Search results for: observed heterozygosity

Authors: Yazan S. Khaled, Shazana Shamsuddin, Jim Tiernan, Mike McPherson, Thomas Hughes, Paul Millner, David G. Jayne

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Introduction: There is a need for real-time imaging of colorectal cancer (CRC) to allow tailored surgery to the disease stage. Fluorescence guided laparoscopic imaging of primary colorectal cancer and the draining lymphatics would potentially bring stratified surgery into clinical practice and realign future CRC management to the needs of patients. Fluorescent nanoparticles can offer many advantages in terms of intra-operative imaging and therapy (theranostic) in comparison with traditional soluble reagents. Nanoparticles can be functionalised with diverse reagents and then targeted to the correct tissue using an antibody or Affimer (artificial binding protein). We aimed to develop and test fluorescent silica nanoparticles and targeted against CRC using an anti-carcinoembryonic antigen (CEA) Affimer (Aff). Methods: Anti-CEA and control Myoglobin Affimer binders were subcloned into the expressing vector pET11 followed by transformation into BL21 Star™ (DE3) E.coli. The expression of Affimer binders was induced using 0.1 mM isopropyl β-D-1-thiogalactopyranoside (IPTG). Cells were harvested, lysed and purified using nickle chelating affinity chromatography. The photosensitiser Foslip (soluble analogue of 5,10,15,20-Tetra(m-hydroxyphenyl) chlorin) was incorporated into the core of silica nanoparticles using water-in-oil microemulsion technique. Anti-CEA or control Affs were conjugated to silica nanoparticles surface using sulfosuccinimidyl-4-(N-maleimidomethyl) cyclohexane-1-carboxylate (sulfo SMCC) chemical linker. Binding of CEA-Aff or control nanoparticles to colorectal cancer cells (LoVo, LS174T and HC116) was quantified in vitro using confocal microscopy. Results: The molecular weights of the obtained band of Affimers were ~12.5KDa while the diameter of functionalised silica nanoparticles was ~80nm. CEA-Affimer targeted nanoparticles demonstrated 9.4, 5.8 and 2.5 fold greater fluorescence than control in, LoVo, LS174T and HCT116 cells respectively (p < 0.002) for the single slice analysis. A similar pattern of successful CEA-targeted fluorescence was observed in the maximum image projection analysis, with CEA-targeted nanoparticles demonstrating 4.1, 2.9 and 2.4 fold greater fluorescence than control particles in LoVo, LS174T, and HCT116 cells respectively (p < 0.0002). There was no significant difference in fluorescence for CEA-Affimer vs. CEA-Antibody targeted nanoparticles. Conclusion: We are the first to demonstrate that Foslip-doped silica nanoparticles conjugated to anti-CEA Affimers via SMCC allowed tumour cell-specific fluorescent targeting in vitro, and had shown sufficient promise to justify testing in an animal model of colorectal cancer. CEA-Affimer appears to be a suitable targeting molecule to replace CEA-Antibody. Targeted silica nanoparticles loaded with Foslip photosensitiser is now being optimised to drive photodynamic killing, via reactive oxygen generation.

Keywords: colorectal cancer, silica nanoparticles, Affimers, antibodies, imaging

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Authors: Rodrigo Calili, Anna Carolina Sermarini, João Henrique Azevedo, Vanessa Cardoso de Albuquerque, Felipe Gonçalves, Gilberto Jannuzzi

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The diffusion of Distributed Energy Resources (DER) has caused structural changes in the relationship between consumers and electrical systems. The Photovoltaic Distributed Generation (PVDG), in particular, is an essential strategy for achieving the 2030 Agenda goals, especially SDG 7 and SDG 13. However, it is observed that most projects involving this technology in Brazil are restricted to the wealthiest classes of society, not yet reaching the low-income population, aligned with theories of energy justice. Considering the research for energy equality, one of the policies adopted by governments is the social electricity tariff (SET), which provides discounts on energy tariffs/bills. However, just granting this benefit may not be effective, and it is possible to merge it with DER technologies, such as the PVDG. Thus, this work aims to evaluate the economic viability of the policy to replace the social electricity tariff (the current policy aimed at the low-income population in Brazil) by PVDG projects. To this end, a proprietary methodology was developed that included: mapping the stakeholders, identifying critical variables, simulating policy options, and carrying out an analysis in the Brazilian context. The simulation answered two key questions: in which municipalities low-income consumers would have lower bills with PVDG compared to SET; which consumers in a given city would have increased subsidies, which are now provided for solar energy in Brazil and for the social tariff. An economic model was created for verifying the feasibility of the proposed policy in each municipality in the country, considering geographic issues (tariff of a particular distribution utility, radiation from a specific location, etc.). To validate these results, four sensitivity analyzes were performed: variation of the simultaneity factor between generation and consumption, variation of the tariff readjustment rate, zeroing CAPEX, and exemption from state tax. The behind-the-meter modality of generation proved to be more promising than the construction of a shared plant. However, although the behind-the-meter modality presents better results than the shared plant, there is a greater complexity in adopting this modality due to issues related to the infrastructure of the most vulnerable communities (e.g., precarious electrical networks, need to reinforce roofs). Considering the shared power plant modality, many opportunities are still envisaged since the risk of investing in such a policy can be mitigated. Furthermore, this modality can be an alternative due to the mitigation of the risk of default, as it allows greater control of users and facilitates the process of operation and maintenance. Finally, it was also found, that in some regions of Brazil, the continuity of the SET presents more economic benefits than its replacement by PVDG. However, the proposed policy offers many opportunities. For future works, the model may include other parameters, such as cost with low-income populations’ engagement, and business risk. In addition, other renewable sources of distributed generation can be studied for this purpose.

Keywords: low income, subsidy policy, distributed energy resources, energy justice

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Authors: Mustafa Metin Donma

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Metabolic syndrome (MetS) is characterized by a series of biochemical, physiological and anthropometric indicators and is a life-threatening health problem due to its close association with chronic diseases such as diabetes mellitus, hypertension, cancer and cardiovascular diseases. The syndrome deserves great interest both in adults and children. Central obesity is the indispensable component of MetS. Particularly, children, who are morbidly obese have a great tendency to develop the disease, because they are under the threat in their future lives. Preventive measures at this stage should be considered. For this, investigators seek for an informative scale or an index for the purpose. So far, several, but not many suggestions come into the stage. However, the diagnostic decision is not so easy and may not be complete particularly in the pediatric population. The aim of the study was to develop a MetS index capable of predicting MetS, while children are at the morbid obesity stage. This study was performed on morbid obese (MO) children, which were divided into two groups. Morbid obese children, who do not possess MetS criteria comprised the first group (n=44). The second group was composed of children (n=42) with MetS diagnosis. Parents were informed about the signed consent forms, which are required for the participation of their children in the study. The approval of the study protocol was taken from the institutional ethics committee of Tekirdag Namik Kemal University. Helsinki Declaration was accepted prior to and during the study. Anthropometric measurements including weight, height, waist circumference (WC), hip C, head C, neck C, biochemical tests including fasting blood glucose (FBG), insulin (INS), triglycerides (TRG), high density lipoprotein cholesterol (HDL-C) and blood pressure measurements (systolic (SBP) and diastolic (DBP)) were performed. Body fat percentage (BFP) values were determined by TANITA’s Bioelectrical Impedance Analysis technology. Body mass index and MetS indices were calculated. The equations for MetS index (MetSI) and advanced Donma MetS index (ADMI) were [(INS/FBG)/(HDL-C/TRG)]*100 and MetSI*[(SBP+DBP/Height)], respectively. Descriptive statistics including median values, compare means tests, correlation-regression analysis were performed within the scope of data evaluation using the statistical package program, SPSS. Statistically significant mean differences were determined by a p value smaller than 0.05. Median values for MetSI and ADMI in MO (MetS-) and MO (MetS+) groups were calculated as (25.9 and 36.5) and (74.0 and 106.1), respectively. Corresponding mean±SD values for BFPs were 35.9±7.1 and 38.2±7.7 in groups. Correlation analysis of these two indices with corresponding general BFP values exhibited significant association with ADMI, close to significance with MetSI in MO group. Any significant correlation was found with neither of the indices in MetS group. In conclusion, important associations observed with MetS indices in MO group were quite meaningful. The presence of these associations in MO group was important for showing the tendency towards the development of MetS in MO (MetS-) participants. The other index, ADMI, was more helpful for predictive purpose.

Keywords: body fat percentage, child, index, metabolic syndrome, obesity

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Authors: Makhan Maharjan, Mani Ulaganathan, Vanchiappan Aravindan, Srinivasan Madhavi, Jing-Yuan Wang, Tuti Mariana Lim

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There is great interest to exploit sustainable, low-cost, renewable resources as carbon precursors for energy storage applications. Research on development of energy storage devices has been growing rapidly due to mismatch in power supply and demand from renewable energy sources This paper reported the synthesis of porous activated carbon from biomass waste and evaluated its performance in supercapicators. In this work, we employed orange peel (waste material) as the starting material and synthesized activated carbon by pyrolysis of KOH impregnated orange peel char at 800 °C in argon atmosphere. The resultant orange peel-derived activated carbon (OP-AC) exhibited a high BET surface area of 1,901 m2 g-1, which is the highest surface area so far reported for the orange peel. The pore size distribution (PSD) curve exhibits the pores centered at 11.26 Å pore width, suggesting dominant microporosity. The OP-AC was studied as positive electrode in combination with different negative electrode materials, such as pre-lithiated graphite (LiC6) and Li4Ti5O12 for making different hybrid capacitors. The lithium ion capacitor (LIC) fabricated using OP-AC with pre-lithiated graphite delivered a high energy density of ~106 Wh kg–1. The energy density for OP-AC||Li4Ti5O12 capacitor was ~35 Wh kg–1. For comparison purpose, configuration of OP-AC||OP-AC capacitors were studied in both aqueous (1M H2SO4) and organic (1M LiPF6 in EC-DMC) electrolytes, which delivered the energy density of 6.6 Wh kg-1 and 16.3 Wh kg-1, respectively. The cycling retentions obtained at current density of 1 A g–1 were ~85.8, ~87.0 ~82.2 and ~58.8% after 2500 cycles for OP-AC||OP-AC (aqueous), OP-AC||OP-AC (organic), OP-AC||Li4Ti5O12 and OP-AC||LiC6 configurations, respectively. In addition, characterization studies were performed by elemental and proximate composition, thermogravimetry, field emission-scanning electron microscopy, Raman spectra, X-ray diffraction (XRD) pattern, Fourier transform-infrared, X-ray photoelectron spectroscopy (XPS) and N2 sorption isotherms. The morphological features from FE-SEM exhibited well-developed porous structures. Two typical broad peaks observed in the XRD framework of the synthesized carbon implies amorphous graphitic structure. The ratio of 0.86 for ID/IG in Raman spectra infers high degree of graphitization in the sample. The band spectra of C 1s in XPS display the well resolved peaks related to carbon atoms in various chemical environments; for instances, the characteristics binding energies appeared at ~283.83, ~284.83, ~286.13, ~288.56, and ~290.70 eV which correspond to sp2 -graphitic C, sp3 -graphitic C, C-O, C=O and π-π*, respectively. Characterization studies revealed the synthesized carbon to be promising electrode material towards the application for energy storage devices. The findings opened up the possibility of developing high energy LICs from abundant, low-cost, renewable biomass waste.

Keywords: lithium-ion capacitors, orange peel, pre-lithiated graphite, supercapacitors

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Authors: Sadi Ali, Yaser Kishawi

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As part of Palestine, Gaza Strip (365 km2 and 1.8 million habitants) is considered a semi-arid zone relies solely on the Coastal Aquifer. The coastal aquifer is only source of water with only 5-10% suitable for human use. This barely cover the domestic and agricultural needs of Gaza Strip. Palestinian Water Authority Strategy is to find non-conventional water resource from treated wastewater to irrigate 1500 hectares and serves over 100,000 inhabitants. A new WWTP project is to replace the old-overloaded Biet Lahia WWTP. The project consists of three parts; phase A (pressure line & 9 infiltration basins - IBs), phase B (a new WWTP) and phase C (Recovery and Reuse Scheme – RRS – to capture the spreading plume). Currently, phase A is functioning since Apr 2009. Since Apr 2009, a monitoring plan is conducted to monitor the infiltration rate (I.R.) of the 9 basins. Nearly 23 million m3 of partially treated wastewater were infiltrated up to Jun 2014. It is important to maintain an acceptable rate to allow the basins to handle the coming quantities (currently 10,000 m3 are pumped an infiltrated daily). The methodology applied was to review and analysis the collected data including the I.R.s, the WW quality and the drying-wetting schedule of the basins. One of the main findings is the relation between the Total Suspended Solids (TSS) at BLWWTP and the I.R. at the basins. Since April 2009, the basins scored an average I.R. of about 2.5 m/day. Since then the records showed a decreasing pattern of the average rate until it reached the lower value of 0.42 m/day in Jun 2013. This was accompanied with an increase of TSS (mg/L) concentration at the source reaching above 200 mg/L. The reducing of TSS concentration directly improved the I.R. (by cleaning the WW source ponds at Biet Lahia WWTP site). This was reflected in an improvement in I.R. in last 6 months from 0.42 m/day to 0.66 m/day then to nearly 1.0 m/day as the average of the last 3 months of 2013. The wetting-drying scheme of the basins was observed (3 days wetting and 7 days drying) besides the rainfall rates. Despite the difficulty to apply this scheme accurately a control of flow to each basin was applied to improve the I.R. The drying-wetting system affected the I.R. of individual basins, thus affected the overall system rate which was recorded and assessed. Also the ploughing activities at the infiltration basins as well were recommended at certain times to retain a certain infiltration level. This breaks the confined clogging layer which prevents the infiltration. It is recommended to maintain proper quality of WW infiltrated to ensure an acceptable performance of IBs. The continual maintenance of settling ponds at BLWWTP, continual ploughing of basins and applying soil treatment techniques at the IBs will improve the I.R.s. When the new WWTP functions a high standard effluent quality (TSS 20mg, BOD 20 mg/l and TN 15 mg/l) will be infiltrated, thus will enhance I.R.s of IBs due to lower organic load.

Keywords: SAT, wastewater quality, soil remediation, North Gaza

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Authors: Eszter Repasi, Akos Koller

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Our genetic information determines our look, physiology, sports performance and all our features. Maximizing the performances of athletes have adopted a science-based approach to the nutritional support. Nowadays genetics studies have blended with nutritional sciences, and a dynamically evolving, new research field have appeared. Nutritional genomics is needed to be used by nutritional experts. This is a recent field of nutritional science, which can provide a solution to reach the best sport performance using correlations between the athlete’s genome, nutritions, molecules, included human microbiome (links between food, microbiome and epigenetics), nutrigenomics and nutrigenetics. Nutritional genomics has a tremendous potential to change the future of dietary guidelines and personal recommendations. Experts need to use new technology to get information about the athletes, like nutritional genomics profile (included the determination of the oral and gut microbiome and DNA coded reaction for food components), which can modify the preparation term and sports performance. The influence of nutrients on the genes expression is called Nutrigenomics. The heterogeneous response of gene variants to nutrients, dietary components is called Nutrigenetics. The human microbiome plays a critical role in the state of health and well-being, and there are more links between food or nutrition and the human microbiome composition, which can develop diseases and epigenetic changes as well. A nutritional genomics-based profile of athletes can be the best technic for a dietitian to make a unique sports nutrition diet plan. Using functional food and the right food components can be effected on health state, thus sports performance. Scientists need to determine the best response, due to the effect of nutrients on health, through altering genome promote metabolites and result changes in physiology. Nutritional biochemistry explains why polymorphisms in genes for the absorption, circulation, or metabolism of essential nutrients (such as n-3 polyunsaturated fatty acids or epigallocatechin-3-gallate), would affect the efficacy of that nutrient. Controlled nutritional deficiencies and failures, prevented the change of health state or a newly discovered food intolerance are observed by a proper medical team, can support better sports performance. It is important that the dietetics profession informed on gene-diet interactions, that may be leading to optimal health, reduced risk of injury or disease. A special medical application for documentation and monitoring of data of health state and risk factors can uphold and warn the medical team for an early action and help to be able to do a proper health service in time. This model can set up a personalized nutrition advice from the status control, through the recovery, to the monitoring. But more studies are needed to understand the mechanisms and to be able to change the composition of the microbiome, environmental and genetic risk factors in cases of athletes.

Keywords: gene-diet interaction, multidisciplinary team, microbiome, diet plan

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Authors: Elias Jemal Abdella

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The Blue Nile River is an important shared resource of Ethiopia, Sudan and also, because it is the major contributor of water to the main Nile River, Egypt. Despite the potential benefits of regional cooperation and integrated joint basin management, all three countries continue to pursue unilateral plans for development. Besides, there is great uncertainty about the likely impacts of climate change in water availability for existing as well as proposed irrigation and hydropower projects in the Blue Nile Basin. The main objective of this study is to quantitatively assess the impact of climate change on the hydrological regime of the upper Blue Nile basin, western Ethiopia. Three models were combined, a dynamic Coordinated Regional Climate Downscaling Experiment (CORDEX) regional climate model (RCM) that is used to determine climate projections for the Upper Blue Nile basin for Representative Concentration Pathways (RCPs) 4.5 and 8.5 greenhouse gas emissions scenarios for the period 2021-2050. The outputs generated from multimodel ensemble of four (4) CORDEX-RCMs (i.e., rainfall and temperature) were used as input to a Soil and Water Assessment Tool (SWAT) hydrological model which was setup, calibrated and validated with observed climate and hydrological data. The outputs from the SWAT model (i.e., projections in river flow) were used as input to a Water Evaluation and Planning (WEAP) water resources model which was used to determine the water resources implications of the changes in climate. The WEAP model was set-up to simulate three development scenarios. Current Development scenario was the existing water resource development situation, Medium-term Development scenario was planned water resource development that is expected to be commissioned (i.e. before 2025) and Long-term full Development scenario were all planned water resource development likely to be commissioned (i.e. before 2050). The projected change of mean annual temperature for period (2021 – 2050) in most of the basin are warmer than the baseline (1982 -2005) average in the range of 1 to 1.4oC, implying that an increase in evapotranspiration loss. Subbasins which already distressed from drought may endure to face even greater challenges in the future. Projected mean annual precipitation varies from subbasin to subbasin; in the Eastern, North Eastern and South western highland of the basin a likely increase of mean annual precipitation up to 7% whereas in the western lowland part of the basin mean annual precipitation projected to decrease by 3%. The water use simulation indicates that currently irrigation demand in the basin is 1.29 Bm3y-1 for 122,765 ha of irrigation area. By 2025, with new schemes being developed, irrigation demand is estimated to increase to 2.5 Bm3y-1 for 277,779 ha. By 2050, irrigation demand in the basin is estimated to increase to 3.4 Bm3y-1 for 372,779 ha. The hydropower generation simulation indicates that 98 % of hydroelectricity potential could be produced if all planned dams are constructed.

Keywords: Blue Nile River, climate change, hydropower, SWAT, WEAP

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Authors: Farhat Jabeen, Muhammad Asad

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The study assessed the curative potential of Moringa olifera seeds against copper oxide nanoparticles induced toxicity in Oreochromis mossambicus. In order to investigate the curative potential of M. olifera seeds, firstly we examine its chemical composition, secondary metabolites, and bioactive compounds including hydroxyl-cinnamic acids, flavanols and hydroxybenzoic acids through standard methods and high performance liquid chromatography. In current study, the potential sub-lethal toxic dose of CuO-NPs (0.12 mg/l) was investigated through pilot experiment and three non-lethal doses (low=32, medium=48 and high=96 mg/l) of M. olifera were selected on the basis of its LC50 value for O. mossambicus. The experimental fish, O. mossambicus (n=100 of approximately 20 g each) were procured from Manawan Fisheries Complex, Lahore, and acclimatized for two weeks in glass aquaria. Experiment was conducted in accordance with the guidelines of Institutional Animal Ethics Committee, Government College University Faisalabad, Pakistan. During acclimatization and experimental period, fish received the commercial fish feed at 2.5% body weight daily. In order to assess the curative effect of M. olifera against CuO NPs induced toxicity, O. mossambicus were randomly divided into five groups and were designated as control (C) without any treatment, positive control (G*) exposed to potential toxic dose of CuO-NPs at 0.12 mg/l, and three treated groups namely G1, G2, and G3 co-treated with 0.12 mg/l of CuO-NPs plus different doses of M. olifera seed extract at 32, 48, and 96 mg/l, respectively for 56 days. Fish were exposed to waterborne CuO NPs and M. olifera seed extract. CuO-NPs treatment was ceased after 28 days but the doses of M. olifera were continued for 56 days. Blood was taken after 28 and 56 days through caudal venipuncture. Liver and intestine were taken for oxidative stress and histological studies after 56 days. In M. olifera seeds, moisture contents, crude protein, lipids, carbohydrates and ash were recorded as 3.8, 37.83, 32.52, 46.12, and 7.75%, respectively on dry weight basis. Total energy was recorded as 627.36 kcal/100g. Qualitative analysis of M. olifera seeds showed the presence of terpenoids, saponins, flavonoids, alkaloids and phenolics, while its quantitative analysis showed the considerable amount of total phenolics, flavonoids, saponins, and alkaloids as 134.75, 170.15, 1.57, and 0.4 µg/mg, respectively. Analysis of bioactive compounds in M. olifera seeds showed the presence of hydroxy-cinnamic acids (6.07 µg/ml), flavanols (71.72 µg/ml), and hydroxyl benzoic acids (97.82 µg/ml). The results showed that M. oliefera seed extract at 48 and 56 mg/l was able to cure against the toxic effects of CuO-NPs. The significant changes were observed in G* and G1 for sero-hepatic enzymes, anti-oxidants and histological profile. The investigations of this study showed that M. olifera is a good curative agent against potential induced toxicity of CuO-NPs in O. mossambicus. The curative effect of M. olifera is attributed to the presence of higher amount of secondary metabolites and bioactive compounds. This study suggested the use of M. olifera to curate different ailments in fish and other organisms.

Keywords: CuO nanoparticles, curative, Moringa olifera, Oreochromis mossambicus

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Authors: M. A. N. Rasanjalee Perera

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The world is facing several problems due to increasing elderly population. In Sri Lanka, along with the complexity of the modern society and structural and functional changes of the family, “caring for elders” seems as an emerging social problem. This situation may intensify as the county is moving into a middle income society. Seeking higher education and related career opportunities, and urban living in modern housing are new trends, through which several problems are generated. Among many issues related with elders, “lack of accessible and appropriate facilities in their houses as well as public buildings” can be identified as a major problem. This study argues that welfare facilities provided for the elderly people, particularly in the home environment, in the country are not adequate. Modern housing features such as bathrooms, pantries, lobbies, and leisure areas etc. are questionable as to whether they match with elders’ physical and mental needs. Consequently, elders have to face domestic accidents and many other difficulties within their living environments. Records of hospitals in the country also proved this fact. Therefore, this study tries to identify how far modern houses are suited with elders’ needs. The study further questioned whether “aging” is a considerable matter when people are buying, planning and renovating houses. A randomly selected sample of 50 houses were observed and 50 persons were interviewed around the Maharagama urban area in Colombo district to obtain primary data, while relevant secondary data and information were used to have a depth analysis. The study clearly found that none of the houses included to the sample are considering elders’ needs in planning, renovating, or arranging the home. Instead, most of the families were giving priority to the rich and elegant appearance and modern facilities of the houses. Particularly, to the bathrooms, pantry, large setting areas, balcony, parking slots for two vehicles, ad parapet walls with roller-gates are the main concerns. A significant factor found here is that even though, many children of the aged are in middle age and reaching their older years at present, they do not plan their future living within a safe and comfortable home, despite that they are hoping to spent the latter part of their lives in the their current homes. This fact highlights that not only the other responsible parts of the society, but also those who are reaching their older ages are ignoring the problems of the aged. At the same time, it was found that more than 80% of old parents do not like to stay at their children’s homes as the living environments in such modern homes are not familiar or convenient for them. Due to this context, the aged in Sri Lanka may have to be alone in their own homes due to current trend of society of migrating to urban living in modern houses. At the same time, current urban families who live in modern houses may have to face adding accessible facilities in their home environment, as current modern housing facilities may not be appropriate them for a better life in their latter part of life.

Keywords: aging population, elderly care, home environment, housing facilities

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Authors: Chuyu Huang, Itsuki Minemi, Kuanlin Chen, Yuki Hirose

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It remains unclear how language speakers are able to perceive phonological contrasts that do not exist on their own. This experiment uses the vowel-length distinction in Japanese, which is phonologically contrastive and co-occurs with tonal change in some cases. For speakers whose first language does not distinguish vowel length, contrastive duration is usually misperceived, e.g., Mandarin speakers. Two alternative hypotheses for how Mandarin speakers would perceive a phonological contrast that does not exist in their language make different predictions. The stress parameter model does not have a clear prediction about the impact of tonal type. Mandarin speakers will likely be not able to perceive vowel length as well as Japanese native speakers do, but the performance might not correlate to tonal type because the prosody of their language is distinctive, which requires users to encode lexical prosody and notice subtle differences in word prosody. By contrast, cue-based phonetic models predict that Mandarin speakers may rely on pitch differences, a secondary cue, to perceive vowel length. Two groups of Mandarin speakers, including naive non-Japanese speakers and beginner learners, were recruited to participate in an AX discrimination task involving two Japanese sound stimuli that contain a phonologically contrastive environment. Participants were asked to indicate whether the two stimuli containing a vowel-length contrast (e.g., maapero vs. mapero) sound the same. The experiment was bifactorial. The first factor contrasted three syllabic positions (syllable position; initial/medial/final), as it would be likely to affect the perceptual difficulty, as seen in previous studies, and the second factor contrasted two pitch types (accent type): one with accentual change that could be distinguished with the lexical tones in Mandarin (the different condition), with the other group having no tonal distinction but only differing in vowel length (the same condition). The overall results showed that a significant main effect of accent type by applying a linear mixed-effects model (β = 1.48, SE = 0.35, p < 0.05), which implies that Mandarin speakers tend to more successfully recognize vowel-length differences when the long vowel counterpart takes on a tone that exists in Mandarin. The interaction between the accent type and the syllabic position is also significant (β = 2.30, SE = 0.91, p < 0.05), showing that vowel lengths in the different conditions are more difficult to recognize in the word-final case relative to the initial condition. The second statistical model, which compares naive speakers to beginners, was conducted with logistic regression to test the effects of the participant group. A significant difference was found between the two groups (β = 1.06, 95% CI = [0.36, 2.03], p < 0.05). This study shows that: (1) Mandarin speakers are likely to use pitch cues to perceive vowel length in a non-native language, which is consistent with the cue-based approaches; (2) an exposure effect was observed: the beginner group achieved a higher accuracy for long vowel perception, which implied the exposure effect despite the short period of language learning experience.

Keywords: cue-based perception, exposure effect, prosodic perception, vowel duration

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Authors: Elena Filova, Ondrej Kaplan, Marie Markova, Helena Dragounova, Roman Matejka, Eduard Brynda, Lucie Bacakova

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Decellularized vessels have been evaluated as small-diameter vascular prostheses. Reseeding autologous cells onto decellularized tissue prior implantation should prolong prostheses function and make them living tissues. Suitable cell types for reseeding are both endothelial cells and bone marrow-derived stem cells, with a capacity for differentiation into smooth muscle cells upon mechanical loading. Endothelial cells assure antithrombogenicity of the vessels and MSCs produce growth factors and, after their differentiation into smooth muscle cells, they are contractile and produce extracellular matrix proteins as well. Fibrin is a natural scaffold, which allows direct cell adhesion based on integrin receptors. It can be prepared autologous. Fibrin can be modified with bound growth factors, such as basic fibroblast growth factor (FGF-2) and vascular endothelial growth factor (VEGF). These modifications in turn make the scaffold more attractive for cells ingrowth into the biological scaffold. The aim of the study was to prepare thin surface-attached fibrin assemblies with bound FGF-2 and VEGF, and to evaluate growth and differentiation of bone marrow-derived mesenchymal stem cells on the fibrin (Fb) assemblies. Following thin surface-attached fibrin assemblies were prepared: Fb, Fb+VEGF, Fb+FGF2, Fb+heparin, Fb+heparin+VEGF, Fb+heparin+FGF2, Fb+heparin+FGF2+VEGF. Cell culture poly-styrene and glass coverslips were used as controls. Human MSCs (passage 3) were seeded at the density of 8800 cells/1.5 mL alpha-MEM medium with 2.5% FS and 200 U/mL aprotinin per well of a 24-well cell culture. The cells have been cultured on the samples for 6 days. Cell densities on day 1, 3, and 6 were analyzed after staining with LIVE/DEAD cytotoxicity/viability assay kit. The differentiation of MSCs is being analyzed using qPCR. On day 1, the highest density of MSCs was observed on Fb+VEGF and Fb+FGF2. On days 3 and 6, there were similar densities on all samples. On day 1, cell morphology was polygonal and spread on all sample. On day 3 and 6, MSCs growing on Fb assemblies with FGF2 became apparently elongated. The evaluation of expression of genes for von Willebrand factor and CD31 (endothelial cells), for alpha-actin (smooth muscle cells), and for alkaline phosphatase (osteoblasts) is in progress. We prepared fibrin assemblies with bound VEGF and FGF-2 that supported attachment and growth of mesenchymal stem cells. The layers are promising for improving the ingrowth of MSCs into the biological scaffold. Supported by the Technology Agency of the Czech Republic TA04011345, and Ministry of Health NT11270-4/2010, and BIOCEV – Biotechnology and Biomedicine Centre of the Academy of Sciences and Charles University” project (CZ.1.05/1.1.00/02.0109), funded by the European Regional Development Fund for their financial supports.

Keywords: fibrin assemblies, FGF-2, mesenchymal stem cells, VEGF

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Authors: Hale Kirer Silva Lecuna, Beyza Aydin

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Health is one of the main components of human capital and sustainable development, and it is very important for economic growth. Health economics, which is an indisputable part of the science of economics, has five stages in general. These are health and development, financing of health services, economic regulation in the health, allocation of resources and efficiency of health services. A well-developed and efficient health sector plays a major role by increasing the level of development of countries. The most crucial pillars of the health sector are the hospitals that are divided into public and private. The main purpose of the hospitals is to provide more efficient services. Therefore the aim is to meet patients’ satisfaction by increasing the service quality. Health-related studies in Turkey date back to the Ottoman and Seljuk Empires. In the near past, Turkey applied 'Health Sector Transformation Programs' under different titles between 2003 and 2010. Our aim in this paper is to measure how effective these transformation programs are for the health sector, to see how much they can increase the efficiency of hospitals over the years, to see the return of investments, to make comments and suggestions on the results, and to provide a new reference for the literature. Within this framework, the public and private hospitals in Balıkesir, Bilecik, Bursa, Çanakkale, Edirne, Istanbul, Kirklareli, Kocaeli, Sakarya, Tekirdağ, Yalova will be examined by using Data Envelopment Analysis (DEA) for the years between 2000 and 2019. DEA is a linear programming-based technique, which gives relatively good results in multivariate studies. DEA basically estimates an efficiency frontier and make a comparison. Constant returns to scale and variable returns to scale are two most commonly used DEA methods. Both models are divided into two as input and output-oriented. To analyze the data, the number of personnel, number of specialist physicians, number of practitioners, number of beds, number of examinations will be used as input variables; and the number of surgeries, in-patient ratio, and crude mortality rate as output variables. 11 hospitals belonging to the Marmara region were included in the study. It is seen that these hospitals worked effectively only in 7 provinces (Balıkesir, Bilecik, Bursa, Edirne, İstanbul, Kırklareli, Yalova) for the year 2001 when no transformation program was implemented. After the transformation program was implemented, for example, in 2014 and 2016, 10 hospitals (Balıkesir, Bilecik, Bursa, Çanakkale, Edirne, İstanbul, Kocaeli, Kırklareli, Tekirdağ, Yalova) were found to be effective. In 2015, ineffective results were observed for Sakarya, Tekirdağ and Yalova. However, since these values are closer to 1 after the transformation program, we can say that the transformation program has positive effects. For Sakarya alone, no effective results have been achieved in any year. When we look at the results in general, it shows that the transformation program has a positive effect on the effectiveness of hospitals.

Keywords: data envelopment analysis, efficiency, health sector, Marmara region

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Authors: Laura Kocsor, Laszlo Peter, Laszlo Kovacs, Zsolt Kis

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The aim of our research is to prepare rare-earth-doped lithium niobate (LiNbO3) nanocrystals, having only a few dopant ions in the focal point of an exciting laser beam. These samples will be used to achieve individual addressing of the dopant ions by light beams in a confocal microscope setup. One method for the preparation of nanocrystalline materials is to reduce the particle size by mechanical grinding. High-energy ball-milling was used in several works to produce nano lithium niobate. Previously, it was reported that dry high-energy ball-milling of lithium niobate in a shaker mill results in the partial reduction of the material, which leads to a balanced formation of bipolarons and polarons yielding gray color together with oxygen release and Li2O segregation on the open surfaces. In the present work we focus on preparing LiNbO3 nanocrystals by high-energy ball-milling using a Fritsch Pulverisette 7 planetary mill. Every ball-milling process was carried out in zirconia vial with zirconia balls of different sizes (from 3 mm to 0.1 mm), wet grinding with water, and the grinding time being less than an hour. Gradually decreasing the ball size to 0.1 mm, an average particle size of about 10 nm could be obtained determined by dynamic light scattering and verified by scanning electron microscopy. High-energy ball-milling resulted in sample darkening evidenced by optical absorption spectroscopy measurements indicating that the material underwent partial reduction. The unwanted lithium oxide loss decreases the Li/Nb ratio in the crystal, strongly influencing the spectroscopic properties of lithium niobate. Zirconia contamination was found in ground samples proved by energy-dispersive X-ray spectroscopy measurements; however, it cannot be explained based on the hardness properties of the materials involved in the ball-milling process. It can be understood taking into account the presence of lithium hydroxide formed the segregated lithium oxide and water during the ball-milling process, through chemically induced abrasion. The quantity of the segregated Li2O was measured by coulometric titration. During the wet milling process in the planetary mill, it was found that the lithium oxide loss increases linearly in the early phase of the milling process, then a saturation of the Li2O loss can be seen. This change goes along with the disappearance of the relatively large particles until a relatively narrow size distribution is achieved in accord with the dynamic light scattering measurements. With the 3 mm ball size and 1100 rpm rotation rate, the mean particle size achieved is 100 nm, and the total Li2O loss is about 1.2 wt.% of the original LiNbO3. Further investigations have been done to minimize the Li2O segregation during the ball-milling process. Since the Li2O loss was observed to increase with the growing total surface of the particles, the influence of ball-milling parameters on its quantity has also been studied.

Keywords: high-energy ball-milling, lithium niobate, mechanochemical reaction, nanocrystals

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Authors: K. S. Vimal, D. Bodhini, K. Ramya, N. Lakshmipriya, R. M. Anjana, V. Sudha, J. A. Lovegrove, V. Mohan, V. Radha

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Gene-lifestyle interaction studies have been carried out in various populations. However, to date there are no studies in an Asian Indian population. Hence, we examined whether lifestyle factors such as diet and physical activity modify the association between fat mass and obesity–associated (FTO) gene variants and obesity and type 2 diabetes (T2D) in an Asian Indian population. We studied 734 unrelated T2D and 884 normal glucose-tolerant (NGT) participants randomly selected from the Chennai Urban Rural Epidemiology Study (CURES) in Southern India. Obesity was defined according to the World Health Organization Asia Pacific Guidelines (non-obese, BMI < 25 kg/m2; obese, BMI ≥ 25 kg/m2). Six single nucleotide polymorphisms (SNPs) in the FTO gene (rs9940128, rs7193144, rs8050136, rs918031, rs1588413 and rs11076023) identified from recent genome-wide association studies for T2D were genotyped by polymerase chain reaction-restriction fragment length polymorphism and direct sequencing. Dietary assessment was carried out using a validated food frequency questionnaire and physical activity was based upon the self-report. Interaction analyses were performed by including the interaction terms in the model. A joint likelihood ratio test of the main SNP effects and the SNP-diet/physical activity interaction effects was used in the linear regression analyses to maximize statistical power. Statistical analyses were performed using STATA version 13. There was a significant interaction between FTO SNP rs8050136 and carbohydrate energy percentage (Pinteraction=0.04) on obesity, where the ‘A’ allele carriers of the SNP rs8050136 had 2.46 times higher risk of obesity than those with ‘CC’ genotype (P=3.0x10-5) among individuals in the highest tertile of carbohydrate energy percentage. Furthermore, among those who had lower levels of physical activity, the ‘A’ allele carriers of the SNP rs8050136 had 1.89 times higher risk of obesity than those with ‘CC’ genotype (P=4.0x10-5). We also found a borderline interaction between SNP rs11076023 and carbohydrate energy percentage (Pinteraction=0.08) on T2D, where the ‘A’ allele carriers in the highest tertile of carbohydrate energy percentage, had 1.57 times higher risk of T2D than those with ‘TT’ genotype (P=0.002). There was also a significant interaction between SNP rs11076023 and physical activity (Pinteraction=0.03) on T2D. No further significant interactions between SNPs and macronutrient intake or physical activity on obesity and T2D were observed. In conclusion, this is the first study to provide evidence for a gene-diet and gene-physical activity interaction on obesity and T2D in an Asian Indian population. These findings suggest that the association between FTO gene variants and obesity and T2D is influenced by carbohydrate intake and physical activity levels. Greater understanding of how FTO gene influences obesity and T2D through dietary and exercise interventions will advance the development of behavioral intervention and personalised lifestyle strategies predicted to reduce the development of metabolic diseases in ‘A’ allele carriers of both SNPs in this Asian Indian population.

Keywords: dietary intake, FTO, obesity, physical activity, type 2 diabetes, Asian Indian.

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Authors: Armita Ghobadi, Samantha Emerson, Seyda Ozcaliskan

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Being a bilingual involves mastery of both speech and gesture patterns in a second language (L2). We know from earlier work in first language (L1) production contexts that speech and co-speech gesture form a tightly integrated system: co-speech gesture mirrors the patterns observed in speech, suggesting an online effect of language on nonverbal representation of events in gesture during the act of speaking (i.e., “thinking for speaking”). Relatively less is known about the online effect of language on gesture in bilinguals speaking structurally different languages. The few existing studies—mostly with small sample sizes—suggests inconclusive findings: some show greater achievement of L2 patterns in gesture with more advanced L2 speech production, while others show preferences for L1 gesture patterns even in advanced bilinguals. In this study, we focus on advanced bilingual speakers of two structurally different languages (Spanish L1 with English L2) in comparison to L1 English speakers. We ask whether bilingual speakers will follow target L2 patterns not only in speech but also in gesture, or alternatively, follow L2 patterns in speech but resort to L1 patterns in gesture. We examined this question by studying speech and gestures produced by 23 advanced adult Spanish (L1)-English (L2) bilinguals (Mage=22; SD=7) and 23 monolingual English speakers (Mage=20; SD=2). Participants were shown 16 animated motion event scenes that included distinct manner and path components (e.g., "run over the bridge"). We recorded and transcribed all participant responses for speech and segmented it into sentence units that included at least one motion verb and its associated arguments. We also coded all gestures that accompanied each sentence unit. We focused on motion event descriptions as it shows strong crosslinguistic differences in the packaging of motion elements in speech and co-speech gesture in first language production contexts. English speakers synthesize manner and path into a single clause or gesture (he runs over the bridge; running fingers forward), while Spanish speakers express each component separately (manner-only: el corre=he is running; circle arms next to body conveying running; path-only: el cruza el puente=he crosses the bridge; trace finger forward conveying trajectory). We tallied all responses by group and packaging type, separately for speech and co-speech gesture. Our preliminary results (n=4/group) showed that productions in English L1 and Spanish L1 differed, with greater preference for conflated packaging in L1 English and separated packaging in L1 Spanish—a pattern that was also largely evident in co-speech gesture. Bilinguals’ production in L2 English, however, followed the patterns of the target language in speech—with greater preference for conflated packaging—but not in gesture. Bilinguals used separated and conflated strategies in gesture in roughly similar rates in their L2 English, showing an effect of both L1 and L2 on co-speech gesture. Our results suggest that online production of L2 language has more limited effects on L2 gestures and that mastery of native-like patterns in L2 gesture might take longer than native-like L2 speech patterns.

Keywords: bilingualism, cross-linguistic variation, gesture, second language acquisition, thinking for speaking hypothesis

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Authors: Archana Sharma, Vijayashree Nayak, Ashok Kumar

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Three-dimensional matrices were fabricated from blend of natural-natural polymers like carrageenan-gelatin and synthetic -natural polymers such as PEG- gelatin (PEG of different molecular weights (2,000 and 6,000) using two different crosslinkers; glutaraldehyde and EDC-NHS by cryogelation technique. Blends represented a feasible approach to design 3-D scaffolds with controllable mechanical, physical and biochemical properties without compromising biocompatibility and biodegradability. These matrices possessed interconnected porous structure, good mechanical strength, biodegradable nature, constant swelling kinetics, ability to withstand high temperature and visco-elastic behavior. Hemocompatibility of cryogel matrices was determined by coagulation assays and hemolytic activity assay which demonstrated that these cryogels have negligible effects on coagulation time and have excellent blood compatibility. In vitro biocompatibility (cell-matrix interaction) inferred good cell adhesion, proliferation, and secretion of ECM on matrices. These matrices provide a microenvironment for the growth, proliferation, differentiation and secretion of ECM of different cell types such as IMR-32, C2C12, Cos-7, rat bone marrow derived MSCs and human bone marrow MSCs. Hoechst 33342 and PI staining also confirmed that the cells were uniformly distributed, adhered and proliferated properly on the cryogel matrix. An ideal scaffold used for tissue engineering application should allow the cells to adhere, proliferate and maintain their functionality. Neurotransmitter analysis has been done which indicated that IMR-32 cells adhered, proliferated and secreted neurotransmitters when they interacted with these matrices which showed restoration of their functionality. The cell-matrix interaction up to molecular level was also evaluated so to check genotoxicity and protein expression profile which indicated that these cryogel matrices are non-genotoxic and maintained biofunctionality of cells growing on these matrices. All these cryogels, when implanted subcutaneously in balb/c mice, showed no adverse systemic or local toxicity effects at implantation site. There was no significant increase in inflammatory cell count has otherwise been observed after scaffold implantation. These cryogels are supermacroporous and this porous structure allows cell infiltration and proliferation of host cells. This showed the integration and presence of infiltrated cells into the cryogel implants. Histological analysis confirmed that the implanted cryogels do not have any adverse effect in spite of host immune system recognition at the site of implantation, on its surrounding tissues and other vital host organs. In vivo biocompatibility study after in vitro biocompatibility analysis has also concluded that these synthesized cryogels act as important biological substitutes, more adaptable and appropriate for transplantation. Thus, these cryogels showed their potential for soft tissue engineering applications.

Keywords: cryogelation, hemocompatibility, in vitro biocompatibility, in vivo biocompatibility, soft tissue engineering applications

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Authors: Sigal Portnoy, Jason Friedman, Eitan Raveh

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Introduction: Sensory substitution is possible due to the capacity of our brain to adapt to information transmitted by a synthetic receptor via an alternative sensory system. Practical sensory substitution systems are being developed in order to increase the functionality of individuals with sensory loss, e.g. amputees. For upper limb prosthetic-users the loss of tactile feedback compels them to allocate visual attention to their prosthesis. The effect of adding vibrotactile feedback (VTF) to the applied force has been studied, however its effect on the allocation if visual attention during dual-tasking and the response during misleading visual feedback have not been studied. We hypothesized that VTF will improve the performance and reduce visual attention during dual-task assignments in healthy individuals using a robotic hand and improve the performance in a standardized functional test, despite the presence of misleading visual feedback. Methods: For the dual-task paradigm, twenty healthy subjects were instructed to toggle two keyboard arrow keys with the left hand to retain a moving virtual car on a road on a screen. During the game, instructions for various activities, e.g. mix the sugar in the glass with a spoon, appeared on the screen. The subject performed these tasks with a robotic hand, attached to the right hand. The robotic hand was controlled by the activity of the flexors and extensors of the right wrist, recorded using surface EMG electrodes. Pressure sensors were attached at the tips of the robotic hand and induced VTF using vibrotactile actuators attached to the right arm of the subject. An eye-tracking system tracked to visual attention of the subject during the trials. The trials were repeated twice, with and without the VTF. Additionally, the subjects performed the modified box and blocks, hidden from eyesight, in a motion laboratory. A virtual presentation of a misleading visual feedback was be presented on a screen so that twice during the trial, the virtual block fell while the physical block was still held by the subject. Results: This is an ongoing study, which current results are detailed below. We are continuing these trials with transradial myoelectric prosthesis-users. In the healthy group, the VTF did not reduce the visual attention or improve performance during dual-tasking for the tasks that were typed transfer-to-target, e.g. place the eraser on the shelf. An improvement was observed for other tasks. For example, the average±standard deviation of time to complete the sugar-mixing task was 13.7±17.2s and 19.3±9.1s with and without the VTF, respectively. Also, the number of gaze shifts from the screen to the hand during this task were 15.5±23.7 and 20.0±11.6, with and without the VTF, respectively. The response of the subjects to the misleading visual feedback did not differ between the two conditions, i.e. with and without VTF. Conclusions: Our interim results suggest that the performance of certain activities of daily living may be improved by VTF. The substitution of visual sensory input by tactile feedback might require a long training period so that brain plasticity can occur and allow adaptation to the new condition.

Keywords: prosthetics, rehabilitation, sensory substitution, upper limb amputation

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Authors: Terrell Strayhorn

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The lack of diversity in science, technology, engineering, and mathematics (STEM) fields is a persistent and concerning issue. One contributing factor to the underrepresentation of minority groups in STEM fields is a lack of sense of belonging, which can lead to lower levels of academic engagement, motivation, and achievement. In particular, Black students have been shown to experience lower levels of sense of belonging in STEM compared to their white peers. This study aimed to explore the effects of a psychological intervention on Black students' sense of belonging in physics and math courses at historically Black colleges and universities (HBCUs) and predominantly white institutions (PWIs). The study used a randomized controlled trial design and included 305 Black undergraduate students enrolled in physics or math courses at HBCUs and PWIs in the United States. Participants were randomly assigned to either an intervention group or a control group. The intervention consisted of a brief psychological, video-based intervention designed to enhance sense of belonging, which was delivered in a single session. The control group received no intervention. The primary outcome measure was sense of belonging in physics and math courses, as assessed by a validated self-report measure. Other outcomes included academic engagement, motivation, and achievement as measured by physics and math (course) grades. Preliminary results show that the intervention has a significant positive effect on Black students' sense of belonging in physics and math courses, with a moderate effect size. The intervention also had a significant positive effect on academic engagement and motivation, but not on academic achievement. Importantly, the effects of the intervention were larger for Black students enrolled at PWIs compared to those enrolled at HBCUs. Findings, at present, suggest that a brief psychological web-based intervention can enhance Black students' sense of belonging in physics and math courses, and that the effects may be particularly strong for Black students enrolled at PWIs, although they are not negligible for Black students at HBCUs. This is an important finding given the persistent underrepresentation of Black students in STEM fields, the growing number of Black students at PWIs, and the potential for enhancing sense of belonging to improve academic outcomes and increase diversity in these fields. The study has several limitations, including a relatively small sample size and a lack of long-term follow-up. Future research could explore the generalizability of these findings to other minority groups and other STEM fields, as well as the potential for longer-term interventions to sustain and enhance the effects observed in this study. Overall, this study highlights the potential for psychological interventions to enhance sense of belonging and improve academic outcomes for Black students in STEM courses, and underscores the importance of addressing sense of belonging as a key factor in promoting diversity and equity in STEM fields.

Keywords: sense of belonging, achievement, racial equity, postsecondary education, intervention

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Authors: D. Bikiaris, M. Nerantzaki, I. Koliakou, A. Francone, N. Kehagias

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In the present study, the formation of structures in poly(lactic acid) (PLA) has been investigated with respect to producing areas of regular, superficial features with dimensions comparable to those of cells or biological macromolecules. Nanoimprint lithography, a method of pattern replication in polymers, has been used for the production of features ranging from tens of micrometers, covering areas up to 1 cm², down to hundreds of nanometers. Both micro- and nano-structures were faithfully replicated. Potentially, PLA has wide uses within biomedical fields, from implantable medical devices, including screws and pins, to membrane applications, such as wound covers, and even as an injectable polymer for, for example, lipoatrophy. The possibility of fabricating structured PLA surfaces, with structures of the dimensions associated with cells or biological macro- molecules, is of interest in fields such as cellular engineering. Imprint-based technologies have demonstrated the ability to selectively imprint polymer films over large areas resulting in 3D imprints over flat, curved or pre-patterned surfaces. Here, we compare nano-patterned with nano-patterned by nanoimprint lithography (NIL) PLA film. A silicon nanostructured stamp (provided by Nanotypos company) having positive and negative protrusions was used to pattern PLA films by means of thermal NIL. The polymer film was heated from 40°C to 60°C above its Tg and embossed with a pressure of 60 bars for 3 min. The stamp and substrate were demolded at room temperature. Scanning electron microscope (SEM) images showed good replication fidelity of the replicated Si stamp. Contact-angle measurements suggested that positive microstructuring of the polymer (where features protrude from the polymer surface) produced a more hydrophilic surface than negative micro-structuring. The ability to structure the surface of the poly(lactic acid), allied to the polymer’s post-processing transparency and proven biocompatibility. Films produced in this were also shown to enhance the aligned attachment behavior and proliferation of Wharton’s Jelly Mesenchymal Stem cells, leading to the observed growth contact guidance. The bacterial attachment patterns of some bacteria, highlighted that the nano-patterned PLA structure can reduce the propensity for the bacteria to attach to the surface, with a greater bactericidal being demonstrated activity against the Staphylococcus aureus cells. These biocompatible, micro- and nanopatterned PLA surfaces could be useful for polymer– cell interaction experiments at dimensions at, or below, that of individual cells. Indeed, post-fabrication modification of the microstructured PLA surface, with materials such as collagen (which can further reduce the hydrophobicity of the surface), will extend the range of applications, possibly through the use of PLA’s inherent biodegradability. Further study is being undertaken to examine whether these structures promote cell growth on the polymer surface.

Keywords: poly(lactic acid), nano-imprint lithography, anti-bacterial properties, PLA

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Authors: M. Pienaar, J. W. Odendaal, J. C. Smit, J. Joubert

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Simulations are commonly used to predict the bistatic radar cross section (RCS) of military targets since characterization measurements can be expensive and time consuming. It is thus important to accurately predict the bistatic RCS of targets. Computational electromagnetic (CEM) methods can be used for bistatic RCS prediction. CEM methods are divided into full-wave and asymptotic methods. Full-wave methods are numerical approximations to the exact solution of Maxwell’s equations. These methods are very accurate but are computationally very intensive and time consuming. Asymptotic techniques make simplifying assumptions in solving Maxwell's equations and are thus less accurate but require less computational resources and time. Asymptotic techniques can thus be very valuable for the prediction of bistatic RCS of electrically large targets, due to the decreased computational requirements. This study extends previous work by validating the accuracy of asymptotic techniques to predict bistatic RCS through comparison with full-wave simulations as well as measurements. Validation is done with canonical structures as well as complex realistic aircraft models instead of only looking at a complex slicy structure. The slicy structure is a combination of canonical structures, including cylinders, corner reflectors and cubes. Validation is done over large bistatic angles and at different polarizations. Bistatic RCS measurements were conducted in a compact range, at the University of Pretoria, South Africa. The measurements were performed at different polarizations from 2 GHz to 6 GHz. Fixed bistatic angles of β = 30.8°, 45° and 90° were used. The measurements were calibrated with an active calibration target. The EM simulation tool FEKO was used to generate simulated results. The full-wave multi-level fast multipole method (MLFMM) simulated results together with the measured data were used as reference for validation. The accuracy of physical optics (PO) and geometrical optics (GO) was investigated. Differences relating to amplitude, lobing structure and null positions were observed between the asymptotic, full-wave and measured data. PO and GO were more accurate at angles close to the specular scattering directions and the accuracy seemed to decrease as the bistatic angle increased. At large bistatic angles PO did not perform well due to the shadow regions not being treated appropriately. PO also did not perform well for canonical structures where multi-bounce was the main scattering mechanism. PO and GO do not account for diffraction but these inaccuracies tended to decrease as the electrical size of objects increased. It was evident that both asymptotic techniques do not properly account for bistatic structural shadowing. Specular scattering was calculated accurately even if targets did not meet the electrically large criteria. It was evident that the bistatic RCS prediction performance of PO and GO depends on incident angle, frequency, target shape and observation angle. The improved computational efficiency of the asymptotic solvers yields a major advantage over full-wave solvers and measurements; however, there is still much room for improvement of the accuracy of these asymptotic techniques.

Keywords: asymptotic techniques, bistatic RCS, geometrical optics, physical optics

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Authors: S. Raghibdoust, E. Kamari

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Research show that reduced functional hearing has a detrimental influence on the ability of an individual to establish proper phonological representations of words, since the phonological representations are claimed to mediate the conceptual processing of written words. Word processing efficiency is expected to decrease with a decrease in functional hearing. In other words, it is predicted that hearing individuals would be more capable of word processing than individuals with hearing loss, as their functional hearing works normally. Studies also demonstrate that the quality of the functional hearing affects reading comprehension via its effect on their word processing skills. In other words, better hearing facilitates the development of phonological knowledge, and can promote enhanced strategies for the recognition of written words, which in turn positively affect higher-order processes underlying reading comprehension. The aims of this study were to investigate and compare the effect of deafness on the participants’ abilities to process written words at the lexical and sentence levels through using two online and one offline reading comprehension tests. The performance of a group of 8 deaf male students (ages 8-12) was compared with that of a control group of normal hearing male students. All the participants had normal IQ and visual status, and came from an average socioeconomic background. None were diagnosed with a particular learning or motor disability. The language spoken in the homes of all participants was Persian. Two tests of word processing were developed and presented to the participants using OpenSesame software, in order to measure the speed and accuracy of their performance at the two perceptual and conceptual levels. In the third offline test of reading comprehension which comprised of semantically plausible and semantically implausible subject relative clauses, the participants had to select the correct answer out of two choices. The data derived from the statistical analysis using SPSS software indicated that hearing and deaf participants had a similar word processing performance both in terms of speed and accuracy of their responses. The results also showed that there was no significant difference between the performance of the deaf and hearing participants in comprehending semantically plausible sentences (p > 0/05). However, a significant difference between the performances of the two groups was observed with respect to their comprehension of semantically implausible sentences (p < 0/05). In sum, the findings revealed that the seriously impoverished sentence reading ability characterizing the profound deaf subjects of the present research, exhibited their reliance on reading strategies that are based on insufficient or deviant structural knowledge, in particular in processing semantically implausible sentences, rather than a failure to efficiently process written words at the lexical level. This conclusion, of course, does not mean to say that deaf individuals may never experience deficits at the word processing level, deficits that impede their understanding of written texts. However, as stated in previous researches, it sounds reasonable to assume that the more deaf individuals get familiar with written words, the better they can recognize them, despite having a profound phonological weakness.

Keywords: deafness, reading comprehension, reading strategy, word processing, subject and object relative sentences

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Authors: Laura Gleason, Sahithi Talasila, Lauren Banner, Ladan Afifi, Neda Nikbakht

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Primary cutaneous anaplastic large cell lymphoma (pcALCL) accounts for 9% of all cutaneous T-cell lymphomas. pcALCL is classically characterized as a solitary papulonodule that often enlarges, ulcerates, and can be locally destructive, but overall exhibits an indolent course with overall 5-year survival estimated to be 90%. Distinguishing pcALCL from systemic ALCL (sALCL) is essential as sALCL confers a poorer prognosis with average 5-year survival being 40-50%. Although extremely rare, there have been several cases of ALK-positive ALCL diagnosed on skin biopsy without evidence of systemic involvement, which poses several challenges in the classification, prognostication, treatment, and follow-up of these patients. Objectives: We present a case of cutaneous ALK-positive ALCL without evidence of systemic involvement, and a narrative review of the literature to further characterize that ALK-positive ALCL limited to the skin is a distinct variant with a unique presentation, history, and prognosis. A 30-year-old woman presented for evaluation of an erythematous-violaceous papule present on her right chest for two months. With the development of multifocal disease and persistent lymphadenopathy, a bone marrow biopsy and lymph node excisional biopsy were performed to assess for systemic disease. Both biopsies were unrevealing. The patient was counseled on pursuing systemic therapy consisting of Brentuximab, Cyclophosphamide, Doxorubicin, and Prednisone given the concern for sALCL. Apropos of the patient we searched for clinically evident, cutaneous ALK-positive ALCL cases, with and without systemic involvement, in the English literature. Risk factors, such as tumor location, number, size, ALK localization, ALK translocations, and recurrence, were evaluated in cases of cutaneous ALK-positive ALCL. The majority of patients with cutaneous ALK-positive ALCL did not progress to systemic disease. The majority of cases that progressed to systemic disease in adults had recurring skin lesions and cytoplasmic localization of ALK. ALK translocations did not influence disease progression. Mean time to disease progression was 16.7 months, and significant mortality (50%) was observed in those cases that progressed to systemic disease. Pediatric cases did not exhibit a trend similar to adult cases. In both the adult and pediatric cases, a subset of cutaneous-limited ALK-positive ALCL were treated with chemotherapy. All cases treated with chemotherapy did not progress to systemic disease. Apropos of an ALK-positive ALCL patient with clinical cutaneous limited disease in the histologic presence of systemic markers, we discussed the literature data, highlighting the crucial issues related to developing a clinical strategy to approach this rare subtype of ALCL. Physicians need to be aware of the overall spectrum of ALCL, including cutaneous limited disease, systemic disease, disease with NPM-ALK translocation, disease with ALK and EMA positivity, and disease with skin recurrence.

Keywords: anaplastic large cell lymphoma, systemic, cutaneous, anaplastic lymphoma kinase, ALK, ALCL, sALCL, pcALCL, cALCL

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Authors: Pedro B. Antunes, Paulo J. Ramísio

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Road runoff is a linear source of diffuse pollution that can cause significant environmental impacts. During rainfall events, pollutants from both stationary and mobile sources, which have accumulated on the road surface, are dragged through the superficial runoff. Road runoff in coastal zones may present high levels of salinity and chlorides due to the proximity of the sea and transported marine aerosols. Appearing to be correlated to this process, organic matter concentration may also be significant. This study assesses this phenomenon with the purpose of identifying the relationships between monitored water quality parameters and intrinsic site variables. To achieve this objective, an extensive monitoring program was conducted on a Portuguese coastal highway. The study included thirty rainfall events, in different weather, traffic and salt deposition conditions in a three years period. The evaluations of various water quality parameters were carried out in over 200 samples. In addition, the meteorological, hydrological and traffic parameters were continuously measured. The salt deposition rates (SDR) were determined by means of a wet candle device, which is an innovative feature of the monitoring program. The SDR, variable throughout the year, appears to show a high correlation with wind speed and direction, but mostly with wave propagation, so that it is lower in the summer, in spite of the favorable wind direction in the case study. The distance to the sea, topography, ground obstacles and the platform altitude seems to be also relevant. It was confirmed the high salinity in the runoff, increasing the concentration of the water quality parameters analyzed, with significant amounts of seawater features. In order to estimate the correlations and patterns of different water quality parameters and variables related to weather, road section and salt deposition, the study included exploratory data analysis using different techniques (e.g. Pearson correlation coefficients, Cluster Analysis and Principal Component Analysis), confirming some specific features of the investigated road runoff. Significant correlations among pollutants were observed. Organic matter was highlighted as very dependent of salinity. Indeed, data analysis showed that some important water quality parameters could be divided into two major clusters based on their correlations to salinity (including organic matter associated parameters) and total suspended solids (including some heavy metals). Furthermore, the concentrations of the most relevant pollutants seemed to be very dependent on some meteorological variables, particularly the duration of the antecedent dry period prior to each rainfall event and the average wind speed. Based on the results of a monitoring case study, in a coastal zone, it was proven that SDR, associated with the hydrological characteristics of road runoff, can contribute for a better knowledge of the runoff characteristics, and help to estimate the specific nature of the runoff and related water quality parameters.

Keywords: coastal zones, monitoring, road runoff pollution, salt deposition

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Authors: Oleg Reva, Ilya Korotetskiy, Marina Lankina, Murat Kulmanov, Aleksandr Ilin

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Molecular docking approaches are widely used for design of new antibiotics and modeling of antibacterial activities of numerous ligands which bind specifically to active centers of indispensable enzymes and/or key signaling proteins of pathogens. Widespread drug resistance among pathogenic microorganisms calls for development of new antibiotics specifically targeting important metabolic and information pathways. A generally recognized problem is that almost all molecular targets have been identified already and it is getting more and more difficult to design innovative antibacterial compounds to combat the drug resistance. A promising way to overcome the drug resistance problem is an induction of reversion of drug resistance by supplementary medicines to improve the efficacy of the conventional antibiotics. In contrast to well established computer-based drug design, modeling of drug resistance reversion still is in its infancy. In this work, we proposed an approach to identification of compensatory genetic variants reducing the fitness cost associated with the acquisition of drug resistance by pathogenic bacteria. The approach was based on an analysis of the population genetic of Mycobacterium tuberculosis and on results of experimental modeling of the drug resistance reversion induced by a new anti-tuberculosis drug FS-1. The latter drug is an iodine-containing nanomolecular complex that passed clinical trials and was admitted as a new medicine against MDR-TB in Kazakhstan. Isolates of M. tuberculosis obtained on different stages of the clinical trials and also from laboratory animals infected with MDR-TB strain were characterized by antibiotic resistance, and their genomes were sequenced by the paired-end Illumina HiSeq 2000 technology. A steady increase in sensitivity to conventional anti-tuberculosis antibiotics in series of isolated treated with FS-1 was registered despite the fact that the canonical drug resistance mutations identified in the genomes of these isolates remained intact. It was hypothesized that the drug resistance phenotype in M. tuberculosis requires an adjustment of activities of many genes to compensate the fitness cost of the drug resistance mutations. FS-1 cased an aggravation of the fitness cost and removal of the drug-resistant variants of M. tuberculosis from the population. This process caused a significant increase in genetic heterogeneity of the Mtb population that was not observed in the positive and negative controls (infected laboratory animals left untreated and treated solely with the antibiotics). A large-scale search for linkage disequilibrium associations between the drug resistance mutations and genetic variants in other genomic loci allowed identification of target proteins, which could be influenced by supplementary drugs to increase the fitness cost of the drug resistance and deprive the drug-resistant bacterial variants of their competitiveness in the population. The approach will be used to improve the efficacy of FS-1 and also for computer-based design of new drugs to combat drug-resistant infections.

Keywords: complete genome sequencing, computational modeling, drug resistance reversion, Mycobacterium tuberculosis

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Authors: Adriana Postal, Silvio C. Sampaio, Marcio A. Villas Boas, Josué P. Castro

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This study deals with the estimation of reference evapotranspiration (ET₀) in an agricultural context, focusing on efficient irrigation management to meet the growing interest in the sustainable management of water resources. Given the importance of water in agriculture and its scarcity in many regions, efficient use of this resource is essential to ensure food security and environmental sustainability. The methodology used involved the application of artificial intelligence techniques, specifically Multilayer Perceptron (MLP) Artificial Neural Networks (ANNs), to predict ET₀ in the state of Paraná, Brazil. The models were trained and validated with meteorological data from the Brazilian National Institute of Meteorology (INMET), together with data obtained from a producer's weather station in the western region of Paraná. Two optimizers (SGD and Adam) and different meteorological variables, such as temperature, humidity, solar radiation, and wind speed, were explored as inputs to the models. Nineteen configurations with different input variables were tested; amidst them, configuration 9, with 8 input variables, was identified as the most efficient of all. Configuration 10, with 4 input variables, was considered the most effective, considering the smallest number of variables. The main conclusions of this study show that MLP ANNs are capable of accurately estimating ET₀, providing a valuable tool for irrigation management in agriculture. Both configurations (9 and 10) showed promising performance in predicting ET₀. The validation of the models with cultivator data underlined the practical relevance of these tools and confirmed their generalization ability for different field conditions. The results of the statistical metrics, including Mean Absolute Error (MAE), Mean Squared Error (MSE), Root Mean Squared Error (RMSE), and Coefficient of Determination (R²), showed excellent agreement between the model predictions and the observed data, with MAE as low as 0.01 mm/day and 0.03 mm/day, respectively. In addition, the models achieved an R² between 0.99 and 1, indicating a satisfactory fit to the real data. This agreement was also confirmed by the Kolmogorov-Smirnov test, which evaluates the agreement of the predictions with the statistical behavior of the real data and yields values between 0.02 and 0.04 for the producer data. In addition, the results of this study suggest that the developed technique can be applied to other locations by using specific data from these sites to further improve ET₀ predictions and thus contribute to sustainable irrigation management in different agricultural regions. The study has some limitations, such as the use of a single ANN architecture and two optimizers, the validation with data from only one producer, and the possible underestimation of the influence of seasonality and local climate variability. An irrigation management application using the most efficient models from this study is already under development. Future research can explore different ANN architectures and optimization techniques, validate models with data from multiple producers and regions, and investigate the model's response to different seasonal and climatic conditions.

Keywords: agricultural technology, neural networks in agriculture, water efficiency, water use optimization

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Authors: Dan W. Rhodes, Juliane Hey, Magali Karagueuzian, Florianne Martinez, Yael Sandowski, Vanessa Roulet, Mahmoud Badawi, Mohammed-Amine Chakir, Valérie Simon, Jérémie Gautier, Françoise Le Boulaire, Catherine Coignard, Claire Vincent, Sandrine Greaume, Isabelle Voisin

Abstract:

Background: Beckman Coulter, Inc. (BEC) has recently developed a fully automated second-generation anti-HCV test on a new immunoassay platform. The objective of this multicenter study conducted in Europe was to evaluate the performance of the ACCESS anti-HCV assay on the recently CE-marked DxI 9000 ACCESS Immunoassay Analyzer as an aid in the diagnosis of HCV (Hepatitis C Virus) infection and as a screening test for blood and plasma donors. Methods: The clinical specificity of the ACCESS anti-HCV assay was determined using HCV antibody-negative samples from blood donors and hospitalized patients. Sample antibody status was determined by a CE-marked anti-HCV assay (Abbott ARCHITECTTM anti-HCV assay or Abbott PRISM HCV assay) with an additional confirmation method (Immunoblot testing with INNO-LIATM HCV Score - Fujirebio), if necessary, according to pre-determined testing algorithms. The clinical sensitivity was determined using known HCV antibody-positive samples, identified positive by Immunoblot testing with INNO-LIATM HCV Score - Fujirebio. HCV RNA PCR or genotyping was available on all Immunoblot positive samples for further characterization. The false initial reactive rate was determined on fresh samples from blood donors and hospitalized patients. Thirty (30) commercially available seroconversion panels were tested to assess the sensitivity for early detection of HCV infection. The study was conducted from November 2019 to March 2022. Three (3) external sites and one (1) internal site participated. Results: Clinical specificity (95% CI) was 99.7% (99.6 – 99.8%) on 5852 blood donors and 99.0% (98.4 – 99.4%) on 1527 hospitalized patient samples. There were 15 discrepant samples (positive on ACCESS anti-HCV assay and negative on both ARCHITECT and Immunoblot) observed with hospitalized patient samples, and of note, additional HCV RNA PCR results showed five (5) samples had positive HCV RNA PCR results despite the absence of HCV antibody detection by ARCHITECT and Immunoblot, suggesting a better sensitivity of the ACCESS anti-HCV assay with these five samples compared to the ARCHITECT and Immunoblot anti-HCV assays. Clinical sensitivity (95% CI) on 510 well-characterized, known HCV antibody-positive samples was 100.0% (99.3 – 100.0%), including 353 samples with known HCV genotypes (1 to 6). The overall false initial reactive rate (95% CI) on 6630 patient samples was 0.02% (0.00 – 0.09%). Results obtained on 30 seroconversion panels demonstrated that the ACCESS anti-HCV assay had equivalent sensitivity performances, with an average bleed difference since the first reactive bleed below one (1), compared to the ARCHITECTTM anti-HCV assay. Conclusion: The newly developed ACCESS anti-HCV assay from BEC for use on the DxI 9000 ACCESS Immunoassay Analyzer demonstrated high clinical sensitivity and specificity, equivalent to currently marketed anti-HCV assays, as well as a low false initial reactive rate.

Keywords: DxI 9000 ACCESS Immunoassay Analyzer, HCV, HCV antibody, Hepatitis C virus, immunoassay

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Authors: Sadi Ali, Yaser Kishawi

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As part of Palestine, Gaza Strip (365 km2 and 1.8 million habitants) is considered a semi-arid zone relies solely on the Coastal Aquifer. The coastal aquifer is only source of water with only 5-10% suitable for human use. This barely covers the domestic and agricultural needs of Gaza Strip. Palestinian Water Authority Strategy is to find non-conventional water resource from treated wastewater to irrigate 1500 hectares and serves over 100,000 inhabitants. A new WWTP project is to replace the old-overloaded Biet Lahia WWTP. The project consists of three parts; phase A (pressure line & 9 infiltration basins - IBs), phase B (a new WWTP) and phase C (Recovery and Reuse Scheme – RRS – to capture the spreading plume). Currently, phase A is functioning since Apr 2009. Since Apr 2009, a monitoring plan is conducted to monitor the infiltration rate (I.R.) of the 9 basins. Nearly 23 million m3 of partially treated wastewater were infiltrated up to Jun 2014. It is important to maintain an acceptable rate to allow the basins to handle the coming quantities (currently 10,000 m3 are pumped an infiltrated daily). The methodology applied was to review and analysis the collected data including the I.R.s, the WW quality and the drying-wetting schedule of the basins. One of the main findings is the relation between the Total Suspended Solids (TSS) at BLWWTP and the I.R. at the basins. Since April 2009, the basins scored an average I.R. of about 2.5 m/day. Since then the records showed a decreasing pattern of the average rate until it reached the lower value of 0.42 m/day in Jun 2013. This was accompanied with an increase of TSS (mg/L) concentration at the source reaching above 200 mg/L. The reducing of TSS concentration directly improved the I.R. (by cleaning the WW source ponds at Biet Lahia WWTP site). This was reflected in an improvement in I.R. in last 6 months from 0.42 m/day to 0.66 m/day then to nearly 1.0 m/day as the average of the last 3 months of 2013. The wetting-drying scheme of the basins was observed (3 days wetting and 7 days drying) besides the rainfall rates. Despite the difficulty to apply this scheme accurately a control of flow to each basin was applied to improve the I.R. The drying-wetting system affected the I.R. of individual basins, thus affected the overall system rate which was recorded and assessed. Also the ploughing activities at the infiltration basins as well were recommended at certain times to retain a certain infiltration level. This breaks the confined clogging layer which prevents the infiltration. It is recommended to maintain proper quality of WW infiltrated to ensure an acceptable performance of IBs. The continual maintenance of settling ponds at BLWWTP, continual ploughing of basins and applying soil treatment techniques at the IBs will improve the I.R.s. When the new WWTP functions a high standard effluent quality (TSS 20mg, BOD 20 mg/l, and TN 15 mg/l) will be infiltrated, thus will enhance I.R.s of IBs due to lower organic load.

Keywords: soil aquifer treatment, recovery and reuse scheme, infiltration basins, North Gaza

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Authors: Areej Al-Hamad, Yasin Yasin, Kateryna Metersky

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This mixed-method systematic review and meta-analysis provide an encompassing understanding of the barriers, facilitators, and predictors of refugee women's employment and economic inclusion. The study sheds light on the complex interplay of sociocultural, personal, political, and environmental factors influencing these outcomes, underlining the urgent need for a multifaceted, tailored approach to devising strategies, policies, and interventions aimed at boosting refugee women's economic empowerment. Our findings suggest that sociocultural factors, including gender norms, societal attitudes, language proficiency, and social networks, profoundly shape refugee women's access to and participation in the labor market. Personal factors such as age, educational attainment, health status, skills, and previous work experience also play significant roles. Political factors like immigration policies, regulations, and rights to work, alongside environmental factors like labor market conditions, availability of employment opportunities, and access to resources and support services, further contribute to the complex dynamics influencing refugee women's economic inclusion. The significant variability observed in the impacts of these factors across different contexts underscores the necessity of adopting population and region-specific strategies. A one-size-fits-all approach may prove to be ineffective due to the diversity and unique circumstances of refugee women across different geographical, cultural, and political contexts. The study's findings have profound implications for policy-making, practice, education, and research. The insights garnered a call for coordinated efforts across these domains to bolster refugee women's economic participation. In policy-making, the findings necessitate a reassessment of current immigration and labor market policies to ensure they adequately support refugee women's employment and economic integration. In practice, they highlight the need for comprehensive, tailored employment services and interventions that address the specific barriers and leverage the facilitators identified. In education, they underline the importance of language and skills training programs that cater to the unique needs and circumstances of refugee women. Lastly, in research, they emphasize the need for ongoing investigations into the multifaceted factors influencing refugee women's employment experiences, allowing for continuous refinement of our understanding and interventions. Through this comprehensive exploration, the study contributes to ongoing efforts aimed at creating more inclusive, equitable societies. By continually refining our understanding of the complex factors influencing refugee women's employment experiences, we can pave the way toward enhanced economic empowerment for this vulnerable population.

Keywords: refugee women, employment barriers, systematic review, employment facilitators

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Authors: De-Shin Liu, Po-Chun Wen, Zhen-Wei Zhuang, Hsueh-Chih Liu, Pei-Chen Huang

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Wafer probing tests play an important role in semiconductor manufacturing procedures in accordance with the yield and reliability requirement of the wafer after the backend-of-the-line process. Accordingly, the stable physical and electrical contact between the probe and the tested wafer during wafer probing is regarded as an essential issue in identifying the known good die. The probe card can be integrated with multiple probe needles, which are classified as vertical, cantilever and micro-electro-mechanical systems type probe selections. Among all potential probe types, the vertical probe has several advantages as compared with other probe types, including maintainability, high probe density and feasibility for high-speed wafer testing. In the present study, the mechanical response of the wafer probing test with the vertical cobra probe on 720 μm thick silicon (Si) substrate with a 1.4 μm thick aluminum (Al) pad is investigated by the experiment and transient dynamic simulation approach. Because the deformation mechanism of the vertical cobra probe is determined by both bending and buckling mechanisms, the stable correlation between contact forces and overdrive (OD) length must be carefully verified. Moreover, the decent OD length with corresponding contact force contributed to piercing the native oxide layer of the Al pad and preventing the probing test-induced damage on the interconnect system. Accordingly, the scratch depth of the Al pad under various OD lengths is estimated by the atomic force microscope (AFM) and simulation work. In the wafer probing test configuration, the contact phenomenon between the probe needle and the tested object introduced large deformation and twisting of mesh gridding, causing the subsequent numerical divergence issue. For this reason, the arbitrary Lagrangian-Eulerian method is utilized in the present simulation work to conquer the aforementioned issue. The analytic results revealed a slight difference when the OD is considered as 40 μm, and the simulated is almost identical to the measured scratch depths of the Al pad under higher OD lengths up to 70 μm. This phenomenon can be attributed to the unstable contact of the probe at low OD length with the scratch depth below 30% of Al pad thickness, and the contact status will be being stable when the scratch depth over 30% of pad thickness. The splash of the Al pad is observed by the AFM, and the splashed Al debris accumulates on a specific side; this phenomenon is successfully simulated in the transient dynamic simulation. Thus, the preferred testing OD lengths are found as 45 μm to 70 μm, and the corresponding scratch depths on the Al pad are represented as 31.4% and 47.1% of Al pad thickness, respectively. The investigation approach demonstrated in this study contributed to analyzing the mechanical response of wafer probing test configuration under large strain conditions and assessed the geometric designs and material selections of probe needles to meet the requirement of high resolution and high-speed wafer-level probing test for thinned wafer application.

Keywords: wafer probing test, vertical probe, probe mark, mechanical response, FEA simulation

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Authors: Katarzyna Drela, Miroslaw Wielgos, Mikolaj Wrobel, Barbara Lukomska

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Mesenchymal stem cells (MSCs) have a great potential in regenerative medicine. Since the initial number of isolated MSCs is limited, in vitro propagation is often required to reach sufficient numbers of cells for therapeutic applications. During long-term culture MSCs may undergo genetic or epigenetic alterations that subsequently increase the probability of spontaneous malignant transformation. Thus, factors that influence genomic stability of MSCs following long-term expansions need to be clarified before cultured MSCs are employed for clinical application. The aim of our study was to investigate the potential for spontaneous transformation of human neonatal cord blood (HUCB-MSCs) and adult bone marrow (BM-MSCs) derived MSCs. Materials and Methods: HUCB-MSCs and BM-MSCs were isolated by standard Ficoll gradient centrifugations method. Isolated cells were initially plated in high density 106 cells per cm2. After 48 h medium were changed and non-adherent cells were removed. The malignant transformation of MSCs in vitro was evaluated by morphological changes, proliferation rate, ability to enter cell senescence, the telomerase expression and chromosomal abnormality. Proliferation of MSCs was analyzed with WST-1 reduction method and population doubling time (PDT) was calculated at different culture stages. Then the expression pattern of genes characteristic for mesenchymal or epithelial cells, as well as transcriptions factors were examined by RT-PCR. Concomitantly, immunocytochemical analysis of gene-related proteins was employed. Results: Our studies showed that MSCs from all bone marrow isolations ultimately entered senescence and did not undergo spontaneous malignant transformation. However, HUCB-MSCs from one of the 15 donors displayed an increased proliferation rate, failed to enter senescence, and exhibited an altered cell morphology. In this sample we observed two different cell phenotypes: one mesenchymal-like exhibited spindle shaped morphology and express specific mesenchymal surface markers (CD73, CD90, CD105, CD166) with low proliferation rate, and the second one with round, densely package epithelial-like cells with significantly increased proliferation rate. The PDT of epithelial-like populations was around 1day and 100% of cells were positive for proliferation marker Ki-67. Moreover, HUCB-MSCs showed a positive expression of human telomerase reverse transcriptase (hTERT), cMYC and exhibit increased number of CFU during the long-term culture in vitro. Furthermore, karyotype analysis revealed chromosomal abnormalities including duplications. Conclusions: Our studies demonstrate that HUCB-MSCs are susceptible to spontaneous malignant transformation during long-term culture. Spontaneous malignant transformation process following in vitro culture has enormous effect on the biosafety issues of future cell-based therapies and regenerative medicine regimens.

Keywords: mesenchymal stem cells, spontaneous, transformation, long-term culture

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