bos taurus 14-3-3 ζ.

Keywords: 14-3-3 docking genes, synthetic protein design, time-based DNA codes, writing DNA code from scratch

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Authors: Maryam Saeidi, Ehsan Motamedian, Seyed Abbas Shojaosadati

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Zymomonas mobilis is known as an example of the uncoupled growth phenomenon. This microorganism also has a unique metabolism that degrades glucose by the Entner–Doudoroff (ED) pathway. In this paper, a genome-scale metabolic model including 434 genes, 757 reactions and 691 metabolites was reconstructed to simulate uncoupled growth and study its effect on flux distribution in the central metabolism. The model properly predicted that ATPase was activated in experimental growth yields of Z. mobilis. Flux distribution obtained from model indicates that the major carbon flux passed through ED pathway that resulted in the production of ethanol. Small amounts of carbon source were entered into pentose phosphate pathway and TCA cycle to produce biomass precursors. Predicted flux distribution was in good agreement with experimental data. The model results also indicated that Z. mobilis metabolism is able to produce biomass with maximum growth yield of 123.7 g (mol glucose)-1 if ATP synthase is coupled with growth and produces 82 mmol ATP gDCW-1h-1. Coupling the growth and energy reduced ethanol secretion and changed the flux distribution to produce biomass precursors.

Keywords: genome-scale metabolic model, Zymomonas mobilis, uncoupled growth, flux distribution, ATP dissipation

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Authors: Man-Ho Oh

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Membrane localized Leucine-Rich-Repeat Receptor-Like Kinases (LRR-RLKs) play crucial roles in plant growth and abiotic/biotic stress responses in higher plants including Arabidopsis and Brassica species. Among several Receptor-Like Kinases (RLKs), Leucine-Rich-Repeat Receptor-Like-Kinases (LRR-RLKs) are the major group of genes that play crucial roles related to growth, development and stress conditions in plant system. Since it is involved in several functional roles, it seems to be very important to investigate their roles in higher plants. We are particularly interested in brassinosteroid (BR) signaling, which is mediated by the BRASSINOSTEROID INSENSITIVE 1 (BRI1) receptor kinase and its co-receptor, BRI1-ASSOCIATED KINASE 1 (BAK1). Autophosphorylation of receptor kinases is recognized to be an important process in activation of signaling in higher plants. Although the plant receptors are generally classified as Ser/Thr protein kinases, many other receptor kinases including BRI1 and BAK1 are shown to autophosphorylate on Tyr residues in addition to Ser/Thr. As an interesting result, we determined that several 14-3-3 regulatory proteins bind to BRI1-CD and are phosphorylated by several receptor kinases in vitro, suggesting that BRI1 is critical for diverse signaling.

Keywords: autophosphorylation, brassinosteroid, BRASSINOSTEROID INSENSITIVE 1, BRI1-ASSOCIATED KINASE 1, Leucine-Rich-Repeat Receptor-Like Kinases (LRR-RLKs)

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Authors: Alexandra-Monica Toma

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As the internet became a ruling force of society, computer-mediated communication has enriched its methods to convey meaning by combining linguistic means to visual means of expressivity. One of the elements of cyberspace is what we call a meme, a succinct, visually engaging tool used to communicate ideas or emotions, usually in a funny or ironic manner. Coined by Richard Dawkings in the late 1970s to refer to cultural genes, this term now denominates a special type of vernacular language used to share content on the internet. This research aims to analyse the basic mechanism that stands at the basis of meme creation as a blend of innovation and imitation and will approach some of the most widely used image macros remixed to generate new content while also pointing out success strategies. Moreover, this paper discusses whether memes can transcend the light-hearted and playful mood they mirror and become biting and sharp cultural comments. The study also uses the concept of multimodality and stresses how the text interacts with image, discussing three types of relations between the two: symmetry, amplification, and contradiction. We will furthermore show that memes are cultural artifacts and virtual tropes highly dependent on context and societal issues by using a corpus of memes created related to the COVID-19 pandemic.

Keywords: context, computer-mediated communication, memes, multimodality

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Authors: S. Aizikovich, L. Krenev, Y. Tokovyy, Y. C. Wang

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An approximate analytical-numerical solution to the axisymmetric problem on thermo-mechanical indentation of a flat cylindrical punch into an arbitrarily non-homogeneous elastic half-space is constructed by making use of the bilateral asymptotic method. The key point of this method lies in evaluation of the ker¬nels in the obtained integral equations by making use of a numerical technique. Once the structure of the kernel is defined, it then is approximated by an analytical expression of special kind so that the solution of the integral equation can be achieved analytically. This fact allows for construction of the solution in an analytical form, which is convenient for analysis of the mechanical effects concerned with arbitrarily presumed non-homogeneity of the material.

Keywords: contact problem, circular punch, arbitrarily-nonhomogeneous halfspace

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Authors: M. Lizzy Madiwani, Ignatious Ncube, Evelyn Madoroba

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This study was designed to determine the distribution of pathogenic bacteria in household raised chickens and study their virulence and antibiotic profiles. For this purpose, 40 chickens were purchased from families in the Capricorn district and sacrificed for sampling. Tissues were cultured on different bacteriological media followed by biotyping using Matrix-assisted Laser Desorption Ionization-time of Flight (MALDI-TOF). Disk diffusion test was performed to determine the antibiotic susceptibility profiles of these bacteria. Out of a total of 160 tissue samples evaluated, E. coli and Salmonella were detected in these tissues. Furthermore, determination of the pathogenic E. coli and Salmonella strains at species level using primer sets that target selected genes of interest in the polymerase chain reaction (PCR) assay was employed. The invA gene, a confirmatory gene of Salmonella was detected in all the Salmonella isolates. The study revealed that there is a high distribution of Salmonella and pathogenic E. coli in these chickens. Therefore, further studies on identification at the species level are highly recommended to provide management and sanitation practices to lower this prevalence. The antimicrobial susceptibly data generated from this study can be a valuable reference to veterinarians for treating bacterial diseases in poultry.

Keywords: antimicrobial, Escherichia coli, pathogens, Salmonella

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Authors: Reem Al-Shidhani, Isabelle S. R. Storer, Michael J. Bromley, Lydia Tabernero

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Invasive fungal diseases are an increasing global health concern that contributes to the high mortality rates in immunocompromised patients. The rising of antifungal resistance severely lowers the efficacy of the limited antifungal agents available. New antifungal drugs that target new mechanisms are necessary to tackle the current shortfalls. Amongst post- modifications, phosphorylation is a predominant and an outstanding protein alteration in all eukaryotes. In fungi, protein phosphorylation plays a vital role in many signal transduction pathways, including cell cycle, cell growth, metabolism, transcription, differentiation, proliferation, and virulence. The investigation of Aspergillus fumigatus phosphatases revealed seven genes essential for viability. Inhibiting one of these phosphatases is a new interesting route to develop novel antifungal drugs. In this study, we carried out an early drug discovery process targeting oneessential phosphatase, GlcA. Here, we report the identification of new GlcA inhibitors that show antifungal activity. These important finding open a new avenue to the development of novel antifungals to expand the current narrow arsenal of clinical candidates.

Keywords: invasive fungal diseases, phosphatases, GlcA, competitive inhibitors

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Authors: Claire Harrison, Raajit K. Rampal, Vikas Gupta, Srdan Verstovsek, Moshe Talpaz, Jean-Jacques Kiladjian, Ruben Mesa, Andrew Kuykendall, Alessandro Vannucchi, Francesca Palandri, Sebastian Grosicki, Timothy Devos, Eric Jourdan, Marielle J. Wondergem, Haifa Kathrin Al-Ali, Veronika Buxhofer-Ausch, Alberto Alvarez-Larrán, Sanjay Akhani, Rafael Muñoz-Carerras, Yury Sheykin, Gozde Colak, Morgan Harris, John Mascarenhas

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Myelofibrosis (MF) is characterized by bone marrow fibrosis, anemia, splenomegaly and constitutional symptoms. Progressive bone marrow fibrosis results from aberrant megakaryopoeisis and expression of proinflammatory cytokines, both of which are heavily influenced by bromodomain and extraterminal domain (BET)-mediated gene regulation and lead to myeloproliferation and cytopenias. Pelabresib (CPI-0610) is an oral small-molecule investigational inhibitor of BET protein bromodomains currently being developed for the treatment of patients with MF. It is designed to downregulate BET target genes and modify nuclear factor kappa B (NF-κB) signaling. MANIFEST-2 was initiated based on data from Arm 3 of the ongoing Phase 2 MANIFEST study (NCT02158858), which is evaluating the combination of pelabresib and ruxolitinib in Janus kinase inhibitor (JAKi) treatment-naïve patients with MF. Primary endpoint analyses showed splenic and symptom responses in 68% and 56% of 84 enrolled patients, respectively. MANIFEST-2 (NCT04603495) is a global, Phase 3, randomized, double-blind, active-control study of pelabresib and ruxolitinib versus placebo and ruxolitinib in JAKi treatment-naïve patients with primary MF, post-polycythemia vera MF or post-essential thrombocythemia MF. The aim of this study is to evaluate the efficacy and safety of pelabresib in combination with ruxolitinib. Here we report updates from a recent protocol amendment. The MANIFEST-2 study schema is shown in Figure 1. Key eligibility criteria include a Dynamic International Prognostic Scoring System (DIPSS) score of Intermediate-1 or higher, platelet count ≥100 × 10^9/L, spleen volume ≥450 cc by computerized tomography or magnetic resonance imaging, ≥2 symptoms with an average score ≥3 or a Total Symptom Score (TSS) of ≥10 using the Myelofibrosis Symptom Assessment Form v4.0, peripheral blast count <5% and Eastern Cooperative Oncology Group performance status ≤2. Patient randomization will be stratified by DIPSS risk category (Intermediate-1 vs Intermediate-2 vs High), platelet count (>200 × 10^9/L vs 100–200 × 10^9/L) and spleen volume (≥1800 cm^3 vs <1800 cm^3). Double-blind treatment (pelabresib or matching placebo) will be administered once daily for 14 consecutive days, followed by a 7 day break, which is considered one cycle of treatment. Ruxolitinib will be administered twice daily for all 21 days of the cycle. The primary endpoint is SVR35 response (≥35% reduction in spleen volume from baseline) at Week 24, and the key secondary endpoint is TSS50 response (≥50% reduction in TSS from baseline) at Week 24. Other secondary endpoints include safety, pharmacokinetics, changes in bone marrow fibrosis, duration of SVR35 response, duration of TSS50 response, progression-free survival, overall survival, conversion from transfusion dependence to independence and rate of red blood cell transfusion for the first 24 weeks. Study recruitment is ongoing; 400 patients (200 per arm) from North America, Europe, Asia and Australia will be enrolled. The study opened for enrollment in November 2020. MANIFEST-2 was initiated based on data from the ongoing Phase 2 MANIFEST study with the aim of assessing the efficacy and safety of pelabresib and ruxolitinib in JAKi treatment-naïve patients with MF. MANIFEST-2 is currently open for enrollment.

Keywords: CPI-0610, JAKi treatment-naïve, MANIFEST-2, myelofibrosis, pelabresib

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Authors: Muhammad Sohail Khan, Rehan Ali Shah

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The present paper applies the optimal homotopy perturbation method (OHPM) and the optimal homotopy asymptotic method (OHAM) introduced recently to obtain analytic approximations of the non-linear equations modeling the flow of polymer in case of wire coating of a corotational Maxwell fluid. Expression for the velocity field is obtained in non-dimensional form. Comparison of the results obtained by the two methods at different values of non-dimensional parameter l₁₀, reveal that the OHPM is more effective and easy to use. The OHPM solution can be improved even working in the same order of approximation depends on the choices of the auxiliary functions.

Keywords: corotational Maxwell model, optimal homotopy asymptotic method, optimal homotopy perturbation method, wire coating die

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Authors: Yahia Massinissa, Melakhessou Med Akram, Mezahdia Mehdi, Marref Salah Eddine

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Cytokines are natural proteins which act as true intercellular communication signals in immune and inflammatory responses. Reverse signaling pathways that activate cytokines help to regulate different functions at the target cell, causing its activation, its proliferation, the differentiation, its survival or death. It was shown that malfunctioning of the cytokine regulation, particularly over-expression, contributes to the onset and development of certain serious diseases such as chronic rheumatoid arthritis, Crohn's disease, psoriasis, lupus. The action mode of Kinoid® technology is based on the principle vaccine: The patient's immune system is activated so that it neutralizes itself and the factor responsible for the disease. When applied specifically to autoimmune diseases, therapeutic vaccination allows the body to neutralize cytokines (proteins) overproduced through a highly targeted stimulation of the immune system.

Keywords: cytokines, Kinoid tech, auto-immune diseases, vaccination

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Authors: Abdelaziz Messis, Azzeddine Bettache, Nawel Boucherba, Said Benallaoua, Mouloud Kecha

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Actinobacteria are of special biotechnological interest since they are known to produce chemically diverse compounds with a wide range of biological activity. This distinct clade of Gram-positve bacteria include some of the key antibiotic producers and are also sources of several bioactive compounds, established commercially a newly filamentous bacteria was recovered from Tikjda forest soil (Algeria) for its high antifungal activity against various pathogenic and phytopathogenic fungi. The nucleotide sequence of the 16S rRNA gene (1454 pb) of Streptomyces sp. TKJ2 exhibited close similarity (99 %) with other Streptomyces16S rRNA genes. Antifungal metabolite production of Streptomyces sp TKJ2 was evaluated using six different fermentation media. The extracellular products contained potent antifungal agents. Antifungal protein produced by Streptomyces sp. TKJ2 on PCA medium has been purified by ammonium sulfate precipitation, SPE column chromatography and high-performance liquid chromatography in a reverse-phase column. The UV chromatograms of the active fractions obtained at 214 nm by NanoLC-ESI-MS/MS have different molecular weights. The F20 Peptidic fraction obtained from culture filtrat of Streptomyces sp. TKJ2 precipitated at 30% of ammonium sulfate was selected for analysis by infusion ESI-MS which yielded a singly charged ion mass of 437.17 Da.

Keywords: actinobacteria, antifungal protein, chromatography, Streptomyces

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