Search results for: stem cell fate decision

Authors: Paula I. Buonfiglio, Carlos David Bruque, Lucia Salatino, Vanesa Lotersztein, Sebastián Menazzi, Paola Plazas, Ana Belén Elgoyhen, Viviana Dalamón

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Hearing loss (HL) is the most prevalent sensorineural disorder affecting about 10% of the global population, with more than half due to genetic causes. About 1 in 500-1000 newborns present congenital HL. Most of the patients are non-syndromic with an autosomal recessive mode of inheritance. To date, more than 100 genes are related to HL. Therefore, the Whole-exome sequencing (WES) technique has become a cost-effective alternative approach for molecular diagnosis. Nevertheless, new challenges arise from the detection of novel variants, in particular missense changes, which can lead to a spectrum of genotype-to-phenotype correlations, which is not always straightforward. In this work, we aimed to identify the genetic causes of HL in isolated and familial cases by designing a multistep approach to analyze target genes related to hearing impairment. Moreover, we performed in silico and in vivo analyses in order to further study the effect of some of the novel variants identified in the hair cell function using the zebrafish model. A total of 650 patients were studied by Sanger Sequencing and Gap-PCR in GJB2 and GJB6 genes, respectively, diagnosing 15.5% of sporadic cases and 36% of familial ones. Overall, 50 different sequence variants were detected. Fifty of the undiagnosed patients with moderate HL were tested for deletions in STRC gene by Multiplex ligation-dependent probe amplification technique (MLPA), leading to 6% of diagnosis. After this initial screening, 50 families were selected to be analyzed by WES, achieving diagnosis in 44% of them. Half of the identified variants were novel. A missense variant in MYO6 gene detected in a family with postlingual HL was selected to be further analyzed. A protein modeling with AlphaFold2 software was performed, proving its pathogenic effect. In order to functionally validate this novel variant, a knockdown phenotype rescue assay in zebrafish was carried out. Injection of wild-type MYO6 mRNA in embryos rescued the phenotype, whereas using the mutant MYO6 mRNA (carrying c.2782C>A variant) had no effect. These results strongly suggest the deleterious effect of this variant on the mobility of stereocilia in zebrafish neuromasts, and hence on the auditory system. In the present work, we demonstrated that our algorithm is suitable for the sequential multigenic approach to HL in our cohort. These results highlight the importance of a combined strategy in order to identify candidate variants as well as the in silico and in vivo studies to analyze and prove their pathogenicity and accomplish a better understanding of the mechanisms underlying the physiopathology of the hearing impairment.

Keywords: diagnosis, genetics, hearing loss, in silico analysis, in vivo analysis, WES, zebrafish

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Authors: C. Watson, T. Glare, M. O'Callaghan, M. Hurst

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The endemic New Zealand grass grub (Costelytra giveni, Coleoptera: Scarabaeidae) is an economically significant grassland pest in New Zealand. Due to their impacts on production within the agricultural sector, one of New Zealand's primary industries, several methods are being used to either control or prevent the establishment of new grass grub populations in the pasture. One such method involves the use of a biopesticide based on the bacterium Serratia entomophila. This species is one of the causative agents of amber disease, a chronic disease of the larvae which results in death via septicaemia after approximately 2 to 3 months. The ability of S. entomophila to cause amber disease is dependant upon the presence of the amber disease associated plasmid (pADAP), which encodes for the key virulence determinants required for the establishment and maintenance of the disease. Following the collapse of grass grub populations within the soil, resulting from either natural population build-up or application of the bacteria, non-pathogenic plasmid-free Serratia strains begin to predominate within the soil. Whilst the interactions between S. entomophila and grass grub larvae are well studied, less information is known on the interactions between plasmid-bearing and plasmid-free strains, particularly the potential impact of these interactions upon the efficacy of an applied biopesticide. Using a range of constructed strains with antibiotic tags, in vitro (broth culture) and in vivo (soil and larvae) experiments were conducted using inoculants comprised of differing ratios of isogenic pathogenic and non-pathogenic Serratia strains, enabling the relative growth of pADAP+ and pADAP- strains under competition conditions to be assessed. In nutrient-rich, the non-pathogenic pADAP- strain outgrew the pathogenic pADAP+ strain by day 3 when inoculated in equal quantities, and by day 5 when applied as the minority inoculant, however, there was an overall gradual decline in the number of viable bacteria for both strains over a 7-day period. Similar results were obtained in additional experiments using the same strains and continuous broth cultures re-inoculated at 24-hour intervals, although in these cultures, the viable cell count did not diminish over the 7-day period. When the same ratios were assessed in soil microcosms with limited available nutrients, the strains remained relatively stable over a 2-month period. Additionally, in vivo grass grub co-infections assays using the same ratios of tagged Serratia strains revealed similar results to those observed in the soil, but there was also evidence of horizontal transfer of pADAP from the pathogenic to the non-pathogenic strain within the larval gut after a period of 4 days. Whilst the influence of competition is more apparent in broth cultures than within the soil or larvae, further testing is required to determine whether this competition between pathogenic and non-pathogenic Serratia strains has any influence on efficacy and disease progression, and how this may impact on the ability of S. entomophila to cause amber disease within grass grub larvae when applied as a biopesticide.

Keywords: biological control, entomopathogen, microbial ecology, New Zealand

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Authors: Priyanka Dutta Chowdhury

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A globalized connected world, calling loud for a composite culture, was still not able to erase the pain of a desired nationalism based on cultural identity. In the South Asian region, the random drawing of the boundaries without taking the ethnic aspect into consideration have always challenged the very basis of the existence of certain groups. The urge to reunify with the fellow brothers on both sides of the border have always called for a chaos and schism in the countries of this region. Sometimes this became a tool to bargain with the state and find a favorable position in the power structure on the basis of cultural identity. In Pakistan and Afghanistan, the Pakhtuns who are divided across the border of the two countries, from the inception of creation of Pakistan have posed various challenges and hampered the growth of a consolidated nation. The Pakhtuns or Pashtuns of both Pakistan and Afghanistan have a strong cultural affinity which blurs their physical distancing and calls for a nationalism based on this ethnic affiliation. Both the sides wanted to create Pakhtunistan unifying all the Pakhtuns of the region. For long, this group have denied to accept the Durand line separating the two. This was an area of concern especially for the Pakhtuns of Pakistan torn between the decision either to join Afghanistan, create a nation of their own or be a part of Pakistan. This ethnic issue became a bone of contention between the two countries. Later, though well absorbed and recognized in the respective countries, they have fought for their identity and claimed for a dominant position in the politics of the nations. Because of the porous borders often influx of refugees was seen especially during Afghan Wars and later many extremists’ groups were born from them especially the Taliban. In the recent string of events, when the Taliban, who are mostly Pakhtuns ethnically, came in power in Afghanistan, a wave of sympathy arose in Pakistan. This gave a strengthening position to the religious Pakhtuns across the border. It is to be noted here that a fragmented Pakhtun identity between the religious and seculars were clearly visible, voicing for their place in the political hierarchy of the country with a vision distinct from each other especially in Pakistan. In this context the paper tries to evaluate the reasons for this cultural turmoil between the countries and this ethnic group. It also aims to analyze the concept of how the identity politics still holds its relevance in the contemporary world. Additionally, the recent trend of fragmented identity points towards instrumentalization of this ethnic groups, who are engaged in the bargaining process with the state for a robust position in the power structure. In the end, the paper aims to deduct from the theoretical conditions of identity politics, whether this is a primordial or a situational tool to have a visibility in the power structure of the contemporary world.

Keywords: cultural identity, identity politics, instrumentalization of identity pakhtuns, power structure

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Authors: Brajendra S. Sengar, Vivek Garg, Gaurav Siddharth, Nisheka Anadkat, Amitesh Kumar, Shaibal Mukherjee

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The optimal band gap (~ 1 to 1.5 eV) and high absorption coefficient ~104 cm⁻¹ has made Cu₂ZnSn(S,Se)₄ (CZTSSe) films as one of the most promising absorber materials in thin-film photovoltaics. Additionally, CZTSSe consists of elements that are abundant and non-toxic, makes it even more favourable. The CZTSSe thin films are grown at 100 to 500ᵒC substrate temperature (Tsub) on Soda lime glass (SLG) substrate by Elettrorava dual ion beam sputtering (DIBS) system by utilizing a target at 2.43x10⁻⁴ mbar working pressure with RF power of 45 W in argon ambient. The chemical composition, depth profiling, structural properties and optical properties of these CZTSSe thin films prepared on SLG were examined by energy dispersive X-ray spectroscopy (EDX, Oxford Instruments), Hiden secondary ion mass spectroscopy (SIMS) workstation with oxygen ion gun of energy up to 5 keV, X-ray diffraction (XRD) (Rigaku Cu Kα radiation, λ=.154nm) and Spectroscopic Ellipsometry (SE, M-2000D from J. A. Woollam Co., Inc). It is observed that from that, the thin films deposited at Tsub=200 and 300°C show Cu-poor and Zn-rich states (i.e., Cu/(Zn + Sn) < 1 and Zn/Sn > 1), which is not the case for films grown at other Tsub. It has been reported that the CZTSSe thin films with the highest efficiency are typically at Cu-poor and Zn-rich states. The values of band gap in the fundamental absorption region of CZTSSe are found to be in the range of 1.23-1.70 eV depending upon the Cu/(Zn+Sn) ratio. It is also observed that there is a decline in optical band gap with the increase in Cu/(Zn+Sn) ratio (evaluated from EDX measurement). Cu-poor films are found to have higher optical band gap than Cu-rich films. The decrease in the band gap with the increase in Cu content in case of CZTSSe films may be attributed to changes in the extent of p-d hybridization between Cu d-levels and (S, Se) p-levels. CZTSSe thin films with Cu/(Zn+Sn) ratio in the range 0.86–1.5 have been successfully deposited using DIBS. Optical band gap of the films is found to vary from 1.23 to 1.70 eV based on Cu/(Zn+Sn) ratio. CZTSe films with Cu/ (Zn+Sn) ratio of .86 are found to have optical band gap close to the ideal band gap (1.49 eV) for highest theoretical conversion efficiency. Thus by tailoring the value of Cu/(Zn+Sn), CZTSSe thin films with the desired band gap could be obtained. Acknowledgment: We are thankful to DIBS, EDX, and XRD facility equipped at Sophisticated Instrument Centre (SIC) at IIT Indore. The authors B. S. S and A. K. acknowledge CSIR, and V. G. acknowledges UGC, India for their fellowships. B. S. S is thankful to DST and IUSSTF for BASE Internship Award. Prof. Shaibal Mukherjee is thankful to DST and IUSSTF for BASE Fellowship and MEITY YFRF award. This work is partially supported by DAE BRNS, DST CERI, and DST-RFBR Project under India-Russia Programme of Cooperation in Science and Technology. We are thankful to Mukul Gupta for SIMS facility equipped at UGC-DAE Indore.

Keywords: CZTSSe, DIBS, EDX, solar cell

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Authors: Abdul-Ganiyu Fuseini, Bernice Redley, Helen Rawson, Lenore Lay, Debra Kerr

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Aim: The study aimed to develop and validate a culturally appropriate patient-reported outcome measure for measuring dignity for older adults during acute hospital admissions. Design: A three-phased mixed-method sequential exploratory design was used. Methods: Concept elicitation and generation of items for the scale was informed by older adults’ perspectives about dignity during acute hospitalization and a literature review. Content validity evaluation and pre-testing were undertaken using standard instrument development techniques. A cross-sectional survey design was conducted involving 270 hospitalized older adults for evaluation of construct and convergent validity, internal consistency reliability, and test–retest reliability of the scale. Analysis was performed using Statistical Package for the Social Sciences, version 25. Reporting of the study was guided by the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) checklist. Results: We established the 15-item Hospitalized Older Adults’ Dignity Scale that has a 5-factor structure: Shared Decision-Making (3 items); Healthcare Professional-Patient Communication (3 items); Patient Autonomy (4 items); Patient Privacy (2 items); and Respectful Care (3 items). Excellent content validity, adequate construct and convergent validity, acceptable internal consistency reliability, and good test-retest reliability were demonstrated. Conclusion: We established the Hospitalized Older Adults Dignity Scale as a valid and reliable scale to measure dignity for older adults during acute hospital admissions. Future studies using confirmatory factor analysis are needed to corroborate the dimensionality of the factor structure and external validity of the scale. Routine use of the scale may provide information that informs the development of strategies to improve dignity-related care in the future. Impact: The development and validation of the Hospitalized Older Adults Dignity Scale will provide healthcare professionals with a feasible and reliable scale for measuring older adults’ dignity during acute hospitalization. Routine use of the scale may enable the capturing and incorporation of older patients’ perspectives about their healthcare experience and provide information that informs the development of strategies to improve dignity-related care in the future.

Keywords: dignity, older adults, hospitalisation, scale, patients, dignified care, acute care

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Authors: Malkhaz Jokhadze, Vakhtang Mshvildadze, Levan Makaradze, Ekaterine Mosidze, Salome Barbaqadze, Mariam Murtazashvili, Dali Berashvili, Koba sivsivadze, Lasha Bakuridze, Aliosha Bakuridze

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Essential oils are one of the most important groups of biologically active substances present in plants. Due to the chemical diversity of components, essential oils and their preparations have a wide spectrum of pharmacological action. They have bactericidal, antiviral, fungicidal, antiprotozoal, anti-inflammatory, spasmolytic, sedative and other activities. They are expectorant, spasmolytic, sedative, hypotensive, secretion enhancing, antioxidant remedies. Based on preliminary pharmacological studies, we have developed a formulation called “Phytobiotic” containing essential oils, a feed additive for poultry as an alternative to antibiotics. Phytobiotic is a water-soluble powder containing a composition of essential oils of thyme, clary, monarda and auxiliary substances: dry extract of liquorice and inhalation lactose. On this stage of research, the goal was to study the chemical composition of provided phytobiotic, identify the main substances and determine their quantity, investigate the biological activity of phytobiotic through in vitro and in vivo studies. Using gas chromatography-mass spectrometry, 38 components were identified in phytobiotic, representing acyclic-, monocyclic-, bicyclic-, and sesquiterpenes. Together with identification of main active substances, their quantitative content was determined, including acyclic terpene alcohol β-linalool, acyclic terpene ketone linalyl acetate, monocyclic terpenes: D-limonene and γ-terpinene, monocyclic aromatic terpene thymol. Provided phytobiotic has pronounced and at the same time broad spectrum of antibacterial activity. In the cell model, phytobiotic showed weak antioxidant activity, and it was stronger in the ORAC (chemical model) tests. Meanwhile anti-inflammatory activity was also observed. When fowls were supplied feed enriched with phytobiotic, it was observed that gained weight of the chickens in the experimental group exceeded the same data for the control group during the entire period of the experiment. The survival rate of broilers in the experimental group during the growth period was 98% compared to -94% in the control group. As a result of conducted researches probable four different mechanisms which are important for the action of phytobiotics were identified: sensory, metabolic, antioxidant and antibacterial action. General toxic, possible local irritant and allergenic effects of phytobiotic were also investigated. Performed assays proved that formulation is safe.

Keywords: clary, essential oils, monarda, poultry, phytobiotics, thyme

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Authors: Celine Bonnaud, Isabelle Billard, Nicolas Papaiconomou, Eric Chainet

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Thanks to their high magnetization and low mass, permanent magnets (NdFeB and SmCo) have quickly became essential for new energies (wind turbines, electrical vehicles…). They contain large quantities of neodymium, samarium and dysprosium, that have been recently classified as critical elements and that therefore need to be recycled. Electrochemical processes including electrodissolution followed by electrodeposition are an elegant and environmentally friendly solution for the recycling of such lanthanides contained in permanent magnets. However, electrochemistry of the lanthanides is a real challenge as their standard potentials are highly negative (around -2.5V vs ENH). Consequently, non-aqueous solvents are required. Ionic liquids (IL) are novel electrolytes exhibiting physico-chemical properties that fulfill many requirements of the sustainable chemistry principles, such as extremely low volatility and non-flammability. Furthermore, their chemical and electrochemical properties (solvation of metallic ions, large electrochemical windows, etc.) render them very attractive media to implement alternative and sustainable processes in view of integrated processes. All experiments that will be presented were carried out using butyl-methylpyrrolidinium bis(trifluoromethanesulfonyl)imide. Linear sweep, cyclic voltammetry and potentiostatic electrochemical techniques were used. The reliability of electrochemical experiments, performed without glove box, for the classic three electrodes cell used in this study has been assessed. Deposits were obtained by chronoamperometry and were characterized by scanning electron microscopy and energy-dispersive X-ray spectroscopy. The IL cathodic behavior under different constraints (argon, nitrogen, oxygen atmosphere or water content) and using several electrode materials (Pt, Au, GC) shows that with argon gas flow and gold as a working electrode, the cathodic potential can reach the maximum value of -3V vs Fc+/Fc; thus allowing a possible reduction of lanthanides. On a gold working electrode, the reduction potential of samarium and neodymium was found to be -1.8V vs Fc+/Fc while that of dysprosium was -2.1V vs Fc+/Fc. The individual deposits obtained were found to be porous and presented some significant amounts of C, N, F, S and O atoms. Selective deposition of neodymium in presence of dysprosium was also studied and will be discussed. Next, metallic Sm, Nd and Dy electrodes were used in replacement of Au, which induced changes in the reduction potential values and the deposit structures of lanthanides. The individual corrosion potentials were also measured in order to determine the parameters influencing the electrodissolution of these metals. Finally, a full recycling process was investigated. Electrodissolution of a real permanent magnet sample was monitored kinetically. Then, the sequential electrodeposition of all lanthanides contained in the IL was investigated. Yields, quality of the deposits and consumption of chemicals will be discussed in depth, in view of the industrial feasibility of this process for real permanent magnets recycling.

Keywords: electrodeposition, electrodissolution, ionic liquids, lanthanides, rcycling

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Authors: Mustafa M. Donma, Orkide Donma

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Iron is physiologically essential. However, it also participates in the catalysis of free radical formation reactions. Its deficiency is associated with amplified health risks. This trace element establishes some links with another physiological process related to cell death, apoptosis. Both iron deficiency and iron overload are closely associated with apoptosis. Soluble tumor necrosis factor-like weak inducer of apoptosis (sTWEAK) has the ability to trigger apoptosis and plays a dual role in the physiological versus pathological inflammatory responses of tissues. The aim of this study was to investigate the status of these parameters as well as the associations among them in children with obesity, a low-grade inflammatory state. The study was performed on groups of children with normal body mass index (N-BMI) and obesity. Forty-three children were included in each group. Based upon age- and sex-adjusted BMI percentile tables prepared by World Health Organization, children whose values varied between 85 and 15 were included in N-BMI group. Children whose BMI percentile values were between 99 and 95 comprised obese (OB) group. Institutional ethical committee approval and informed consent forms were taken prior to the study. Anthropometric measurements (weight, height, waist circumference, hip circumference, head circumference, neck circumference) and blood pressure values (systolic blood pressure and diastolic blood pressure) were recorded. Routine biochemical analysis including serum iron, total iron binding capacity (TIBC), transferrin saturation percent (Tf Sat %), and ferritin were performed. Soluble tumor necrosis factor-like weak inducer of apoptosis levels were determined by enzyme-linked immunosorbent assay. Study data was evaluated using appropriate statistical tests performed by the statistical program SPSS. Serum iron levels were 91±34 mcrg/dl and 75±31 mcrg/dl in N-BMI and OB children, respectively. The corresponding values for TIBC, Tf Sat %, ferritin were 265 mcrg/dl vs 299 mcrg/dl, 37.2±19.1 % vs 26.7±14.6 %, and 41±25 ng/ml vs 44±26 ng/ml. in N-BMI and OB groups, sTWEAK concentrations were measured as 351 ng/L and 325 ng/L, respectively (p>0.05). Correlation analysis revealed significant associations between sTWEAK levels and iron related parameters (p<0.05) except ferritin. In conclusion, iron contributes to apoptosis. Children with iron deficiency have decreased apoptosis rate in comparison with that of healthy children. sTWEAK is inducer of apoptosis. Obese children had lower levels of both iron and sTWEAK. Low levels of sTWEAK are associated with several types of cancers and poor survival. Although iron deficiency state was not observed in this study, the correlations detected between decreased sTWEAK and decreased iron as well as Tf Sat % values were valuable findings, which point out decreased apoptosis. This may induce a proinflammatory state, potentially leading to malignancies in the future lives of obese children.

Keywords: apoptosis, children, iron-related parameters, obesity, soluble tumor necrosis factor-like weak inducer of apoptosis

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Authors: Nilufar Chowdhury, Fereydoun Najafian Jazi, Omid Ghasemi-Fare

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The thermal effect on soil properties induces significant variations in hydraulic conductivity, which is attributable to temperature-dependent transitions in soil properties. With the elevation of temperature, there can be a notable increase in intrinsic permeability due to the degeneration of bound water molecules into a free state facilitated by thermal energy input. Conversely, thermal consolidation may cause a reduction in intrinsic permeability as soil particles undergo densification. This thermal response of soil permeability exhibits pronounced heterogeneity across different soil types. Furthermore, this temperature-induced disruption of the bound water within clay matrices can enhance the mineral-to-mineral contact, initiating irreversible deformation within the clay structure. This indicates that when soil undergoes heating-cooling cycles, plastic strain can develop, which needs to be investigated for every soil type to understand the thermo-hydro mechanical behavior of clay properly. This research aims to study the effect of the heating-cooling cycle on the intrinsic permeability and time-dependent evaluation of thermal volume change of sodium Bentonite clay. A temperature-controlled triaxial permeameter cell is used in this study. The selected temperature is 20° C, 40° C, 40° C and 80° C. The hydraulic conductivity of Bentonite clay under 100 kPa confining stresses was measured. Hydraulic conductivity analysis was performed on a saturated sample for a void ratio e = 0.9, corresponding to a dry density of 1.2 Mg/m3. Different hydraulic gradients were applied between the top and bottom of the sample to obtain a measurable flow through the sample. The hydraulic gradient used for the experiment was 4000. The diameter and thickness of the sample are 101. 6 mm, and 25.4 mm, respectively. Both for heating and cooling, the hydraulic conductivity at each temperature is measured after the flow reaches the steady state condition to make sure the volume change due to thermal loading is stabilized. Thus, soil specimens were kept at a constant temperature during both the heating and cooling phases for at least 10-18 days to facilitate the equilibration of hydraulic transients. To assess the influence of temperature-induced volume changes of Bentonite clay, the evaluation of void ratio change during this time period has been monitored. It is observed that the intrinsic permeability increases by 30-40% during the heating cycle. The permeability during the cooling cycle is 10-12% lower compared to the permeability observed during the heating cycle at a particular temperature. This reduction in permeability implies a change in soil fabric due to the thermal effect. An initial increase followed by a rapid decrease in void ratio was observed, representing the occurrence of possible osmotic swelling phenomena followed by thermal consolidation. It has been observed that after a complete heating-cooling cycle, there is a significant change in the void ratio compared to the initial void ratio of the sample. The results obtained suggest that Bentonite clay’s microstructure can change subject to a complete heating-cooling process, which regulates macro behavior such as the permeability of Bentonite clay.

Keywords: bentonite, permeability, temperature, thermal volume change

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Authors: V. T. Gerov, D. I. Gerova, I. D. Micheva, N. F. Nazifova-Tasinova, M. N. Nikolova, M. G. Pasheva, B. T. Galunska

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Multiple myeloma (MM) is the most frequent plasma cell (PC) dyscrasia that involves the skeleton. Myeloma bone disease (MBD) is characterized by osteolytic bone lesions as a result of increased osteoclasts activity not followed by reactive bone formation due to osteoblasts suppression. Skeletal complications cause significant adverse effects on quality of life and lead to increased morbidity and mortality. Last decade studies revealed the implication of different proteins in osteoclast activation and osteoblast inhibition. The aim of the present study was to determine serum levels of periostin, sRANKL and osteopontin and to evaluate their role as bone markers in MBD. Materials and methods. Thirty-two newly diagnosed MM patients (mean age: 62.2 ± 10.7 years) and 33 healthy controls (mean age: 58.9 ± 7.5 years) were enrolled in the study. According to IMWG criteria 28 patients were with symptomatic MM and 4 with monoclonal gammopathy of undetermined significance (MGUS). In respect to their bone involvement all symptomatic patients were divided into two groups (G): 9 patients with 0-3 osteolytic lesions (G1) and 19 patients with >3 osteolytic lesions and/or pathologic fractures (G2). Blood samples were drawn for routine laboratory analysis and for measurement of periostin, sRANKL and osteopontin serum levels by ELISA kits (Shanghai Sunred Biological Technology, China). Descriptive analysis, Mann-Whitney test for assessment the differences between groups and non-parametric correlation analysis were performed using GraphPad Prism v8.01. Results. The median serum levels of periostin, sRANKL and osteopontin of ММ patients were significantly higher compared to controls (554.7pg/ml (IQR=424.0-720.6) vs 396.9pg/ml (IQR=308.6-471.9), p=0.0001; 8.9pg/ml (IQR=7.1-10.5) vs 5.6pg/ml (IQR=5.1-6.4, p<0.0001 and 514.0ng/ml (IQR=469.3-754.0) vs 387.0ng/ml (IQR=335.9-441.9), p<0.0001, respectively). for assessment of differences between groups and non-parametric correlation analysis were performed using GraphPad Prism v8.01. Statistical significance was found for all tested bone markers between symptomatic MM patients and controls: G1 vs controls (p<0.03), G2 vs controls (p<0.0001) for periostin; G1 vs controls (p<0.0001), G2 vs controls (p<0.0001) for sRANKL; G1 vs controls (p=0.002), G2 vs controls (p<0.0001) for osteopontin, as well between symptomatic MM patients and MGUS patients: G1 vs MGUS (p<0.003), G2 vs MGUS (p=0.003) for periostin; G1 vs MGUS (p<0.05), G2 vs MGUS (p<0.001) for sRANKL; G1 vs MGUS (p=0.011), G2 vs MGUS (p=0.0001) for osteopontin. No differences were detected between MGUS and controls and between patients in G1 and G2 groups. Spearman correlation analysis revealed moderate positive correlation between periostin and beta-2-microglobulin (r=0.416, p=0.018), percentage bone marrow myeloma PC (r=0.432, p=0.014), and serum total protein (r=0.427, p=0.015). Osteopontin levels were also positively related to beta-2-microglobulin (r=0.540, p=0.0014), percentage bone marrow myeloma PC (r=0.423, p=0.016), and serum total protein (r=0.413, p=0.019). Serum sRANKL was only related to beta-2-microglobulin levels (r=0.398, p=0.024). Conclusion: In the present study, serum levels of periostin, sRANKL and osteopontin in newly diagnosed MM patients were evaluated. They gradually increased from MGUS to more advanced stages of MM reflecting the severity of bone destruction. These results support the idea that some new protein markers could be used in monitoring the MBD as a most severe complication of MM.

Keywords: myeloma bone disease, periostin, sRANKL, osteopontin

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Authors: John Hardy

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A range of future-oriented intelligence techniques is commonly used by states to assess their national security and develop strategies to detect and manage threats, to develop and sustain capabilities, and to recover from attacks and disasters. Although homeland security organizations use future's intelligence tools to generate scenarios and simulations which inform their planning, there have been relatively few studies of the methods available or their applications for homeland security purposes. This study presents an assessment of one category of strategic intelligence techniques, termed Multi-Path Futures Analyses (MPFA), and how it can be applied to three distinct tasks for the purpose of analyzing homeland security issues. Within this study, MPFA are categorized as a suite of analytic techniques which can include effects-based operations principles, general morphological analysis, multi-path mapping, and multi-criteria decision analysis techniques. These techniques generate multiple pathways to potential futures and thereby generate insight into the relative influence of individual drivers of change, the desirability of particular combinations of pathways, and the kinds of capabilities which may be required to influence or mitigate certain outcomes. The study assessed eighteen uses of MPFA for homeland security purposes and found that there are five key applications of MPFA which add significant value to analysis. The first application is generating measures of success and associated progress indicators for strategic planning. The second application is identifying homeland security vulnerabilities and relationships between individual drivers of vulnerability which may amplify or dampen their effects. The third application is selecting appropriate resources and methods of action to influence individual drivers. The fourth application is prioritizing and optimizing path selection preferences and decisions. The fifth application is informing capability development and procurement decisions to build and sustain homeland security organizations. Each of these applications provides a unique perspective of a homeland security issue by comparing a range of potential future outcomes at a set number of intervals and by contrasting the relative resource requirements, opportunity costs, and effectiveness measures of alternative courses of action. These findings indicate that MPFA enhances analysts’ ability to generate tangible measures of success, identify vulnerabilities, select effective courses of action, prioritize future pathway preferences, and contribute to ongoing capability development in homeland security assessments.

Keywords: homeland security, intelligence, national security, operational design, strategic intelligence, strategic planning

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Authors: Weeradej Cheewapattananuwong, Keeree Srivichian, Godchamon Somchai, Wasin Phusanong, Nontawat Yoddamnern

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Natural rubber used for traffic devices in Thailand has been developed and researched for several years. When compared with Dry Rubber Content (DRC), the quality of Rib Smoked Sheet (RSS) is better. However, the cost of admixtures, especially CaCO₃ and sulphur, is higher than the cost of RSS itself. In this research, Flexible Guideposts and Rubber Fender Barriers (RFB) are taken into consideration. In case of flexible guideposts, the materials used are both RSS and DRC60%, but for RFB, only RSS is used due to the controlled performance tests. The objective of flexible guideposts and RFB is to decrease a number of accidents, fatal rates, and serious injuries. Functions of both devices are to save road users and vehicles as well as to absorb impact forces from vehicles so as to decrease of serious road accidents. This leads to the mitigation methods to remedy the injury of motorists, form severity to moderate one. The solution is to find the best practice of traffic devices using natural rubber under the engineering concepts. In addition, the performances of materials, such as tensile strength and durability, are calculated for the modulus of elasticity and properties. In the laboratory, the simulation of crashes, finite element of materials, LRFD, and concrete technology methods are taken into account. After calculation, the trials' compositions of materials are mixed and tested in the laboratory. The tensile test, compressive test, and weathering or durability test are followed and based on ASTM. Furthermore, the Cycle-Repetition Test of Flexible Guideposts will be taken into consideration. The final decision is to fabricate all materials and have a real test section in the field. In RFB test, there will be 13 crash tests, 7 Pickup Truck tests, and 6 Motorcycle Tests. The test of vehicular crashes happens for the first time in Thailand, applying the trial and error methods; for example, the road crash test under the standard of NCHRP-TL3 (100 kph) is changed to the MASH 2016. This is owing to the fact that MASH 2016 is better than NCHRP in terms of speed, types, and weight of vehicles and the angle of crash. In the processes of MASH, Test Level 6 (TL-6), which is composed of 2,270 kg Pickup Truck, 100 kph, and 25 degree of crash-angle is selected. The final test for real crash will be done, and the whole system will be evaluated again in Korea. The researchers hope that the number of road accidents will decrease, and Thailand will be no more in the top tenth ranking of road accidents in the world.

Keywords: LRFD, load and resistance factor design, ASTM, american society for testing and materials, NCHRP, national cooperation highway research program, MASH, manual for assessing safety hardware

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Authors: Magdalena Jablonska, Andrzej Falkowski

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The negativity effect is one of the most intriguing and well-studied psychological phenomena that can be observed in many areas of human life. The aim of the following study is to investigate how valence framing and positive and negative information about political candidates affect judgments about similarity to an ideal and bad politician. Based on the theoretical framework of features of similarity, it is hypothesized that negative features have a stronger effect on similarity judgments than positive features of comparable value. Furthermore, the mediating role of affect is tested. Method: One hundred sixty-one people took part in an experimental study. Participants were divided into 6 research conditions that differed in the reference point (positive vs negative framing) and the number of favourable and unfavourable information items about political candidates (a positive, neutral and negative candidate profile). In positive framing condition, the concept of an ideal politician was primed; in the negative condition, participants were to think about a bad politician. The effect of independent variables on similarity judgments, affective evaluation, and voting intention was tested. Results: In the positive condition, the analysis showed that the negative effect of additional unfavourable features was greater than the positive effect of additional favourable features in judgements about similarity to the ideal candidate. In negative framing condition, ANOVA was insignificant, showing that neither the addition of positive features nor additional negative information had a significant impact on the similarity to a bad political candidate. To explain this asymmetry, two mediational analyses were conducted that tested the mediating role of affect in the relationship between similarity judgments and voting intention. In both situations the mediating effect was significant, but the comparison of two models showed that the mediation was stronger for a negative framing. Discussion: The research supports the negativity effect and attempts to explain the psychological mechanism behind the positive-negative asymmetry. The results of mediation analyses point to a stronger mediating role of affect in the relationship between cognitive evaluation and voting intention. Such a result suggests that negative comparisons, leading to the activation of negative features, give rise to stronger emotions than positive features of comparable strength. The findings are in line with positive-negative asymmetry, however, by adopting Tversky’s framework of features of similarity, the study integrates the cognitive mechanism of the negativity effect delineated in the contrast model of similarity with its emotional component resulting from the asymmetrical effect of positive and negative emotions on decision-making.

Keywords: affect, framing, negativity effect, positive-negative asymmetry, similarity judgements

Procedia PDF Downloads 179

Authors: John Kosmeh

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Introduction – For years, senior health care and skilled nursing facilities have been plagued with the dilemma of not having the necessary tools and equipment to adequately care for senior residents in their communities. This has led to high transport rates to emergency departments and high 30-day readmission rates, costing billions of unnecessary dollars each year, as well as quality assurance issues. Our Senior care telemedicine program is designed to solve this issue. Methods – We conducted a 1-year pilot program using our technology coupled with our 24/7 telemedicine program with skilled nursing facilities in different parts of the United States. We then compared transports rates and 30-day readmission rates to previous years before the use of our program, as well as transport rates of other communities of similar size not using our program. This data was able to give us a clear and concise look at the success rate of reducing unnecessary transport and readmissions as well as cost savings. Results – A 94% reduction nationally of unnecessary out-of-facility transports, and to date, complete elimination of 30-day readmissions. Our virtual platform allowed us to instruct facility staff on the utilization of our tools and system as well as deliver treatment by our ER-trained providers. Delay waiting for PCP callbacks was eliminated. We were able to obtain lung, heart, and abdominal ultrasound imaging, 12 lead EKG, blood labs, auscultate lung and heart sounds, and collect other diagnostic tests at the bedside within minutes, providing immediate care and allowing us to treat residents within the SNF. Are virtual capabilities allowed for loved ones, family members, and others who had medical power of attorney to virtually connect with us at the time of visit, to speak directly with the medical provider, providing increased confidence in the decision to treat the resident in-house. The decline in transports and readmissions will greatly reduce governmental cost burdens, as well as fines imposed on SNF for high 30-day readmissions, reduce the cost of Medicare A readmissions, and significantly impact the number of patients visiting overcrowded ERs. Discussion – By utilizing our program, SNF can effectively reduce the number of unnecessary transports of residents, as well as create significant savings from loss of day rates, transportation costs, and high CMS fines. The cost saving is in the thousands monthly, but more importantly, these facilities can create a higher quality of life and medical care for residents by providing definitive care instantly with ER-trained personnel.

Keywords: senior care, long term care, telemedicine, technology, senior care communities

Procedia PDF Downloads 76

Authors: Ambali Alade Odebowale, Andargachew Mekonnen Berhe, Haroldo T. Hattori, Andrey E. Miroshnichenko

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Solar thermophotovoltaic systems (STPV) have emerged as a promising solution to overcome the Shockley-Queisser limit, a significant impediment in the direct conversion of solar radiation into electricity using conventional solar cells. The STPV system comprises essential components such as an optical concentrator, selective emitter, and a thermophotovoltaic (TPV) cell. The pivotal element in achieving high efficiency in an STPV system lies in the design of a spectrally selective emitter or absorber. Traditional methods for designing and optimizing selective emitters are often time-consuming and may not yield highly selective emitters, posing a challenge to the overall system performance. In recent years, the application of machine learning techniques in various scientific disciplines has demonstrated significant advantages. This paper proposes a novel nanostructure composed of four-layered materials (SiC/W/SiO2/W) to function as a selective emitter in the energy conversion process of an STPV system. Unlike conventional approaches widely adopted by researchers, this study employs a machine learning-based approach for the design and optimization of the selective emitter. Specifically, a random forest algorithm (RFA) is employed for the design of the selective emitter, while the optimization process is executed using genetic algorithms. This innovative methodology holds promise in addressing the challenges posed by traditional methods, offering a more efficient and streamlined approach to selective emitter design. The utilization of a machine learning approach brings several advantages to the design and optimization of a selective emitter within the STPV system. Machine learning algorithms, such as the random forest algorithm, have the capability to analyze complex datasets and identify intricate patterns that may not be apparent through traditional methods. This allows for a more comprehensive exploration of the design space, potentially leading to highly efficient emitter configurations. Moreover, the application of genetic algorithms in the optimization process enhances the adaptability and efficiency of the overall system. Genetic algorithms mimic the principles of natural selection, enabling the exploration of a diverse range of emitter configurations and facilitating the identification of optimal solutions. This not only accelerates the design and optimization process but also increases the likelihood of discovering configurations that exhibit superior performance compared to traditional methods. In conclusion, the integration of machine learning techniques in the design and optimization of a selective emitter for solar thermophotovoltaic systems represents a groundbreaking approach. This innovative methodology not only addresses the limitations of traditional methods but also holds the potential to significantly improve the overall performance of STPV systems, paving the way for enhanced solar energy conversion efficiency.

Keywords: emitter, genetic algorithm, radiation, random forest, thermophotovoltaic

Procedia PDF Downloads 34

Authors: Mingming Leng

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Wal-Mart has allocated considerable human resources for its quality assurance program, in which the largest retailer serves its supply chains as a quality gatekeeper. Asda Stores Ltd., the second largest supermarket chain in Britain, is now investing £27m in significantly increasing the frequency of quality control checks in its supply chains and thus enhancing quality across its fresh food business. Moreover, Tesco, the largest British supermarket chain, already constructed a quality assessment center to carry out its gatekeeping responsibility. Motivated by the above practices, we consider a supply chain in which a retailer plays the gatekeeping role in quality assurance by identifying defects among a manufacturer's products prior to selling them to consumers. The impact of a retailer's gatekeeping activity on pricing and quality assurance in a supply chain has not been investigated in the operations management area. We draw a number of managerial insights that are expected to help practitioners judiciously consider the quality gatekeeping effort at the retail level. As in practice, when the retailer identifies a defective product, she immediately returns it to the manufacturer, who then replaces the defect with a good quality product and pays a penalty to the retailer. If the retailer does not recognize a defect but sells it to a consumer, then the consumer will identify the defect and return it to the retailer, who then passes the returned 'unidentified' defect to the manufacturer. The manufacturer also incurs a penalty cost. Accordingly, we analyze a two-stage pricing and quality decision problem, in which the manufacturer and the retailer bargain over the manufacturer's average defective rate and wholesale price at the first stage, and the retailer decides on her optimal retail price and gatekeeping intensity at the second stage. We also compare the results when the retailer performs quality gatekeeping with those when the retailer does not. Our supply chain analysis exposes some important managerial insights. For example, the retailer's quality gatekeeping can effectively reduce the channel-wide defective rate, if her penalty charge for each identified de-fect is larger than or equal to the market penalty for each unidentified defect. When the retailer imple-ments quality gatekeeping, the change in the negotiated wholesale price only depends on the manufac-turer's 'individual' benefit, and the change in the retailer's optimal retail price is only related to the channel-wide benefit. The retailer is willing to take on the quality gatekeeping responsibility, when the impact of quality relative to retail price on demand is high and/or the retailer has a strong bargaining power. We conclude that the retailer's quality gatekeeping can help reduce the defective rate for consumers, which becomes more significant when the retailer's bargaining position in her supply chain is stronger. Retailers with stronger bargaining powers can benefit more from their quality gatekeeping in supply chains.

Keywords: bargaining, game theory, pricing, quality, supply chain

Procedia PDF Downloads 258

Authors: Antònio Inês, Davide Silva, Filipa Carvalho, Luís Filipe-Riberiro, Fernando M. Nunes, Luís Abrunhosa, Fernanda Cosme

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The presence of mycotoxins in foodstuff is a matter of concern for food safety. Mycotoxins are toxic secondary metabolites produced by certain molds, being ochratoxin A (OTA) one of the most relevant. Wines can also be contaminated with these toxicants. Several authors have demonstrated the presence of mycotoxins in wine, especially ochratoxin A. Its chemical structure is a dihydro-isocoumarin connected at the 7-carboxy group to a molecule of L-β-phenylalanine via an amide bond. As these toxicants can never be completely removed from the food chain, many countries have defined levels in food in order to attend health concerns. OTA contamination of wines might be a risk to consumer health, thus requiring treatments to achieve acceptable standards for human consumption. The maximum acceptable level of OTA in wines is 2.0 μg/kg according to the Commission regulation No. 1881/2006. Therefore, the aim of this work was to reduce OTA to safer levels using different fining agents, as well as their impact on white wine physicochemical characteristics. To evaluate their efficiency, 11 commercial fining agents (mineral, synthetic, animal and vegetable proteins) were used to get new approaches on OTA removal from white wine. Trials (including a control without addition of a fining agent) were performed in white wine artificially supplemented with OTA (10 µg/L). OTA analyses were performed after wine fining. Wine was centrifuged at 4000 rpm for 10 min and 1 mL of the supernatant was collected and added of an equal volume of acetonitrile/methanol/acetic acid (78:20:2 v/v/v). Also, the solid fractions obtained after fining, were centrifuged (4000 rpm, 15 min), the resulting supernatant discarded, and the pellet extracted with 1 mL of the above solution and 1 mL of H2O. OTA analysis was performed by HPLC with fluorescence detection. The most effective fining agent in removing OTA (80%) from white wine was a commercial formulation that contains gelatin, bentonite and activated carbon. Removals between 10-30% were obtained with potassium caseinate, yeast cell walls and pea protein. With bentonites, carboxymethylcellulose, polyvinylpolypyrrolidone and chitosan no considerable OTA removal was verified. Following, the effectiveness of seven commercial activated carbons was also evaluated and compared with the commercial formulation that contains gelatin, bentonite and activated carbon. The different activated carbons were applied at the concentration recommended by the manufacturer in order to evaluate their efficiency in reducing OTA levels. Trial and OTA analysis were performed as explained previously. The results showed that in white wine all activated carbons except one reduced 100% of OTA. The commercial formulation that contains gelatin, bentonite and activated carbon reduced only 73% of OTA concentration. These results may provide useful information for winemakers, namely for the selection of the most appropriate oenological product for OTA removal, reducing wine toxicity and simultaneously enhancing food safety and wine quality.

Keywords: wine, ota removal, food safety, fining

Procedia PDF Downloads 515

Authors: Milica Lilic, Marina Rosales Martínez

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Academic research cannot be oblivious to social problems and needs, so projects that have the capacity for transformation and impact should have the opportunity to go beyond the University circles and bring benefit to society. Apart from patents and R&D research contracts, this opportunity can be achieved through entrepreneurship as one of the most direct tools to turn knowledge into a tangible product. Thus, as an example of good practices, it is intended to analyze the case of an institutional entrepreneurship program carried out at the University of Seville, aimed at researchers interested in assessing the business opportunity of their research and expanding their knowledge on procedures for the commercialization of technologies used at academic projects. The program is based on three pillars: training, teamwork sessions and networking. The training includes aspects such as product-client fit, technical-scientific and economic-financial feasibility of a spin-off, institutional organization and decision making, public and private fundraising, and making the spin-off visible in the business world (social networks, key contacts, corporate image and ethical principles). On the other hand, the teamwork sessions are guided by a mentor and aimed at identifying research results with potential, clarifying financial needs and procedures to obtain the necessary resources for the consolidation of the spin-off. This part of the program is considered to be crucial in order for the participants to convert their academic findings into a business model. Finally, the networking part is oriented to workshops about the digital transformation of a project, the accurate communication of the product or service a spin-off offers to society and the development of transferable skills necessary for managing a business. This blended program results in the final stage where each team, through an elevator pitch format, presents their research turned into a business model to an experienced jury. The awarded teams get a starting capital for their enterprise and enjoy the opportunity of formally consolidating their spin-off company at the University. Studying the results of the program, it has been shown that many researchers have basic or no knowledge of entrepreneurship skills and different ways to turn their research results into a business model with a direct impact on society. Therefore, the described program has been used as an example to highlight the importance of knowledge transfer at the University and the role that this institution should have in providing the tools to promote entrepreneurship within it. Keeping in mind that the University is defined by three main activities (teaching, research and knowledge transfer), it is safe to conclude that the latter, and the entrepreneurship as an expression of it, is crucial in order for the other two to comply with their purpose.

Keywords: good practice, knowledge transfer, a spin-off company, university

Procedia PDF Downloads 121

Authors: Dechao Meng, Yongqi Dong, Qiyuan Feng, Zhangzhang Cui, Xiang Hu, Haoliang Huang, Genhao Liang, Huanhua Wang, Hua Zhou, Hawoong Hong, Jinghua Guo, Qingyou Lu, Xiaofang Zhai, Yalin Lu

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Great efforts have been taken to reveal the intrinsic origins of emerging ferromagnetism (FM) in strained LaCoO₃ (LCO) films. However, some macro magnetic performances of LCO are still not well understood and even controversial, such as magnetic anisotropy. Determining and understanding magnetic anisotropy might help to find the true causes of FM in turn. Perpendicular magnetic anisotropy (PMA) was the first time to be directly observed in high-quality LCO films with different thickness. The in-plane (IP) and out of plane (OOP) remnant magnetic moment ratio of 30 unit cell (u.c.) films is as large as 20. The easy axis lays in the OOP direction with an IP/OOP coercive field ratio of 10. What's more, the PMA could be simply tuned by changing the thickness. With the thickness increases, the IP/OOP magnetic moment ratio remarkably decrease with magnetic easy axis changing from OOP to IP. Such a huge and tunable PMA performance exhibit strong potentials in fundamental researches or applications. What causes PMA is the first concern. More OOP orbitals occupation may be one of the micro reasons of PMA. A cluster-like magnetic domain pattern was found in 30 u.c. with no obvious color contrasts, similar to that of LaAlO₃/SrTiO₃ films. And the nanosize domains could not be totally switched even at a large OOP magnetic field of 23 T. It indicates strong IP characters or none OOP magnetism of some clusters. The IP magnetic domains might influence the magnetic performance and help to form PMA. Meanwhile some possible nonmagnetic clusters might be the reason why the measured moments of LCO films are smaller than the calculated values 2 μB/Co, one of the biggest confusions in LCO films.What tunes PMA seems much more interesting. Totally different magnetic domain patterns were found in 180 u.c. films with cluster magnetic domains surrounded by < 110 > cross-hatch lines. These lines were regarded as structure domain walls (DWs) determined by 3D reciprocal space mapping (RSM). Two groups of in-plane features with fourfold symmetry were observed near the film diffraction peaks in (002) 3D-RSM. One is along < 110 > directions with a larger intensity, which is well match the lines on the surfaces. The other is much weaker and along < 100 > directions, which is from the normal lattice titling of films deposited on cubic substrates. The < 110 > domain features obtained from (103) and (113) 3D-RSMs exhibit similar evolution of the DWs percentages and magnetic behavior. Structure domains and domain walls are believed to tune PMA performances by transform more IP magnetic moments to OOP. Last but not the least, thick films with lots of structure domains exhibit different electrical transport behaviors. A metal-to-insulator transition (MIT) and an angular dependent negative magnetic resistivity were observed near 150 K, higher than FM transition temperature but similar to that of spin-orbital coupling related 1/4 order diffraction peaks.

Keywords: structure domain, magnetic anisotropy, magnetic domain, domain wall, 3D-RSM, strain

Procedia PDF Downloads 135

Authors: P. Asiabi, M. Shahhoseini, R. Favaedi, F. Hassani, N. Nassiri, B. Movaghar, L. Karimian, P. Eftekhariyazdi

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Introduction: Polycystic Ovary Syndrome is a common gynecologic disorder. Many factors including environment, metabolism, hormones and genetics are involved in etiopathogenesis of PCOS. Of genes that have altered expression in human reproductive system disorders are HOX family genes which act as transcription factors in regulation of cell proliferation, differentiation, adhesion and migration. Since recent evidences consider epigenetic factors as causative mechanisms of PCOS, evaluation of association between known epigenetic marks of acetylation/methylation of histone 3 (H3K9ac/me) with regulatory regions of these genes can represent better insight about PCOS. In the current study, cumulus cells (CCs) which have critical roles during folliculogenesis, oocyte maturation, ovulation and fertilization were aimed to monitor epigenetic alterations of HOX genes. Material and methods: CCs were collected from 20 PCOS patients and 20 fertile women (18-36 year) with male infertility problems referred to the Royan Institute to have ICSI under GnRH antagonist protocol. Informed consents were obtained from the participants. Thirty six hours after hCG injection, ovaries were punctured and cumulus oocyte complexes were dissected. Soluble chromatin were extracted from CCs and Chromatin Immune precipitation (ChIP) coupled with Real Time PCR was performed to quantify the epigenetic marks of histone H3K9 acetylation/methylation (H3K9ac/me) on regulatory regions of 15 members of HOX genes from A-D subfamily. Results: Obtained data showed significant increase of H3K9ac epigenetic mark on regulatory regions of HOXA1, HOXB2, HOXC4, HOXD1, HOXD3 and HOXD4 (P < 0.01) and HOXC5 (P < 0.05) and also significant decrease of H3K9ac into regulatory regions of HOXA2, HOXA4, HOXA5, HOXB1 and HOXB5 (P < 0.01) and HOXB3 (P<0.05) in PCOS patients vs. control group. On the other side, there was a significant decrease in incorporation of H3K9me level on regulatory region of HOXA2, HOXA3, HOXA4, HOXA5, HOXB3 and HOXC4 (P≤0.01) and HOXB5 (P < 0.05) in PCOS patients vs. control group. This epigenetic mark (H3K9me2) has significant increase on regulatory region of HOXB1, HOXB2, HOXC5, HOXD1, HOXD3 and HOXD4 (P ≤ 0.01) and HOXB4 (P < 0.05) in patients vs. control group. There were no significant changes in acetylation/methylation levels of H3K9 on regulatory regions of the other studied genes. Conclusion: Current study suggests that epigenetic alterations of HOX genes can be correlated with PCOS and consequently female infertility. This finding might offer additional definitions of PCOS, and eventually provides insight for novel treatments with epidrugs for this disease.

Keywords: epigenetic, HOX genes, PCOS, female infertility

Procedia PDF Downloads 300

Authors: Cheila Pereira, Sara C. Cunha, Miguel A. Faria, José O. Fernandes

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The increasing world population brings several concerns, one of which is food security and sustainability. To meet this challenge, aquaculture, the farming of aquatic animals and plants, including fish, mollusks, bivalves, and algae, has experienced sustained growth and development in recent years. Recent advances in this industry have focused on reducing its economic and environmental costs, for example, the substitution of protein sources in fish feed. Plant-based proteins are now a common approach, and while it is a greener alternative to animal-based proteins, there are some disadvantages, such as their putative content and intoxicants such as mycotoxins. These are naturally occurring plant contaminants, and their exposure in fish can cause health problems, stunted growth or even death, resulting in economic losses for the producers and health concerns for the consumers. Different works have demonstrated the presence of both AFB1 (aflatoxin B1) and ENNB1 (enniatin B1) in fish feed and their capacity to be absorbed and bioaccumulate in the fish organism after digestion, further reaching humans through fish ingestion. The aim of this work was to evaluate the bioaccessibility of both mycotoxins in samples of Sparus aurata muscle using a static digestion model based on the INFOGEST protocol. The samples were subjected to different cooking procedures – raw, grilled and fried – and different seasonings – none, thyme and ginger – in order to evaluate their potential reduction effect on mycotoxins bioaccessibility, followed by the evaluation of the intestinal transport of both compounds with an in vitro cell model composed of Caco-2/HT-29 co-culture monolayers, simulating the human intestinal epithelium. The bioaccessible fractions obtained in the digestion studies were used in the transport studies for a more realistic approach to bioavailability evaluation. Results demonstrated the effect of the use of different cooking procedures and seasoning on the toxin's bioavailability. Sparus aurata was chosen in this study for its large production in aquaculture and high consumption in Europe. Also, with the continued evolution of fish farming practices and more common usage of novel feed ingredients based on plants, there is a growing concern about less studied contaminants in aquaculture and their consequences for human health. In pair with greener advances in this industry, there is a convergence towards alternative research methods, such as in vitro applications. In the case of bioavailability studies, both in vitro digestion protocols and intestinal transport assessment are excellent alternatives to in vivo studies. These methods provide fast, reliable and comparable results without ethical restraints.

Keywords: AFB1, aquaculture, bioaccessibility, ENNB1, intestinal transport.

Procedia PDF Downloads 37

Authors: Anupriya Sharma, Sapna Narula

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Over the past decade, sustainability has gone mainstream as more people are worried about environment-related issues than ever before. These issues are of even more concern for industries which leave a significant impact on the environment. Following these ecological issues, corporates are beginning to comprehend the impact on their business. Many such initiatives have been made to address these emerging issues in the consumer-driven textile industry. Demand from customers, local communities, government regulations, etc. are considered some of the major factors affecting environmental decision-making. Research also shows that motivations to go green are inevitably determined by the way top managers perceive environmental issues as managers personal values and ethical commitment act as a motivating factor towards corporate social responsibility. Little empirical research has been conducted to examine the relationship between top managers’ personal environmental attitudes and corporate environmental behaviors for the textile industry in the Indian context. The primary purpose of this study is to determine the current state of environmental management in textile industry and whether the attitude of textile firms’ top managers is significantly related to firm’s response to environmental issues and their perceived benefits of environmental management. To achieve the aforesaid objectives of the study, authors used structured questionnaire based on literature review. The questionnaire consisted of six sections with a total length of eight pages. The first section was based on background information on the position of the respondents in the organization, annual turnover, year of firm’s establishment and so on. The other five sections of the questionnaire were based upon (drivers, attitude, and awareness, sustainable business practices, barriers to implementation and benefits achieved). To test the questionnaire, a pretest was conducted with the professionals working in corporate sustainability and had knowledge about the textile industry and was then mailed to various stakeholders involved in textile production thereby covering firms top manufacturing officers, EHS managers, textile engineers, HR personnel and R&D managers. The results of the study showed that most of the textile firms were implementing some type of environmental management practice, even though the magnitude of firm’s involvement in environmental management practices varied. The results also show that textile firms with a higher level of involvement in environmental management were more involved in the process driven technical environmental practices. It also identified that firm’s top managers environmental attitudes were correlated with perceived advantages of environmental management as textile firm’s top managers are the ones who possess managerial discretion on formulating and deciding business policies such as environmental initiatives.

Keywords: attitude and awareness, Environmental management, sustainability, textile industry

Procedia PDF Downloads 218

Authors: Khadija Al-Hosni, Moon Fai Chan, Mohammed Al-Azri

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Background: Several studies suggest that most school-age adolescents are poorly informed on cancer warning signs and risk factors. Providing adolescents with sufficient knowledge would increase their awareness in adulthood and improve seeking behaviors later. Significant: The results will provide a clear vision in assisting key decision-makers in formulating policies on the students' awareness programs towards cancer. So, the likelihood of avoiding cancer in the future will be increased or even promote early diagnosis. Objectives: to evaluate the effectiveness of an education program designed to increase awareness of cancer signs and symptoms risk factors, improve the behavior of seeking help among school students in Oman, and address the barriers to obtaining medical help. Methods: A randomized controlled trial with two groups was conducted in Oman. A total of 1716 students (n=886/control, n= 830/education), aged 15-17 years, at 10th and 11th grade from 12 governmental schools 3 in governorates from 20-February-2022 to 12-May-2022. Basic demographic data were collected, and the Cancer Awareness Measure (CAM) was used as the primary outcome. Data were collected at baseline (T0) and 4 weeks after (T1). The intervention group received an education program about cancer's cause and its signs and symptoms. In contrast, the control group did not receive any education related to this issue during the study period. Non-parametric tests were used to compare the outcomes between groups. Results: At T0, the lamp was the most recognized cancer warning sign in control (55.0%) and intervention (55.2%) groups. However, there were no significant changes at T1 for all signs in the control group. In contrast, all sign outcomes were improved significantly (p<0.001) in the intervention group, the highest response was unexplained pain (93.3%). Smoking was the most recognized risk factor in both groups: (82.8% for control; 84.1% for intervention) at T0. However, there was no significant change in T1 for the control group, but there was for the intervention group (p<0.001), the highest identification was smoking cigarettes (96.5%). Too scared was the largest barrier to seeking medical help by students in the control group at T0 (63.0%) and T1 (62.8%). However, there were no significant changes in all barriers in this group. Otherwise, being too embarrassed (60.2%) was the largest barrier to seeking medical help for students in the intervention group at T0 and too scared (58.6%) at T1. Although there were reductions in all barriers, significant differences were found in six of ten only (p<0.001). Conclusion: The intervention was effective in improving students' awareness of cancer symptoms, warning signs (p<0.001), and risk factors (p<0.001 reduced the most addressed barriers to seeking medical help (p<0.001) in comparison to the control group. The Ministry of Education in Oman could integrate awareness of cancer within the curriculum, and more interventions are needed on the sociological part to overcome the barriers that interfere with seeking medical help.

Keywords: adolescents, awareness, cancer, education, intervention, student

Procedia PDF Downloads 62

Authors: Andrea L. Arnett, Ann T. Packard, Yolanda I. Garces, Kenneth W. Merrell

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Objective: Pathologic response following neoadjuvant chemoradiation (CRT) has been associated with improved overall survival (OS). Conflicting results have been reported regarding the pathologic predictive value of positron emission tomography (PET) response in patients with stage III lung cancer. The aim of this study was to evaluate the correlation between post-treatment PET response and pathologic response utilizing novel FDG-PET parameters. Methods: This retrospective study included patients with non-metastatic, stage IIIA (N2) NSCLC cancer treated with CRT followed by resection. All patients underwent PET prior to and after neoadjuvant CRT. Univariate analysis was utilized to assess correlations between PET response, nodal clearance, pCR, and near-complete pathologic response (defined as the microscopic residual disease or less). Maximal standard uptake value (SUV), standard uptake ratio (SUR) [normalized independently to the liver (SUR-L) and blood pool (SUR-BP)], metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were measured pre- and post-chemoradiation. Results: A total of 44 patients were included for review. Median age was 61.9 years, and median follow-up was 2.6 years. Histologic subtypes included adenocarcinoma (72.2%) and squamous cell carcinoma (22.7%), and the majority of patients had the T2 disease (59.1%). The rate of pCR and near-complete pathologic response within the primary lesion was 28.9% and 44.4%, respectively. The average reduction in SUVmₐₓ was 9.2 units (range -1.9-32.8), and the majority of patients demonstrated some degree of favorable treatment response. SUR-BP and SUR-L showed a mean reduction of 4.7 units (range -0.1-17.3) and 3.5 units (range –1.7-12.6), respectively. Variation in PET response was not significantly associated with histologic subtype, concurrent chemotherapy type, stage, or radiation dose. No significant correlation was found between pathologic response and absolute change in MTV or TLG. Reduction in SUVmₐₓ and SUR were associated with increased rate of pathologic response (p ≤ 0.02). This correlation was not impacted by normalization of SUR to liver versus mediastinal blood pool. A threshold of > 75% decrease in SUR-L correlated with near-complete response, with a sensitivity of 57.9% and specificity of 85.7%, as well as positive and negative predictive values of 78.6% and 69.2%, respectively (diagnostic odds ratio [DOR]: 5.6, p=0.02). A threshold of >50% decrease in SUR was also significantly associated pathologic response (DOR 12.9, p=0.2), but specificity was substantially lower when utilizing this threshold value. No significant association was found between nodal PET parameters and pathologic nodal clearance. Conclusions: Our results suggest that treatment response to neoadjuvant therapy as assessed on PET imaging can be a predictor of pathologic response when evaluated via SUV and SUR. SUR parameters were associated with higher diagnostic odds ratios, suggesting improved predictive utility compared to SUVmₐₓ. MTV and TLG did not prove to be significant predictors of pathologic response but may warrant further investigation in a larger cohort of patients.

Keywords: lung cancer, positron emission tomography (PET), standard uptake ratio (SUR), standard uptake value (SUV)

Procedia PDF Downloads 210

Authors: T. Vijay Bhasker, N. K. S Gowda, P. Krishnamoorthy, D. T. Pal, A. K. Pattanaik, A. K. Verma

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Boron (B) is a newer trace element and its biological importance and dietary essentiality is unclear in animals. The available literature suggests its putative role in bone mineralization, antioxidant status and steroid hormone synthesis. A feeding trial was conducted in Wister strain (Rattus norvegicus) albino rats for duration of 90 days. A total of 84 healthy weaned (3-4 weeks) experimental rats were randomly divided into 7 dietary groups (4 replicates of three each) viz., A (Basal diet/ Control), B (Basal diet + 5 ppm B), C (Basal diet + 10 ppm B), D (Basal diet + 20 ppm B), E (Basal diet + 40 ppm B), F (Basal diet-Ca 50%), G (Basal diet-Ca 50% + 40 ppm B). Dietary level of calcium (Ca) was maintained at two levels, 100% and 50% of requirement. Sodium borate was used as source of boron along with other ingredients of basal diet while preparing the pelletized diets. All the rats were kept in proper ventilated laboratory animal house maintained at temperature (23±2º C) and humidity (50 to 70%). At the end of experiment digestibility trial was conducted for 5 days to estimate nutrient digestibility and gut absorption of minerals. Eight rats from each group were sacrificed to collect the vital organs (liver, kidney and spleen) to study histopathology. Blood sample was drawn by heart puncture to determine biochemical profile. The average daily feed intake (g/rat/day), water intake (ml/rat/day) and body weight gain (g/rat/day) were similar among the dietary groups. The digestibility (%) of organic matter and crude fat were significantly improved (P < 0.05) was by B supplementation. The gut absorption (%) Ca was significantly increased (P < 0.01) in B supplemented groups compared to control. However, digestibility of dry matter and crude protein, gut absorption of magnesium and phosphorus showed a non-significant increasing trend with B supplementation. The gut absorption (%) of B (P < 0.01) was significantly lowered (P<0.05) in supplemented groups compared to un-supplemented ones. The serum level of triglycerides (mg/dL), HDL-cholesterol (mg/dL) and alanine transaminase (IU/L) were significantly lowered (P < 0.05) in B supplemented groups. While serum level of glucose (mg/dL) and alkaline phosphatase (KA units) showed a non-significant decreasing trend with B supplementation. However the serum levels of total cholesterol (mg/dL) and aspartate transaminase (IU/L) were similar among dietary groups. The histology sections of kidney and spleen revealed no significant changes among the dietary groups and were observed to be normal in anatomical architecture. However, the liver histology revealed cell degenerative changes with vacuolar degeneration and nuclear condensation in Ca deficient groups. But the comparative degenerative changes were mild in 40 ppm B supplemented Ca deficient group. In conclusion, dietary supplementation of graded levels of boron in rats had a positive effect on metabolism and health by improving nutrient digestibility and gut absorption of Ca. This indicates the beneficial role of dietary boron supplementation.

Keywords: boron, calcium, nutrient utilization, histopathology

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Authors: Stephen McCarthy, Joanne Gray, Esther Carr, Gerard Danjoux, Paul Baker, Rhiannon Hackett

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Background: The Go Well Health (GWH) platform is a web-based programme that allows patients to access personalised care plans and resources, aimed at prehabilitation prior to surgery. The online digital platform delivers essential patient education and support for patients prior to undergoing total hip replacements (THR) and total knee replacements (TKR). This study evaluated the impact of an online digital platform (ODP) in terms of functional health outcomes, health related quality of life and hospital length of stay following surgery. Methods: A retrospective cohort study comparing a cohort of patients who used the online digital platform (ODP) to deliver patient education and support (PES) prior to undergoing THR and TKR surgery relative to a cohort of patients who did not access the ODP and received usual care. Routinely collected Patient Reported Outcome Measures (PROMs) data was obtained on 2,406 patients who underwent a knee replacement (n=1,160) or a hip replacement (n=1,246) between 2018 and 2019 in a single surgical centre in the United Kingdom. The Oxford Hip and Knee Score and the European Quality of Life Five-Dimensional tool (EQ5D-5L) was obtained both pre-and post-surgery (at 6 months) along with hospital LOS. Linear regression was used to compare the estimate the impact of GWH on both health outcomes and negative binomial regressions were used to impact on LOS. All analyses adjusted for age, sex, Charlson Comorbidity Score and either pre-operative Oxford Hip/Knee scores or pre-operative EQ-5D scores. Fractional polynomials were used to represent potential non-linear relationships between the factors included in the regression model. Findings: For patients who underwent a knee replacement, GWH had a statistically significant impact on Oxford Knee Scores and EQ5D-5L utility post-surgery (p=0.039 and p=0.002 respectively). GWH did not have a statistically significant impact on the hospital length of stay. For those patients who underwent a hip replacement, GWH had a statistically significant impact on Oxford Hip Scores and EQ5D-5L utility post (p=0.000 and p=0.009 respectively). GWH also had a statistically significant reduction in the hospital length of stay (p=0.000). Conclusion: Health Outcomes were higher for patients who used the GWH platform and underwent THR and TKR relative to those who received usual care prior to surgery. Patients who underwent a hip replacement and used GWH also had a reduced hospital LOS. These findings are important for health policy and or decision makers as they suggest that prehabilitation via an ODP can maximise health outcomes for patients following surgery whilst potentially making efficiency savings with reductions in LOS.

Keywords: digital prehabilitation, online digital platform, orthopaedics, surgery

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Authors: Surachart Koyadun

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Introduction: Plasmodium knowlesi (P. knowlesi) malaria is a zoonotic disease that is classified as type 5 of human malaria. Commonly found in macaques (Macaca fascicularis) and (Macaca nemestrina), P. knowlesi is capable of resulting in both uncomplicated and severe malaria in humans. Situation of P. knowlesi malaria in Phang-Nga province for the past 3 years from 2020 – 2022 revealed no case report in 2020, however, a total of 14 cases had been reported in 2021 - 2022. This research aimed to 1) study the epidemiology of P. knowlesi, 2) examine the clinical manifestations of P. knowlesi patients, 3) analyze the ecology and entomology of P. knowlesi, and 4) analyze the diagnosis and treatment of P. knowlesi. Method: This research was a retrospective descriptive study/case report. The study was conducted in 14 patients with P. knowlesi malaria between 2021 and 2022 in 4 districts of Phang-Nga Province, Thailand including Thapput, Kapong, Takuapa and Khuraburi. Results: The study subjects of P. knowlesi malaria were all males. Most of them were working age groups as farmers and worked in forest or plantation areas. All had no history of blood transfusions. Most of the patients did not use mosquito nets and had a history of camping in the forest prior to the onset of fever. An analysis of all 14 sources of infection unveiled the area is home to macaques, and that area has detected Anopheles mosquito, which is the carrier of the disease. Majority of them got sick in the dry season of Thailand (December-April). The main symptoms brought to the hospital were fever, chills, headache, body aches. Laboratory findings on the first day of diagnosis were as follows: The white blood cell count was found within the normal range. In the proportion of white blood cells, eosinophils were found to be slightly higher than normal. Slight anemia was found on early examination. The platelet count was found to be below normal in all cases. Severely low platelet count (2,000 cells/mm3) was found in severe cases with multiple complications. No patient was found dead but 85.7% of complications were found, with acute renal failure being the most common. Patients with delayed diagnosis and treatment of malaria (inaccurate diagnosis or late access to the hospital) had the highest severity and complications than those who had seen the doctor since the first 3-4 days of illness or the screening of symptoms and risk history by the malaria clinic staff at vector-borne disease control unit. Conclusion and Recommendation: P. knowlesi malaria is an emerging infectious disease transmitted from animals to humans. There are challenges in epidemiology, entomology, ecology for effective surveillance, prevention and control. Early diagnosis and treatment would reduce complications and prevent death.

Keywords: malaria, plasmodium knowlesi, epidemiology, ecology, entomology, diagnosis, treatment

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Authors: Joan Casas-Roma

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Technology has become one of the main channels through which people engage in most of their everyday activities; from working to learning, or even when socializing, technology often acts as both an enabler and a mediator of such activities. Moreover, the affordances and interactions created by those technological tools determine the way in which the users interact with one another, as well as how they relate to the relevant environment, thus favoring certain kinds of actions and behaviors while discouraging others. In this regard, virtue ethics theories place a strong focus on a person's daily practice (understood as their decisions, actions, and behaviors) as the means to develop and enhance their habits and ethical competences --such as their awareness and sensitivity towards certain ethically-desirable principles. Under this understanding of ethics, this set of technologically-enabled affordances and interactions can be seen as the possibility space where the daily practice of their users takes place in a wide plethora of contexts and situations. At this point, the following question pops into mind: could these affordances and interactions be shaped in a way that would promote behaviors and habits basedonethically-desirable principles into their users? In the field of game design, the MDA framework (which stands for Mechanics, Dynamics, Aesthetics) explores how the interactions enabled within the possibility space of a game can lead to creating certain experiences and provoking specific reactions to the players. In this sense, these interactions can be shaped in ways thatcreate experiences to raise the players' awareness and sensitivity towards certain topics or principles. This research brings together the notions of technological affordances, the notions of practice and practical wisdom from virtue ethics, and the MDA framework from game design in order to explore how the possibility space created by technological interactions can be shaped in ways that enable and promote actions and behaviors supporting certain ethically-desirable principles. When shaped accordingly, interactions supporting certain ethically-desirable principlescould allow their users to carry out the kind of practice that, according to virtue ethics theories, provides the grounds to develop and enhance their awareness, sensitivity, and ethical reasoning capabilities. Moreover, and because ethical practice can happen collaterally in almost every context, decision, and action, this additional layer could potentially be applied in a wide variety of technological tools, contexts, and functionalities. This work explores the theoretical background, as well as the initial considerations and steps that would be needed in order to harness the potential ethically-desirable benefits that technology can bring, once it is understood as the space where most of their users' daily practice takes place.

Keywords: ethics, design methodology, human-computer interaction, philosophy of technology

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Authors: Opemiposi Adegbulu

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The research investigates the existence of a public interest consideration or rationale for the management of directors’ conflicts of interest within large public corporations. This is conducted through extensive literature review and theories on the definition of conflicts of interest, the firm and purposes of the fiduciary duty of loyalty under which the management of these conflicts of interest find their foundation. Conflicts of interest is an elusive, diverse and engaging subject, a cross-cutting problem of governance which involves all levels of governance, ranging from local to global, public to corporate or financial sectors. It is a common issue that affects corporate governance and corporate culture, having a negative impact on the reputation of corporations and their trustworthiness. It is clear that addressing this issue is imperative for good governance of corporations as they are increasingly becoming and are powerful global economies with significant power and influence in the society. Similarly, the bargaining power of these powerful corporations has been recognised by international organisations such as the UN and the OECD. This is made evident by the increasing calls and push for greater responsibility of these corporations for environmental and social disasters caused by their corporate activities and their impact in various parts of the world. Equally, in the US, the Sarbanes-Oxley Act like other legislation and regulatory efforts made to manage conflicts of interest linked to corporate governance, in many countries indicates that there is a (global) public interest in the maintenance of the orderly functioning of commerce. Consequently, the governance of these corporations is tremendously pivotal to the society as it touches upon a key aspect of the good functioning of society. This is because corporations, particularly large international corporations can be said to be the plumbing of the global economy. This study will employ theoretical, doctrinal and comparative methods. The research will make use largely of theory-guided methodology and theoretical framework – theories of the firm, public interest, regulation, conflicts of interest in general, directors’ conflicts of interest and corporate governance. Although, the research is intended to be narrowed down to the topic of conflicts of interest in corporate governance, the subject of company directors’ duty of loyalty and the management of conflicts of interest, an examination of the history, origin and typology of conflicts of interest in general will be carried out in order to identify some specific challenges to understanding and identifying these conflicts of interest; origin, diverging theories, psychological barrier to definition, similarities with public sector conflicts of interest due to the notions of corrosion of trust, the effect on decision-making and judgment, “being in a particular kind of situation”, etc. The result of this research will be useful and relevant in the identification of the rationale for the management of directors’ conflicts of interest, contributing to the understanding of conflicts of interest in the private sector and the significance of public interest in corporate governance of large corporations.

Keywords: conflicts of interest, corporate governance, corporate law, directors duty of loyalty, public interest

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Authors: Prince Kumar, Shamseer Kulangara Kandi, Diwan S. Rawat, Kasturi Mukhopadhyay

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Staphylococcus aureus is the most pathogenic of all staphylococci, a major cause of nosocomial infections, and known for acquiring resistance towards various commonly used antibiotics. Due to the widespread use of synthetic drugs, clinicians are now facing a serious threat in healthcare. The increasing resistance in staphylococci has created a need for alternatives to these synthetic drugs. One of the alternatives is a natural plant-based medicine for both disease prevention as well as the treatment of chronic diseases. Among such natural compounds, curcumin is one of the most studied molecules and has been an integral part of traditional medicines and Ayurveda from ancient times. It is a natural polyphenolic compound with diverse pharmacological effects, including anti-inflammatory, antioxidant, anti-cancerous and antibacterial activities. In spite of its efficacy and potential, curcumin has not been approved as a therapeutic agent yet, because of its low solubility, low bioavailability, and rapid metabolism in vivo. The presence of central β-diketone moiety in curcumin is responsible for its rapid metabolism. To overcome this, in the present study, curcuminoids were designed by modifying the central β-diketone moiety of curcumin into mono carbonyl moiety and their antibacterial potency against S. aureus ATCC 29213 was determined. Further, the mode of action and hemolytic activity of the most potent curcuminoids were studied. Minimum inhibitory concentration (MIC) and in vitro killing kinetics were used to study the antibacterial activity of the designed curcuminoids. For hemolytic assay, mouse Red blood cells were incubated with curcuminoids and hemoglobin release was measured spectrophotometrically. The mode of action of curcuminoids was analysed by membrane depolarization assay using membrane potential sensitive dye 3,3’-dipropylthiacarbocyanine iodide (DiSC3(5)) through spectrofluorimetry and membrane permeabilization assay using calcein-AM through flow cytometry. Antibacterial screening of the designed library (61 curcuminoids) revealed excellent in vitro potency of six compounds against S. aureus (MIC 8 to 32 µg/ml). Moreover, these six compounds were found to be non-hemolytic up to 225 µg/ml that is much higher than their corresponding MIC values. The in vitro killing kinetics data showed five of these lead compounds to be bactericidal causing >3 log reduction in the viable cell count within 4 hrs at 5 × MIC while the sixth compound was found to be bacteriostatic. Depolarization assay revealed that all the six curcuminoids caused depolarization in their corresponding MIC range. Further, the membrane permeabilization assay showed that all the six curcuminoids caused permeabilization at 5 × MIC in 2 hrs. This membrane depolarization and permeabilization caused by curcuminoids found to be in correlation with their corresponding killing efficacy. Both these assays point out that membrane perturbations might be a primary mode of action for these curcuminoids. Overall, the present study leads us six water soluble, non-hemolytic, membrane-active curcuminoids and provided an impetus for further research on therapeutic use of these lead curcuminoids against S. aureus.

Keywords: antibacterial, curcumin, minimum inhibitory concentration , Staphylococcus aureus

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