Search results for: instructional design model

Authors: Elina Vroblevska, Toms Ratfelders

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This paper examines the impact of international status-seeking aspirations on great power behavior within the international system. In particular, we seek to test the assumption advanced by the proponents of the Social Identity Theory (SIT) that the inability to achieve social mobilization through joining perceived higher-status social groups (of states) leads great powers to adopt the approach of social competition in which they aim to equal or outdo the dominant group in the area on which its claim to superior status rests. Since the dissolution of the Soviet Union, Russia has struggled to be accepted as a great power by the group of Western states that had created the dominant international system order, while the Soviet states were isolated. While the 1990s and the beginning of the 21st century can be characterized by striving to integrate into the existing order, the second decade has seen a rather sharp turn towards creating a new power center for Russia through the realization of ideas of multipolarity rivalry and uniqueness of the state itself. Increasingly, we have seen the Kremlin striving to collaborate and mobilize groups of states that fall outside of the categories of democracy, multiculturalism, and international order, the way that is perceived by the dominant group, which can be described as the West. Instead, Russia builds its own narrative where it creates an alternative understanding of these values, differentiating from the higher-status social group. The Global South, from a Russian perspective, is the group of states that can still be swayed to create an alternative power center in the international system - one where Russia can assert its status as a great power. This is based on a number of reasons, the most important being that the global north is already highly institutionalized in terms of economy (the EU) and defense (NATO), leaving no room for Russia but to integrate within the existing framework. Second, the difference in values and their interpretation - Russia has been adamant, for the last twenty years, on basing its moral code on traditional values like religion, the heterosexual family model, and moral superiority, which contradict the overall secularism of the Global North. And last, the striking difference in understanding of state governance models - with Russia becoming more autocratic over the course of the last 20 years, it has deliberately created distance between itself and democratic states, entering a “gray area” of alternative understanding of democracy which is more relatable to the global South countries. Using computational text analysis of the excerpts of Vladimir Putin’s speeches delivered from 2000-2022 regarding the areas that fall outside the immediate area of interest of Russia (the Global South), we identify 80 topics that relate to the particular component of the great power status - interest to use force globally. These topics are compared across four temporal frames that capture the periods of more and less permissible Western social boundaries. We find that there exists a negative association between such permissiveness and Putin’s emphasis on the “use of force” topics. This lends further support to the Social Identity Theory and contributes to broadening its applicability to explaining the questions related to great power assertiveness in areas outside of their primary focus regions.

Keywords: Russia, Global South, great power, identity

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Authors: Ankita Jadon, Sidi Souvi, Nathalie Girault, Denis Petitprez

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Safety requirements for Generation IV nuclear reactor designs, especially the new generation sodium-cooled fast reactors (SFR) require a risk-informed approach to model severe accidents (SA) and their consequences in case of outside release. In SFRs, aerosols are produced during a core disruptive accident when primary system sodium is ejected into the containment and burn in contact with the air; producing sodium aerosols. One of the key aspects of safety evaluation is the in-containment sodium aerosol behavior and their interaction with fission products. The study of the effects of sodium fires is essential for safety evaluation as the fire can both thermally damage the containment vessel and cause an overpressurization risk. Besides, during the fire, airborne fission product first dissolved in the primary sodium can be aerosolized or, as it can be the case for fission products, released under the gaseous form. The objective of this work is to study the interactions between sodium aerosols and fission products (Iodine, toxic and volatile, being the primary concern). Sodium fires resulting from an SA would produce aerosols consisting of sodium peroxides, hydroxides, carbonates, and bicarbonates. In addition to being toxic (in oxide form), this aerosol will then become radioactive. If such aerosols are leaked into the environment, they can pose a danger to the ecosystem. Depending on the chemical affinity of these chemical forms with fission products, the radiological consequences of an SA leading to containment leak tightness loss will also be affected. This work is split into two phases. Firstly, a method to theoretically understand the kinetics and thermodynamics of the heterogeneous reaction between sodium aerosols and fission products: I2 and HI are proposed. Ab-initio, density functional theory (DFT) calculations using Vienna ab-initio simulation package are carried out to develop an understanding of the surfaces of sodium carbonate (Na2CO3) aerosols and hence provide insight on its affinity towards iodine species. A comprehensive study of I2 and HI adsorption, as well as bicarbonate formation on the calculated lowest energy surface of Na2CO3, was performed which provided adsorption energies and description of the optimized configuration of adsorbate on the stable surface. Secondly, the heterogeneous reaction between (I2)g and Na2CO3 aerosols were investigated experimentally. To study this, (I2)g was generated by heating a permeation tube containing solid I2, and, passing it through a reaction chamber containing Na2CO3 aerosol deposit. The concentration of iodine was then measured at the exit of the reaction chamber. Preliminary observations indicate that there is an effective uptake of (I2)g on Na2CO3 surface, as suggested by our theoretical chemistry calculations. This work is the first step in addressing the gaps in knowledge of in-containment and atmospheric source term which are essential aspects of safety evaluation of SFR SA. In particular, this study is aimed to determine and characterize the radiological and chemical source term. These results will then provide useful insights for the developments of new models to be implemented in integrated computer simulation tool to analyze and evaluate SFR safety designs.

Keywords: iodine adsorption, sodium aerosols, sodium cooled reactor, DFT calculations, sodium carbonate

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Authors: Momoka Sunohara, Ashley J. Lemieux, Esther Yakobov, Andrew G. Ryder, Tomas Jurcik

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Immigration brings changes in many aspects of an individual's life, from social support dynamics, to housing and language, as well as difficulties with regards to discrimination, trauma, and loss. Past research has mostly emphasized individual differences in mental health and has neglected the impact of social-ecological context, such as acculturation and ethnic density. Purpose: The present study aimed to assess the relationship between variables associated with social integration such as perceived ethnic density and ways of coping, as well as psychological adjustment in a rapidly growing non-visible minority group of immigrants in Canada. Data: A small subset of an archival data from our previously published study was reanalyzed with additional variables. Data included information from 269 Russian-Speaking immigrants in Montreal, Canada. Method: Canonical correlation analysis (CCA) investigated the relationship between two sets of variables. SAS PROC CANCORR was used to conduct CCA on a set of social integration variables, including ethnic density, discrimination, social support, family functioning, and acculturation, and a set of psychological well-being variables, including distress, depression, self-esteem, and life satisfaction. In addition, canonical redundancy analysis was performed to calculate the proportion of variances of original variables explained by their own canonical variates. Results: Significance tests using Rao’s F statistics indicated that the first two canonical correlations (i.e., r1 = 0.64, r2 = 0.40) were statistically significant (p-value < 0.0001). Additionally, canonical redundancy analysis showed that the first two well-being canonical variates explained separately 62.9% and 12.8% variances of the standardized well-being variables, whereas the first two social integration canonical variates explained separately 14.7% and 16.7% variances of the standardized social integration variables. These results support the selection of the first two canonical correlations. Then, we interpreted the derived canonical variates based on their canonical structure (i.e., correlations with original variables). Two observations can be concluded. First, individuals who have adequate social support, and who, as a family, cope by acquiring social support, mobilizing others and reframing are more likely to have better self-esteem, greater life satisfaction and experience less feelings of depression or distress. Second, individuals who feel discriminated yet rate higher on a mainstream acculturation scale, and who, as a family, cope by acquiring social support, mobilizing others and using spirituality, while using less passive strategies are more likely to have better life satisfaction but also higher degree of depression. Implications: This model may serve to explain the complex interactions that exist between social and emotional adjustment and aid in facilitating the integration of individuals immigrating into new communities. The same group may experience greater depression but paradoxically improved life satisfaction associated with their coping process. Such findings need to be placed in the context of Russian cultural values. For instance, some Russian-speakers may value the expression of negative emotions with significant others during the integration process; this in turn may make negative emotions more salient, but also facilitate a greater sense of family and community connection, as well as life satisfaction.

Keywords: acculturation, ethnic density, mental health, Russian-speaking

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Authors: Aurica P. Chiriac, Vera Balan, Mihai Asandulesa, Elena Butnaru, Nita Tudorachi, Elena Stoleru, Loredana E. Nita, Iordana Neamtu, Alina Diaconu, Liliana Mititelu-Tartau

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The interest for studying ‘smart’ materials is entirely justified and in this context were realized investigations on poly(2-hydroxyethylmethacrylate-co-3, 9-divinyl-2, 4, 8, 10-tetraoxaspiro (5.5) undecane), which is a macromolecular compound with sensibility at pH and temperature, gel formation capacity, binding properties, amphilicity, good oxidative and thermal stability. Physico-chemical characteristics in terms of the molecular weight, temperature-sensitive abilities and thermal stability, as well rheological, dielectric and spectroscopic properties were evaluated in correlation with further coupling capabilities. Differential scanning calorimetry investigation indicated Tg at 36.6 °C and a melting point at Tm=72.8°C, for the studied copolymer, and up to 200oC two exothermic processes (at 99.7°C and 148.8°C) were registered with losing weight of about 4 %, respective 19.27%, which indicate just processes of thermal decomposition (and not phenomena of thermal transition) owing to scission of the functional groups and breakage of the macromolecular chains. At the same time, the rheological studies (rotational tests) confirmed the non-Newtonian shear-thinning fluid behavior of the copolymer solution. The dielectric properties of the copolymer have been evaluated in order to investigate the relaxation processes and two relaxation processes under Tg value were registered and attributed to localized motions of polar groups from side chain macromolecules, or parts of them, without disturbing the main chains. According to literature and confirmed as well by our investigations, β-relaxation is assigned with the rotation of the ester side group and the γ-relaxation corresponds to the rotation of hydroxy- methyl side groups. The fluorescence spectroscopy confirmed the copolymer structure, the spiroacetal moiety getting an axial conformation, more stable, with lower energy, able for specific interactions with molecules from environment, phenomena underlined by different shapes of the emission spectra of the copolymer. Also, the copolymer was used as template for indomethacin incorporation as model drug, and the biocompatible character of the complex was confirmed. The release behavior of the bioactive compound was dependent by the copolymer matrix composition, the increasing of 3, 9-divinyl-2, 4, 8, 10-tetraoxaspiro (5.5) undecane comonomer amount attenuating the drug release. At the same time, the in vivo studies did not show significant differences of leucocyte formula elements, GOT, GPT and LDH levels, nor immune parameters (OC, PC, and BC) between control mice group and groups treated just with copolymer samples, with or without drug, data attesting the biocompatibility of the polymer samples. The investigation of the physico-chemical characteristics of poly(2-hydrxyethyl methacrylate-co-3, 9-divinyl-2, 4, 8, 10-tetraoxaspiro (5.5) undecane) in terms of temperature-sensitive abilities, rheological and dielectrical properties, are bringing useful information for further specific use of this polymeric compound.

Keywords: bioapplications, dielectric and spectroscopic properties, dual sensitivity at pH and temperature, smart materials

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Authors: Dagmara A. Niedziela, Mark P. Murphy, Orla M. Keane, Finola C. Leonard

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Staphylococcus aureus is the most frequent cause of clinical and subclinical bovine mastitis in Ireland. Mastitis caused by S. aureus is often chronic and tends to recur after antibiotic treatment. This may be due to several virulence factors, including attributes that enable the bacterium to internalize into bovine mammary epithelial cells, where it may evade antibiotic treatment, or evade the host immune response. Four bovine-adapted lineages (CC71, CC97, CC151 and ST136) were identified among a collection of Irish S. aureus mastitis isolates. Genotypic variation of mastitis-causing strains may contribute to different presentations of the disease, including differences in milk somatic cell count (SCC), the main method of mastitis detection. The objective of this study was to investigate the influence of bacterial strain and lineage on host immune response, by employing cell culture methods in vitro as well as an in vivo infection model. Twelve bovine adapted S. aureus strains were examined for internalization into bovine mammary epithelial cells (bMEC) and their ability to induce an immune response from bMEC (using qPCR and ELISA). In vitro studies found differences in a variety of virulence traits between the lineages. Strains from lineages CC97 and CC71 internalized more efficiently into bovine mammary epithelial cells (bMEC) than CC151 and ST136. CC97 strains also induced immune genes in bMEC more strongly than strains from the other 3 lineages. One strain each of CC151 and CC97 that differed in their ability to cause an immune response in bMEC were selected on the basis of the above in vitro experiments. Fourteen first-lactation Holstein-Friesian cows were purchased from 2 farms on the basis of low SCC (less than 50 000 cells/ml) and infection free status. Seven cows were infected with 1.73 x 102 c.f.u. of the CC97 strain (Group 1) and another seven with 5.83 x 102 c.f.u. of the CC151 strain (Group 2). The contralateral quarter of each cow was inoculated with PBS (vehicle). Clinical signs of infection (temperature, milk and udder appearance, milk yield) were monitored for 30 days. Blood and milk samples were taken to determine bacterial counts in milk, SCC, white blood cell populations and cytokines. Differences in disease presentation in vivo between groups were observed, with two animals from Group 2 developing clinical mastitis and requiring antibiotic treatment, while one animal from Group 1 did not develop an infection for the duration of the study. Fever (temperature > 39.5⁰C) was observed in 3 animals from Group 2 and in none from Group 1. Significant differences in SCC and bacterial load between groups were observed in the initial stages of infection (week 1). Data is also being collected on cytokines and chemokines secreted during the course of infection. The results of this study suggest that a strain from lineage CC151 may cause more severe clinical mastitis, while a strain from lineage CC97 may cause mild, subclinical mastitis. Diversity between strains of S. aureus may therefore influence the clinical presentation of mastitis, which in turn may influence disease detection and treatment needs.

Keywords: Bovine mastitis, host immune response, host-pathogen interactions, Staphylococcus aureus

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Authors: Haohua Zong, Marios Kotsonis

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Plasma synthetic jet actuator (PSJA) is a new concept of zero net mass flow actuator which utilizes pulsed arc/spark discharge to rapidly pressurize gas in a small cavity under constant-volume conditions. The unique combination of high exit jet velocity (>400 m/s) and high actuation frequency (>5 kHz) provides a promising solution for high-speed high-Reynolds-number flow control. This paper focuses on the performance of PSJA in repetitive working mode which is more relevant to future flow control applications. A two-electrodes PSJA (cavity volume: 424 mm3, orifice diameter: 2 mm) together with a capacitive discharge circuit (discharge energy: 50 mJ-110 mJ) is designed to enable repetitive operation. Time-Resolved Particle Imaging Velocimetry (TR-PIV) system working at 10 kHz is exploited to investigate the influence of discharge frequency on performance of PSJA. In total, seven cases are tested, covering a wide range of discharge frequencies (20 Hz-560 Hz). The pertinent flow features (shock wave, vortex ring and jet) remain the same for single shot mode and repetitive working mode. Shock wave is issued prior to jet eruption. Two distinct vortex rings are formed in one cycle. The first one is produced by the starting jet whereas the second one is related with the shock wave reflection in cavity. A sudden pressure rise is induced at the throat inlet by the reflection of primary shock wave, promoting the shedding of second vortex ring. In one cycle, jet exit velocity first increases sharply, then decreases almost linearly. Afterwards, an alternate occurrence of multiple jet stages and refresh stages is observed. By monitoring the dynamic evolution of exit velocity in one cycle, some integral performance parameters of PSJA can be deduced. As frequency increases, the jet intensity in steady phase decreases monotonically. In the investigated frequency range, jet duration time drops from 250 µs to 210 µs and peak jet velocity decreases from 53 m/s to approximately 39 m/s. The jet impulse and the expelled gas mass (0.69 µN∙s and 0.027 mg at 20 Hz) decline by 48% and 40%, respectively. However, the electro-mechanical efficiency of PSJA defined by the ratio of jet mechanical energy to capacitor energy doesn’t show significant difference (o(0.01%)). Fourier transformation of the temporal exit velocity signal indicates two dominant frequencies. One corresponds to the discharge frequency, while the other accounts for the alternation frequency of jet stage and refresh stage in one cycle. The alternation period (300 µs approximately) is independent of discharge frequency, and possibly determined intrinsically by the actuator geometry. A simple analytical model is established to interpret the alternation of jet stage and refresh stage. Results show that the dynamic response of exit velocity to a small-scale disturbance (jump in cavity pressure) can be treated as a second-order under-damping system. Oscillation frequency of the exit velocity, namely alternation frequency, is positively proportional to exit area, but inversely proportional to cavity volume and throat length. Theoretical value of alternation period (305 µs) agrees well with the experimental value.

Keywords: plasma, synthetic jet, actuator, frequency effect

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Authors: Adriana De Serio, Donato Forenza

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Aims. In this experimental research the Authors present the methodological plan “Musictherapy and Gardentherapy” that they created interconnected with the garden landscape ecosystems and aimed at PsychoPhysical Disability (MusGarPPhyD). In the context of the environmental education aimed at spreading the landscape culture and its values, it’s necessary to develop a solid perception of the environment sustainability to implement a multidimensional approach that pays attention to the conservation and enhancement of gardens and natural environments. The result is an improvement in the life quality also in compliance with the objectives of the European Agenda 2030. The MusGarPPhyD can help professionals such as musictherapists and environmental and landscape researchers strengthen subjects' motivation to learn to deal with the psychophysical discomfort associated with disability and to cope with the distress and the psychological fragility and the loneliness and the social seclusion and to promote productive social relationships. Materials and Methods. The MusGarPPhyD was implemented in multiple spaces. The musictherapy treatments took place first inside residential therapeutic centres and then in the garden landscape ecosystem. Patients: twenty, set in two groups. Weekly-sessions (50’) for three months. Methodological phases: - Phase P1. MusicTherapy treatments for each group in the indoor spaces. - Phase P2. MusicTherapy sessions inside the gardens. After each Phase, P1 and P2: - a Questionnaire for each patient (ten items / liking-indices) was administrated at t0 time, during the treatment and at tn time at the end of the treatment. - Monitoring of patients' behavioral responses through assessment scales, matrix, table and graph system. MusicTherapy methodology: pazient Sonorous-Musical Anamnesis, Musictherapy Assessment Document, Observation Protocols, Bodily-Environmental-Rhythmical-Sonorous-Vocal-Energy production first indoors and then outside, sonorous-musical instruments and edible instruments made by the Author/musictherapist with some foods; Administration of Patient-Environment-Music Index at time to and tn, to estimate the patient’s behavior evolution, Musictherapeutic Advancement Index. Results. The MusGarPPhyD can strengthen the individual sense of identity and improve the psychophysical skills and the resilience to face and to overcome the difficulties caused by the congenital /acquired disability. The multi-sensory perceptions deriving from contact with the plants in the gardens improve the psychological well-being and regulate the physiological parameters such as blood pressure, cardiac and respiratory rhythm, reducing the cholesterol levels. The secretions of the peptide hormones endorphins and the endogenous opioids enkephalins increase and bring a state of patient’s tranquillity and a better mood. The subjects showed a preference for musictherapy treatments within a setting made up of gardens and peculiar landscape systems. This resulted in greater health benefits. Conclusions. The MusGarPPhyD contributes to reduce psychophysical tensions, anxiety, depression and stress, facilitating the connections between the cerebral hemispheres, thus also improving intellectual performances, self-confidence, motor skills and social interactions. Therefore it is necessary to design hospitals, rehabilitation centers, nursing homes, surrounded by gardens. Ecosystems of natural and urban parks and gardens create fascinating skyline and mosaics of landscapes rich in beauty and biodiversity. The MusGarPPhyD is useful for the health management promoting patient’s psychophysical activation, better mood/affective-tone and relastionships and contributing significantly to improving the life quality.

Keywords: musictherapy, gardentherapy, disability, life quality

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Authors: Antonela Matana, Dubravka Brdar, Vesela Torlak, Marijana Popovic, Ivana Gunjaca, Ozren Polasek, Vesna Boraska Perica, Maja Barbalic, Ante Punda, Caroline Hayward, Tatijana Zemunik

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Parathyroid hormone (PTH) plays a critical role in the regulation of bone mineral metabolism and calcium homeostasis. Higher PTH levels are associated with heart failure, hypertension, coronary artery disease, cardiovascular mortality and poorer bone health. A twin study estimated that 60% of the variation in PTH concentrations is genetically determined. Only one GWAS of PTH concentration has been reported to date. Identified loci explained 4.5% of the variance in circulating PTH, suggesting that additional genetic variants remain undiscovered. Therefore, the aim of this study was to identify novel genetic variants associated with PTH levels in a general population. We have performed a GWAS meta-analysis on 2596 individuals originating from three Croatian cohorts: City of Split and the Islands of Korčula and Vis, within a large-scale project of “10,001 Dalmatians”. A total of 7 411 206 variants, imputed using the 1000 Genomes reference panel, with minor allele frequency ≥ 1% and Rsq ≥ 0.5 were analyzed for the association. GWAS within each data set was performed under an additive model, controlling for age, gender and relatedness. Meta-analysis was conducted using the inverse-variance fixed-effects method. Furthermore, to identify sex-specific effects, we have conducted GWAS meta-analyses analyzing males and females separately. In addition, we have performed biological pathway analysis. Four SNPs, representing one locus, reached genome-wide significance. The most significant SNP was rs11099476 on chromosome 4 (P=1.15x10-8), which explained 1.14 % of the variance in PTH. The SNP is located near the protein-coding gene RASGEF1B. Additionally, we detected suggestive association with SNPs, rs77178854 located on chromosome 2 in the DPP10 gene (P=2.46x10-7) and rs481121 located on chromosome 1 (P=3.58x10-7) near the GRIK1 gene. One of the top hits detected in the main meta-analysis, intron variant rs77178854 located within DPP10 gene, reached genome-wide significance in females (P=2.21x10-9). No single locus was identified in the meta-analysis in males. Fifteen biological pathways were functionally enriched at a P<0.01, including muscle contraction, ion homeostasis and cardiac conduction as the most significant pathways. RASGEF1B is the guanine nucleotide exchange factor, known to be associated with height, bone density, and hip. DPP10 encodes a membrane protein that is a member of the serine proteases family, which binds specific voltage-gated potassium channels and alters their expression and biophysical properties. In conclusion, we identified 2 novel loci associated with PTH levels in a general population, providing us with further insights into the genetics of this complex trait.

Keywords: general population, genome-wide association analysis, parathyroid hormone, single nucleotide polymorphisms.

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Authors: Amr Mansour, Boaz Granot, Amani Tatar, Assil Mahamid, Mohammad Haj Yahia, Fairoz Jayyusi, Eyal Behrbalk

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INTRODUCTION: Distal radius fractures are common orthopedic injuries often treated in the fast-paced, high-stress environment of emergency departments (EDs). In such settings, patient satisfaction can be significantly influenced by the clarity of communication and the accessibility of information This study explores the impact of providing an informational pamphlet that outlines ED processes, treatment expectations, and follow-up instructions on patient satisfaction across key domains, including trust, communication, organization, responsiveness, and overall experience. We hypothesize that a structured informational pamphlet will enhance patient satisfaction by fostering better understanding and aligning patient expectations with the realities of the ED visit. METHODS: A total of 100 adult patients treated for distal radius fractures between January and August 2024 participated in this survey-based study. Patients were randomized into two equal groups: one group received an informational pamphlet detailing their condition and treatment, while the other did not. Satisfaction levels were assessed using a structured questionnaire addressing five domains. Fisher's exact test was used to compare satisfaction measures between the two groups, and multivariate logistic regression analysis was conducted to evaluate the association between receiving an information sheet and high satisfaction. The study was approved by the Institutional Review Board. RESULTS SECTION: Patients who received an informational pamphlet reported significantly higher satisfaction across all five domains (p < .001). In Trust and Understanding, 82% of info-sheet recipients felt “in good hands,” compared to 10% of non-recipients. For Communication, 86% rated doctor explanations as “very clear,” versus 16% among non-recipients. Logistic regression showed that receiving an informational pamphlet was a significant predictor of high satisfaction with Discharge Explanation—clarity on condition, treatment, and follow-up (OR = 17.65, 95% CI: 4.74 - 65.77, p < .001) and Reasonable Solution—feeling their primary concern was resolved (OR = 37.82, 95% CI: 8.75 - 163.42, p < .001). Other predictors, including fracture reduction, gender, and age, were not significant. DISCUSSION: This study highlights the substantial role that simple, cost-effective interventions like informational pamphlets can play in enhancing patient satisfaction in emergency care. By improving communication, fostering trust, and promoting a patient-centered approach, informational pamphlets offer a valuable tool for healthcare providers seeking to enhance the quality of care and patient experience in high-pressure emergency environments. However, the study's limitations, including its single-center design and reliance on self-reported satisfaction scores, may affect the generalizability of the results. Future research should consider a multi-center approach and explore long-term outcomes to further validate the efficacy of informational pamphlets in diverse ED settings. Ultimately, sustained improvement in patient satisfaction is a complex and dynamic issue necessitating a multifactorial approach, and other methods should also be explored to complement this strategy. SIGNIFICANCE/CLINICAL RELEVANCE: This study demonstrates that providing an informational pamphlet in the ED setting can significantly improve patient satisfaction across multiple domains, emphasizing its potential as a simple, cost-effective tool to enhance communication, trust, and overall patient experience during emergency care for distal radius fractures. Integrating such interventions into standard ED protocols may foster a more patient-centered approach, improving both patient outcomes and healthcare efficiency.

Keywords: distal radius fracture, quality care, patient satisfaction, emergency medicine, patient-centered care, communication

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Authors: Reggie Chandra

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Trafficaccidents and traffic signal optimization are correlated. However, 70-90% of the traffic signals across the USA are not synchronized. The reason behind that is insufficient resources to create and implement timing plans. In this work, we will discuss the use of a breakthrough Artificial Intelligence (AI) technology to optimize traffic flow and collect 24/7/365 accurate traffic data using a vehicle detection system. We will discuss what are recent advances in Artificial Intelligence technology, how does AI work in vehicles, pedestrians, and bike data collection, creating timing plans, and what is the best workflow for that. Apart from that, this paper will showcase how Artificial Intelligence makes signal timing affordable. We will introduce a technology that uses Convolutional Neural Networks (CNN) and deep learning algorithms to detect, collect data, develop timing plans and deploy them in the field. Convolutional Neural Networks are a class of deep learning networks inspired by the biological processes in the visual cortex. A neural net is modeled after the human brain. It consists of millions of densely connected processing nodes. It is a form of machine learning where the neural net learns to recognize vehicles through training - which is called Deep Learning. The well-trained algorithm overcomes most of the issues faced by other detection methods and provides nearly 100% traffic data accuracy. Through this continuous learning-based method, we can constantly update traffic patterns, generate an unlimited number of timing plans and thus improve vehicle flow. Convolutional Neural Networks not only outperform other detection algorithms but also, in cases such as classifying objects into fine-grained categories, outperform humans. Safety is of primary importance to traffic professionals, but they don't have the studies or data to support their decisions. Currently, one-third of transportation agencies do not collect pedestrian and bike data. We will discuss how the use of Artificial Intelligence for data collection can help reduce pedestrian fatalities and enhance the safety of all vulnerable road users. Moreover, it provides traffic engineers with tools that allow them to unleash their potential, instead of dealing with constant complaints, a snapshot of limited handpicked data, dealing with multiple systems requiring additional work for adaptation. The methodologies used and proposed in the research contain a camera model identification method based on deep Convolutional Neural Networks. The proposed application was evaluated on our data sets acquired through a variety of daily real-world road conditions and compared with the performance of the commonly used methods requiring data collection by counting, evaluating, and adapting it, and running it through well-established algorithms, and then deploying it to the field. This work explores themes such as how technologies powered by Artificial Intelligence can benefit your community and how to translate the complex and often overwhelming benefits into a language accessible to elected officials, community leaders, and the public. Exploring such topics empowers citizens with insider knowledge about the potential of better traffic technology to save lives and improve communities. The synergies that Artificial Intelligence brings to traffic signal control and data collection are unsurpassed.

Keywords: artificial intelligence, convolutional neural networks, data collection, signal control, traffic signal

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Authors: Isabelle Barrett

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Natural watercourses provide a range of vital ecosystem services, notably freshwater provision. They also offer highly heterogeneous habitat which supports an extreme diversity of aquatic life. Exploitation of rivers, changing land use and flood prevention measures have led to habitat degradation and subsequent biodiversity loss; indeed, freshwater species currently face a disproportionate rate of extinction compared to their terrestrial and marine counterparts. Large woody debris (LWD) encompasses the trees, large branches and logs which fall into watercourses, and is responsible for important habitat characteristics. Historically, natural LWD has been removed from streams under the assumption that it is not aesthetically pleasing and is thus ecologically unfavourable, despite extensive evidence contradicting this. Restoration efforts aim to replace lost LWD in order to reinstate habitat heterogeneity. This paper aims to assess the current state of such restoration schemes for improving fluvial ecological health in the UK. A detailed review of the scientific literature was conducted alongside a meta-analysis of 25 UK-based projects involving LWD restoration. Projects were chosen for which sufficient information was attainable for analysis, covering a broad range of budgets and scales. The most effective strategies for river restoration encompass ecological success, stakeholder engagement and scientific advancement, however few projects surveyed showed sensitivity to all three; for example, only 32% of projects stated biological aims. Focus tended to be on stakeholder engagement and public approval, since this is often a key funding driver. Consequently, there is a tendency to focus on the aesthetic outcomes of a project, however physical habitat restoration does not necessarily lead to direct biodiversity increases. This highlights the significance of rivers as highly heterogeneous environments with multiple interlinked processes, and emphasises a need for a stronger scientific presence in project planning. Poor scientific rigour means monitoring is often lacking, with varying, if any, definitions of success which are rarely pre-determined. A tendency to overlook negative or neutral results was apparent, with unjustified focus often put on qualitative results. The temporal scale of monitoring is typically inadequate to facilitate scientific conclusions, with only 20% of projects surveyed reporting any pre-restoration monitoring. Furthermore, monitoring is often limited to a few variables, with biotic monitoring often fish-focussed. Due to their longer life cycles and dispersal capability, fish are usually poor indicators of environmental change, making it difficult to attribute any changes in ecological health to restoration efforts. Although the potential impact of LWD restoration may be positive, this method of restoration could simply be making short-term, small-scale improvements; without addressing the underlying symptoms of degradation, for example water quality, the issue cannot be fully resolved. Promotion of standardised monitoring for LWD projects could help establish a deeper understanding of the ecology surrounding the practice, supporting movement towards adaptive management in which scientific evidence feeds back to practitioners, enabling the design of more efficient projects with greater ecological success. By highlighting LWD, this study hopes to address the difficulties faced within river management, and emphasise the need for a more holistic international and inter-institutional approach to tackling problems associated with degradation.

Keywords: biological monitoring, ecological health, large woody debris, river management, river restoration

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Authors: Yi Li, Rui Lu, Lianjun Wang

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With the rapid development of chemical industry, the consumption of volatile organic compounds (VOCs) has increased extensively. In the process of VOCs production and application, plenty of them have been transferred to environment. As a result, it has led to pollution problems not only in soil and ground water but also to human beings. Thus, it is important to develop a sensitive and cost-effective analytical method for trace VOCs detection in environment. Surface-enhanced Raman Spectroscopy (SERS), as one of the most sensitive optical analytical technique with rapid response, pinpoint accuracy and noninvasive detection, has been widely used for ultratrace analysis. Based on the plasmon resonance on the nanoscale metallic surface, SERS technology can even detect single molecule due to abundant nanogaps (i.e. 'hot spots') on the nanosubstrate. In this work, a self-supported flexible silver nitrate (AgNO3)/ethylene-propylene copolymer (EPM) hybrid nanofibers was fabricated by electrospinning. After an in-situ chemical reduction using ice-cold sodium borohydride as reduction agent, numerous silver nanoparticles were formed on the nanofiber surface. By adjusting the reduction time and AgNO3 content, the morphology and dimension of silver nanoparticles could be controlled. According to the principles of solid-phase extraction, the hydrophobic substance is more likely to partition into the hydrophobic EPM membrane in an aqueous environment while water and other polar components are excluded from the analytes. By the enrichment of EPM fibers, the number of hydrophobic molecules located on the 'hot spots' generated from criss-crossed nanofibers is greatly increased, which further enhances SERS signal intensity. The as-prepared Ag/EPM hybrid nanofibers were first employed to detect common SERS probe molecule (p-aminothiophenol) with the detection limit down to 10-12 M, which demonstrated an excellent SERS performance. To further study the application of the fabricated substrate for monitoring hydrophobic substance in water, several typical VOCs, such as benzene, toluene and p-xylene, were selected as model compounds. The results showed that the characteristic peaks of these target analytes in the mixed aqueous solution could be distinguished even at a concentration of 10-6 M after multi-peaks gaussian fitting process, including C-H bending (850 cm-1), C-C ring stretching (1581 cm-1, 1600 cm-1) of benzene, C-H bending (844 cm-1 ,1151 cm-1), C-C ring stretching (1001 cm-1), CH3 bending vibration (1377 cm-1) of toluene, C-H bending (829 cm-1), C-C stretching (1614 cm-1) of p-xylene. The SERS substrate has remarkable advantages which combine the enrichment capacity from EPM and the Raman enhancement of Ag nanoparticles. Meanwhile, the huge specific surface area resulted from electrospinning is benificial to increase the number of adsoption sites and promotes 'hot spots' formation. In summary, this work provides powerful potential in rapid, on-site and accurate detection of trace VOCs using a portable Raman.

Keywords: electrospinning, ethylene-propylene copolymer, silver nanoparticles, SERS, VOCs

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Authors: N. Rambabu, H. Gururaj, Reynold Washington, Oommen George

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Motivation: Under the USAID Strengthening Health Outcomes through Private Sector (SHOPS-TB) initiative, Karnataka Health Promotion Trust (KHPT) with technical support of Abt associates is implementing a TB prevention and care model in Karnataka State, South India. KHPT is the interface agency between the public and private sectors, and providers and the target community facilitating early TB case detection and enhancing treatment compliance through private health care providers (pHCP) engagement in RNTCP. The project coverage is 0.84 million urban poor from 663 slums in 12 districts of Karnataka. Problem Statement: India with the highest burden of global TB (26%) and two million cases annually, accounts for approximately one fifth of the global incidence. WHO estimates 300,000 people die from TB annually in India. India expanded the coverage of Directly Observed Treatment, Short-course chemotherapy (DOTS) to the entire country as early as 2006. However, the performance of RNTCP has not been uniform across states. While the national annual new smear-positive (NSP) case notification rate is 53, it is much lower at 47 in Karnataka. A third of TB patients in India reside in urban slums. Approach: Under SHOPS, KHPT actively engages with communities through key opinion leaders and community structures. Interpersonal communication, by Outreach workers through house-to-house visits and at aggregation points, is the primary method used for communication about TB and its management and to increase demand for sputum examination and DOTS. pHCP are mapped, trained and mentored by KHPT. ORWs also provide patient and family counseling on TB treatment, side effects and adherence, screen close contacts of index patients especially children under 6 years of age and screen co-morbidities including HIV, diabetes and malnutrition and risk factors including alcoholism, tobacco use, occupational hazards making appropriate accompanied or documented referrals. A treatment ‘buddy’ system for the patients involving close friends or family members, ICT-based support, DOTS Prerana (inspiration) groups of TB patients, family members and community, DOTS Mitra (friend) helpline services are also used for care and support services. Results: The intervention educated 39988 slum dwellers, referred 1731 chest symptomatics, tested 1061 patients and initiated 248 patients on anti-TB treatment within three months of intervention through continuous community engagement. Conclusions: The intervention’s potential to increase access to preferred health care providers, reduce patient and health system delays in diagnosis and initiation of treatment, improve health seeking behaviour and enhance compliance of pHCPs to standard treatment protocols is being monitored. Initial results are promising.

Keywords: DOTS, KHPT, health outcomes, public and private sector

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Authors: Ewelina Wisnik, Zsolt Regdon, Kinga Chmielewska, Laszlo Virag, Agnieszka Robaszkiewicz

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Apart from protecting genome, PARP1 has been documented to regulate many intracellular processes inter alia gene transcription by physically interacting with chromatin bound proteins and by their ADP-ribosylation. Our recent findings indicate that expression of PARP1 decreases during the differentiation of human CD34+ hematopoietic stem cells to monocytes as a consequence of differentiation-associated cell growth arrest and formation of E2F4-RBL2-HDAC1-SWI/SNF repressive complex at the promoter of this gene. Since the RBL2 complexes repress genes in a E2F-dependent manner and are widespread in the genome in G0 arrested cells, we asked (a) if RBL2 directly contributes to defining monocyte phenotype and function by targeting gene promoters and (b) if RBL2 controls gene transcription indirectly by repressing PARP1. For identification of genes controlled by RBL2 and/or PARP1,we used primer libraries for surface receptors and TLR signaling mediators, genes were silenced by siRNA or shRNA, analysis of gene promoter occupation by selected proteins was carried out by ChIP-qPCR, while statistical analysis in GraphPad Prism 5 and STATISTICA, ChIP-Seq data were analysed in Galaxy 2.5.0.0. On the list of 28 genes regulated by RBL2, we identified only four solely repressed by RBL2-E2F4-HDAC1-BRM complex. Surprisingly, 24 out of 28 emerged genes controlled by RBL2 were co-regulated by PARP1 in six different manners. In one mode of RBL2/PARP1 co-operation, represented by MAP2K6 and MAPK3, PARP1 was found to associate with gene promoters upon RBL2 silencing, which was previously shown to restore PARP1 expression in monocytes. PARP1 effect on gene transcription was observed only in the presence of active EP300, which acetylated gene promoters and activated transcription. Further analysis revealed that PARP1 binding to MA2K6 and MAPK3 promoters enabled recruitment of EP300 in monocytes, while in proliferating cancer cell lines, which actively transcribe PARP1, this protein maintained EP300 at the promoters of MA2K6 and MAPK3. Genome-wide analysis revealed a similar distribution of PARP1 and EP300 around transcription start sites and the co-occupancy of some gene promoters by PARP1 and EP300 in cancer cells. Here, we described a new RBL2/PARP1/EP300 axis which controls gene transcription regardless of the cell type. In this model cell, cycle-dependent transcription of PARP1 regulates expression of some genes repressed by RBL2 upon cell cycle limitation. Thus, RBL2 may indirectly regulate transcription of some genes by controlling the expression of EP300-recruiting PARP1. Acknowledgement: This work was financed by Polish National Science Centre grants nr DEC-2013/11/D/NZ2/00033 and DEC-2015/19/N/NZ2/01735. L.V. is funded by the National Research, Development and Innovation Office grants GINOP-2.3.2-15-2016-00020 TUMORDNS, GINOP-2.3.2-15-2016-00048-STAYALIVE and OTKA K112336. AR is supported by Polish Ministry of Science and Higher Education 776/STYP/11/2016.

Keywords: retinoblastoma transcriptional co-repressor like 2 (RBL2), poly(ADP-ribose) polymerase 1 (PARP1), E1A binding protein p300 (EP300), monocytes

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Authors: Matthias Haenisch, Marc Godau, Julia Barreiro, Dominik Maxelon

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In times of ubiquitous digitalization and the increasing entanglement of humans and technologies in musical practices in the 21st century, it is to be asked, how popular musicians learn in the (post)digital Age. Against the backdrop of the increasing interest in transferring informal learning practices into formal settings of music education the interdisciplinary research association »MusCoDA – Musical Communities in the (Post)Digital Age« (University of Erfurt/University of Applied Sciences Clara Hoffbauer Potsdam, funded by the German Ministry of Education and Research, pursues the goal to derive an empirical model of collective songwriting practices from the study of informal lelearningf songwriters and bands that can be translated into pedagogical concepts for music education in schools. Drawing on concepts from Community of Musical Practice and Actor Network Theory, lelearnings considered not only as social practice and as participation in online and offline communities, but also as an effect of heterogeneous networks composed of human and non-human actors. Learning is not seen as an individual, cognitive process, but as the formation and transformation of actor networks, i.e., as a practice of assembling and mediating humans and technologies. Based on video stimulated recall interviews and videography of online and offline activities, songwriting practices are followed from the initial idea to different forms of performance and distribution. The data evaluation combines coding and mapping methods of Grounded Theory Methodology and Situational Analysis. This results in network maps in which both the temporality of creative practices and the material and spatial relations of human and technological actors are reconstructed. In addition, positional analyses document the power relations between the participants that structure the learning process of the field. In the area of online informal lelearninginitial key research findings reveal a transformation of the learning subject through the specific technological affordances of TikTok and Instagram and the accompanying changes in the learning practices of the corresponding online communities. Learning is explicitly shaped by the material agency of online tools and features and the social practices entangled with these technologies. Thus, any human online community member can be invited to directly intervene in creative decisions that contribute to the further compositional and structural development of songs. At the same time, participants can provide each other with intimate insights into songwriting processes in progress and have the opportunity to perform together with strangers and idols. Online Lelearnings characterized by an increase in social proximity, distribution of creative agency and informational exchange between participants. While it seems obvious that traditional notions not only of lelearningut also of the learning subject cannot be maintained, the question arises, how exactly the observed informal learning practices and the subject that emerges from the use of social media as online learning technologies can be transferred into contexts of formal learning

Keywords: informal learning, postdigitality, songwriting, actor-network theory, community of musical practice, social media, TikTok, Instagram, apps

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Authors: Stéphanie Looser, Walter Wehrmeyer

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Given the limited research on Small and Mediumsized Enterprises’ (SMEs) contribution to Corporate Social Responsibility (CSR) and even scarcer research on Swiss SMEs, this paper helps to fill these gaps by enabling the identification of supranational SME parameters and to make a contribution to the evolving field of these topics. Thus, the paper investigates the current state of SME practices in Switzerland and across 15 other countries. Combining the degree to which SMEs demonstrate an explicit (or business case) approach or see CSR as an implicit moral activity with the assessment of their attributes for “variety of capitalism” defines the framework of this comparative analysis. According to previous studies, liberal market economies, e.g. in the United States (US) or United Kingdom (UK), are aligned with extrinsic CSR, while coordinated market systems (in Central European or Asian countries) evolve implicit CSR agendas. To outline Swiss small business CSR patterns in particular, 40 SME owner-managers were interviewed. The transcribed interviews were coded utilising MAXQDA for qualitative content analysis. A secondary data analysis of results from different countries (i.e., Australia, Austria, Chile, Cameroon, Catalonia (notably a part of Spain that seeks autonomy), China, Finland, Germany, Hong Kong (a special administrative region of China), Italy, Netherlands, Singapore, Spain, Taiwan, UK, US) lays groundwork for this comparative study on small business CSR. Applying the same coding categories (in MAXQDA) for the interview analysis as well as for the secondary data research while following grounded theory rules to refine and keep track of ideas generated testable hypotheses and comparative power on implicit (and the lower likelihood of explicit) CSR in SMEs retrospectively. The paper identifies Swiss small business CSR as deep, profound, “soul”, and an implicit part of the day-to-day business. Similar to most Central European, Mediterranean, Nordic, and Asian countries, explicit CSR is still very rare in Swiss SMEs. Astonishingly, also UK and US SMEs follow this pattern in spite of their strong and distinct liberal market economies. Though other findings show that nationality matters this research concludes that SME culture and its informal CSR agenda are strongly formative and superseding even forces of market economies, nationally cultural patterns, and language. In a world of “big business”, explicit “business case” CSR, and the mantra that “CSR must pay”, this study points to a distinctly implicit small business CSR model built on trust, physical closeness, and virtues that is largely detached from the bottom line. This pattern holds for different cultural contexts and it is concluded that SME culture is stronger than nationality leading to a supra-national, monolithic SME CSR approach. Hence, classifications of countries by their market system or capitalism, as found in the comparative capitalism literature, do not match the CSR practices in SMEs as they do not mirror the peculiarities of their business. This raises questions on the universality and generalisability of management concepts.

Keywords: CSR, comparative study, cultures of capitalism, small, medium-sized enterprises

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Authors: Trevor C. Brown, David J. Miron

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Gas-solid physical adsorption methods are central to the characterization and optimization of the effective surface area, pore size and porosity for applications such as heterogeneous catalysis, and gas separation and storage. Properties such as adsorption uptake, capacity, equilibrium constants and Gibbs free energy are dependent on the composition and structure of both the gas and the adsorbent. However, challenges remain, in accurately calculating these properties from experimental data. Gas adsorption experiments involve measuring the amounts of gas adsorbed over a range of pressures under isothermal conditions. Various constant-parameter models, such as Langmuir and Brunauer-Emmett-Teller (BET) theories are used to provide information on adsorbate and adsorbent properties from the isotherm data. These models typically do not provide accurate interpretations across the full range of pressures and temperatures. The Langmuir adsorption isotherm is a simple approximation for modelling equilibrium adsorption data and has been effective in estimating surface areas and catalytic rate laws, particularly for high surface area solids. The Langmuir isotherm assumes the systematic filling of identical adsorption sites to a monolayer coverage. The BET model is based on the Langmuir isotherm and allows for the formation of multiple layers. These additional layers do not interact with the first layer and the energetics are equal to the adsorbate as a bulk liquid. This BET method is widely used to measure the specific surface area of materials. Both Langmuir and BET models assume that the affinity of the gas for all adsorption sites are identical and so the calculated adsorbent uptake at the monolayer and equilibrium constant are independent of coverage and pressure. Accurate representations of adsorption data have been achieved by extending the Langmuir and BET models to include pressure-varying uptake capacities and equilibrium constants. These parameters are determined using a novel regression technique called flexible least squares for time-varying linear regression. For isothermal adsorption the adsorption parameters are assumed to vary slowly and smoothly with increasing pressure. The flexible least squares for pressure-varying linear regression (FLS-PVLR) approach assumes two distinct types of discrepancy terms, dynamic and measurement for all parameters in the linear equation used to simulate the data. Dynamic terms account for pressure variation in successive parameter vectors, and measurement terms account for differences between observed and theoretically predicted outcomes via linear regression. The resultant pressure-varying parameters are optimized by minimizing both dynamic and measurement residual squared errors. Validation of this methodology has been achieved by simulating adsorption data for n-butane and isobutane on activated carbon at 298 K, 323 K and 348 K and for nitrogen on mesoporous alumina at 77 K with pressure-varying Langmuir and BET adsorption parameters (equilibrium constants and uptake capacities). This modeling provides information on the adsorbent (accessible surface area and micropore volume), adsorbate (molecular areas and volumes) and thermodynamic (Gibbs free energies) variations of the adsorption sites.

Keywords: Langmuir adsorption isotherm, BET adsorption isotherm, pressure-varying adsorption parameters, adsorbate and adsorbent properties and energetics

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Authors: Jenson George, Thoa Nguyen, Garth Sanewski, Craig Hardner, Heather Eunice Smyth

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Pineapple (Ananas comosus), with its unique sweet flavour, is one of the most popular tropical, non-climacteric fruits consumed worldwide. It is also the third most important tropical fruit in world production. In Australia, 99% of the pineapple production is from the Queensland state due to the favourable subtropical climatic conditions. The flavourful fruit is known to contain around 500 volatile organic compounds (VOC) at varying concentrations and greatly contribute to the flavour quality of pineapple fruit by providing distinct aroma sensory properties that are sweet, fruity, tropical, pineapple-like, caramel-like, coconut-like, etc. The aroma of pineapple is one of the important factors attracting consumers and strengthening the marketplace. To better understand the aroma of Australian-grown pineapples, the matrix-matched Gas chromatography–mass spectrometry (GC-MS), Head Space - Solid-phase microextraction (HS-SPME), Stable-isotope dilution analysis (SIDA) method was developed and validated. The developed method represents a significant improvement over current methods with the incorporation of multiple external reference standards, multiple isotopes labeled internal standards, and a matching model system of pineapple fruit matrix. This method was employed to quantify 28 key aroma compounds in more than 200 genetically diverse pineapple varieties from a breeding program. The Australian pineapple cultivars varied in content and composition of free volatile compounds, which were predominantly comprised of esters, followed by terpenes, alcohols, aldehydes, and ketones. Using selected commercial cultivars grown in Australia, and by employing the sensorial analysis, the appearance (colour), aroma (intensity, sweet, vinegar/tang, tropical fruits, floral, coconut, green, metallic, vegetal, fresh, peppery, fermented, eggy/sulphurous) and texture (crunchiness, fibrousness, and juiciness) were obtained. Relationships between sensory descriptors and volatiles were explored by applying multivariate analysis (PCA) to the sensorial and chemical data. The key aroma compounds of pineapple exhibited a positive correlation with corresponding sensory properties. The sensory and volatile data were also used to explore genetic diversity in the breeding population. GWAS was employed to unravel the genetic control of the pineapple volatilome and its interplay with fruit sensory characteristics. This study enhances our understanding of pineapple aroma (flavour) compounds, their biosynthetic pathways and expands breeding option for pineapple cultivars. This research provides foundational knowledge to support breeding programs, post-harvest and target market studies, and efforts to optimise the flavour of commercial pineapple varieties and their parent lines to produce better tasting fruits for consumers.

Keywords: Ananas comosus, pineapple, flavour, volatile organic compounds, aroma, Gas chromatography–mass spectrometry (GC-MS), Head Space - Solid-phase microextraction (HS-SPME), Stable-isotope dilution analysis (SIDA).

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Authors: Nur A. Özdemir, Sude Erkin, Hatice K. Güney, Cemre S. Atılgan, Enes Huylu, Hüseyin Y. Altıntaş, Aysemin Top, Özak Durmuş

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Carbon emissions produced during a product’s life cycle, from extraction of raw materials up to waste disposal and market consumption activities are the major contributors to global warming. In the light of the science-based targets (SBT) leading the way to a zero-carbon economy for sustainable growth of the companies, carbon footprint reporting of the purchased goods has become critical for identifying hotspots and best practices for emission reduction opportunities. In line with Ford Otosan's corporate sustainability strategy, research was conducted to evaluate the carbon footprint of purchased products in accordance with Scope 3 of the Greenhouse Gas Protocol (GHG). The purpose of this paper is to develop a systematic and transparent methodology to calculate carbon footprint of the products produced by automotive OEMs (Original Equipment Manufacturers) within the context of automobile supply chain management. To begin with, primary material data were collected through IMDS (International Material Database System) corresponds to company’s three distinct types of vehicles including Light Commercial Vehicle (Courier), Medium Commercial Vehicle (Transit and Transit Custom), Heavy Commercial Vehicle (F-MAX). Obtained material data was classified as metals, plastics, liquids, electronics, and others to get insights about the overall material distribution of produced vehicles and matched to the SimaPro Ecoinvent 3 database which is one of the most extent versions for modelling material data related to the product life cycle. Product life cycle analysis was calculated within the framework of ISO 14040 – 14044 standards by addressing the requirements and procedures. A comprehensive literature review and cooperation with suppliers were undertaken to identify the production methods of parts used in vehicles and to find out the amount of scrap generated during part production. Cumulative weight and material information with related production process belonging the components were listed by multiplying with current sales figures. The results of the study show a key modelling on carbon footprint of products and processes based on a scientific approach to drive sustainable growth by setting straightforward, science-based emission reduction targets. Hence, this study targets to identify the hotspots and correspondingly provide broad ideas about our understanding of how to integrate carbon footprint estimates into our company's supply chain management by defining convenient actions in line with climate science. According to emission values arising from the production phase including raw material extraction and material processing for Ford OTOSAN vehicles subjected in this study, GHG emissions from the production of metals used for HCV, MCV and LCV account for more than half of the carbon footprint of the vehicle's production. Correspondingly, aluminum and steel have the largest share among all material types and achieving carbon neutrality in the steel and aluminum industry is of great significance to the world, which will also present an immense impact on the automobile industry. Strategic product sustainability plan which includes the use of secondary materials, conversion to green energy and low-energy process design is required to reduce emissions of steel, aluminum, and plastics due to the projected increase in total volume by 2030.

Keywords: automotive, carbon footprint, IMDS, scope 3, SimaPro, sustainability

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Authors: Dominique Arrouays, Songchao Chen, Anne C. Richer-De-Forges

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Soils are at the crossing of many issues such as food and water security, sustainable energy, climate change mitigation and adaptation, biodiversity protection, human health and well-being. They deliver many ecosystem services that are essential to life on Earth. Therefore, there is a growing demand for soil information on a national and global scale. Unfortunately, many countries do not have detailed soil maps, and, when existing, these maps are generally based on more or less complex and often non-harmonized soil classifications. An estimate of their uncertainty is also often missing. Thus, there are not easy to understand and often not properly used by end-users. Therefore, there is an urgent need to provide end-users with spatially exhaustive grids of essential soil properties, together with an estimate of their uncertainty. One way to achieve this is digital soil mapping (DSM). The concept of DSM relies on the hypothesis that soils and their properties are not randomly distributed, but that they depend on the main soil-forming factors that are climate, organisms, relief, parent material, time (age), and position in space. All these forming factors can be approximated using several exhaustive spatial products such as climatic grids, remote sensing products or vegetation maps, digital elevation models, geological or lithological maps, spatial coordinates of soil information, etc. Thus, DSM generally relies on models calibrated with existing observed soil data (point observations or maps) and so-called “ancillary co-variates” that come from other available spatial products. Then the model is generalized on grids where soil parameters are unknown in order to predict them, and the prediction performances are validated using various methods. With the growing demand for soil information at a national and global scale and the increase of available spatial co-variates national and continental DSM initiatives are continuously increasing. This short review illustrates the main national and continental advances in Europe, the diversity of the approaches and the databases that are used, the validation techniques and the main scientific and other issues. Examples from several countries illustrate the variety of products that were delivered during the last ten years. The scientific production on this topic is continuously increasing and new models and approaches are developed at an incredible speed. Most of the digital soil mapping (DSM) products rely mainly on machine learning (ML) prediction models and/or the use or pedotransfer functions (PTF) in which calibration data come from soil analyses performed in labs or for existing conventional maps. However, some scientific issues remain to be solved and also political and legal ones related, for instance, to data sharing and to different laws in different countries. Other issues related to communication to end-users and education, especially on the use of uncertainty. Overall, the progress is very important and the willingness of institutes and countries to join their efforts is increasing. Harmonization issues are still remaining, mainly due to differences in classifications or in laboratory standards between countries. However numerous initiatives are ongoing at the EU level and also at the global level. All these progress are scientifically stimulating and also promissing to provide tools to improve and monitor soil quality in countries, EU and at the global level.

Keywords: digital soil mapping, global soil mapping, national and European initiatives, global soil mapping products, mini-review

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Authors: Divya SY. Ang, Mark B. Tan, Nicholas EM. Yeo, Siti RB. Sudirman, Khong Yik Chew

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Introduction: The importance of the amalgamation of technological and engineering advances with surgical principles of reconstruction cannot be overemphasized. With earlier detection of cancer, consequences of high-speed living and neglect, like traumatic injuries and infection, resulting in increasingly younger patients with bone defects. This may result in malformations and suboptimal function that is more noticeable and palpable in the younger, active demographic. Our team proposes a technique that encapsulates a mesh of multidisciplinary effort, tissue engineering and reconstructive principles. Methods/Materials: Our patient was a young competitive footballer in his early 30s who was diagnosed with submandibular adenoid cystic carcinoma with bony involvement. He was thus counselled for a right hemi mandibulectomy, the floor of mouth resection, right selective neck dissection, tracheostomy, and free fibular flap reconstruction of his mandible and required post-operative radiotherapy. Being young and in his prime sportsman years, he was unable to accept the morbidities associated with using his fibula to reconstruct his mandible despite it being the gold standard reconstructive option. The fibula is an ideal vascularized bone flap because it’s reliable and easily shaped with relatively minimal impact on functional outcomes. The fibula contributes to 30% of weightbearing and is the attachment for the lateral compartment muscles; it is stronger in footballers concerning lateral bending. When harvesting the fibula, the distal 6-8cm and up to 10% of the total length is preserved to maintain the ankle’s stability, thus, minimizing the impact on daily activities. There are studies that have noted gait variability post-operatively. Therefore, returning to a premorbid competitive level may be doubtful. To improve his functional outcomes, the decision was made to try and restore the fibula's form and function. Using the concept of Fused Deposition Modelling (FDM), our team comprising of Plastics, Otolaryngology, Orthopedics and Radiology, worked with Osteopore to design a 3D bioresorbable implant to regenerate the fibula defect (14.5cm). Bone marrow was harvested via reaming the contralateral hip prior to the wide resection. 30mls of his blood was obtained for extracting platelet rich plasma. These were packed into the Osteopore 3D-printed bone scaffold. This was then secured into the fibula defect with titanium plates and screws. The flexor hallucis longus and soleus were anchored along the construct and intraosseous membrane, done in a single setting. Results: He was reviewed closely as an outpatient over 10 months post operatively. He reported no discernable loss or difference in ankle function. He is satisfied and back in training and our team has video and photographs that substantiate his progress. Conclusion: FDM allows regeneration of long bone defects. However, we aimed to also restore his eversion and inversion that is imperative for footballers and hence reattached his previously dissected muscles along the length of the Osteopore implant. We believe that the reattachment of the muscle stabilizes not only the construct but allows optimum muscle tensioning when moving his ankle. This is a simple but effective technique in restoring complete function and form in a young patient whose minute muscle control is imperative to life.

Keywords: fused deposition modelling, functional reconstruction, lower limb bony defects, regenerative surgery, 3D printing, tissue engineering

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Authors: Xingyu Gao, Qiang Wu, Yuanyuan Liu, Yue Yang

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In the era of the knowledge economy, the relationship between scientific knowledge and patents has garnered significant attention. Understanding the intricate interplay between the foundations of science and technological innovation has emerged as a pivotal challenge for both researchers and policymakers. This study establishes a coupled network of artificial intelligence patents based on co-cited scientific papers. Leveraging centrality metrics from network analysis offers a fresh perspective on understanding the influence of information flow and knowledge sharing within the network on patent impact. The study initially obtained patent numbers for 446,890 granted US AI patents from the United States Patent and Trademark Office’s artificial intelligence patent database for the years 2002-2020. Subsequently, specific information regarding these patents was acquired using the Lens patent retrieval platform. Additionally, a search and deduplication process was performed on scientific non-patent references (SNPRs) using the Web of Science database, resulting in the selection of 184,603 patents that cited 37,467 unique SNPRs. Finally, this study constructs a coupled network comprising 59,379 artificial intelligence patents by utilizing scientific papers co-cited in patent backward citations. In this network, nodes represent patents, and if patents reference the same scientific papers, connections are established between them, serving as edges within the network. Nodes and edges collectively constitute the patent coupling network. Structural characteristics such as node degree centrality, betweenness centrality, and closeness centrality are employed to assess the scientific connections between patents, while citation count is utilized as a quantitative metric for patent influence. Finally, a negative binomial model is employed to test the nonlinear relationship between these network structural features and patent influence. The research findings indicate that network structural features such as node degree centrality, betweenness centrality, and closeness centrality exhibit inverted U-shaped relationships with patent influence. Specifically, as these centrality metrics increase, patent influence initially shows an upward trend, but once these features reach a certain threshold, patent influence starts to decline. This discovery suggests that moderate network centrality is beneficial for enhancing patent influence, while excessively high centrality may have a detrimental effect on patent influence. This finding offers crucial insights for policymakers, emphasizing the importance of encouraging moderate knowledge flow and sharing to promote innovation when formulating technology policies. It suggests that in certain situations, data sharing and integration can contribute to innovation. Consequently, policymakers can take measures to promote data-sharing policies, such as open data initiatives, to facilitate the flow of knowledge and the generation of innovation. Additionally, governments and relevant agencies can achieve broader knowledge dissemination by supporting collaborative research projects, adjusting intellectual property policies to enhance flexibility, or nurturing technology entrepreneurship ecosystems.

Keywords: centrality, patent coupling network, patent influence, social network analysis

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Authors: Dominik Kowitzke

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Housing constructions have direct and indirect environmental impacts especially caused by soil sealing and gray energy consumption related to the use of construction materials. Accordingly, the German government introduced regulations limiting additional annual soil sealing. At the same time, in many regions like metropolitan areas the demand for further housing is high and of current concern in the media and politics. It is argued that meeting this demand by making better use of the existing housing supply is more sustainable than the construction of new housing units. In this context, targeting the phenomenon of so-called over the housing of empty nest households seems worthwhile to investigate for its potential to free living space and thus, reduce the need for new housing constructions and related environmental harm. Over housing occurs if no space adjustment takes place in household lifecycle stages when children move out from home and the space formerly created for the offspring is from then on under-utilized. Although in some cases the housing space consumption might actually meet households’ equilibrium preferences, frequently space-wise adjustments to the living situation doesn’t take place due to transaction or information costs, habit formation, or government intervention leading to increasing costs of relocations like real estate transfer taxes or tenant protection laws keeping tenure rents below the market price. Moreover, many detached houses are not long-term designed in a way that freed up space could be rent out. Findings of this research based on socio-economic survey data, indeed, show a significant difference between the living space of empty nest and a comparison group of households which never had children. The approach used to estimate the average difference in living space is a linear regression model regressing the response variable living space on a two-dimensional categorical variable distinguishing the two groups of household types and further controls. This difference is assumed to be the under-utilized space and is extrapolated to the total amount of empty nests in the population. Supporting this result, it is found that households that move, despite market frictions impairing the relocation, after children left their home tend to decrease the living space. In the next step, only for areas with tight housing markets in Germany and high construction activity, the total under-utilized space in empty nests is estimated. Under the assumption of full substitutability of housing space in empty nests and space in new dwellings in these locations, it is argued that in a perfect market with empty nest households consuming their equilibrium demand quantity of housing space, dwelling constructions in the amount of the excess consumption of living space could be saved. This, on the other hand, would prevent environmental harm quantified in carbon dioxide equivalence units related to average constructions of detached or multi-family houses. This study would thus provide information on the amount of under-utilized space inside dwellings which is missing in public data and further estimates the external effect of over housing in environmental terms.

Keywords: empty nests, environment, Germany, households, over housing

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Authors: Savvas Rogotis, Nikolaos Kalatzis, Stergios Dimou-Sakellariou, Nikolaos Marianos

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As precision holds the key for the introduction of distinct benefits in agriculture (e.g., energy savings, reduced labor costs, optimal application of inputs, improved products, and yields), it steadily becomes evident that new initiatives should focus on rendering Precision Agriculture (PA) more accessible to the average farmer. PA leverages on technologies such as the Internet of Things (IoT), earth observation, robotics and positioning systems (e.g., the Global Navigation Satellite System – GNSS - as well as individual positioning systems like GPS, Glonass, Galileo) that allow: from simple data georeferencing to optimal navigation of agricultural machinery to even more complex tasks like Variable Rate Applications. An identified customer pain point is that, from one hand, typical triangulation-based positioning systems are not accurate enough (with errors up to several meters), while on the other hand, high precision positioning systems reaching centimeter-level accuracy, are very costly (up to thousands of euros). Within this paper, a Ground-Based Augmentation System (GBAS) is introduced, that can be adapted to any existing IoT field-sensing station infrastructure. The latter should cover a minimum set of requirements, and in particular, each station should operate as a fixed, obstruction-free towards the sky, energy supplying unit. Station augmentation will allow them to function in pairs with GNSS rovers following the differential GNSS base-rover paradigm. This constitutes a key innovation element for the proposed solution that encompasses differential GNSS capabilities into an IoT field-sensing infrastructure. Integrating this kind of information supports the provision of several additional PA beneficial services such as spatial mapping, route planning, and automatic field navigation of unmanned vehicles (UVs). Right at the heart of the designed system, there is a high-end GNSS toolkit with base-rover variants and Real-Time Kinematic (RTK) capabilities. The GNSS toolkit had to tackle all availability, performance, interfacing, and energy-related challenges that are faced for a real-time, low-power, and reliable in the field operation. Specifically, in terms of performance, preliminary findings exhibit a high rover positioning precision that can even reach less than 10-centimeters. As this precision is propagated to the full dataset collection, it enables tractors, UVs, Android-powered devices, and measuring units to deal with challenging real-world scenarios. The system is validated with the help of Gaiatrons, a mature network of agro-climatic telemetry stations with presence all over Greece and beyond ( > 60.000ha of agricultural land covered) that constitutes part of “gaiasense” (www.gaiasense.gr) smart farming (SF) solution. Gaiatrons constantly monitor atmospheric and soil parameters, thus, providing exact fit to operational requirements asked from modern SF infrastructures. Gaiatrons are ultra-low-cost, compact, and energy-autonomous stations with a modular design that enables the integration of advanced GNSS base station capabilities on top of them. A set of demanding pilot demonstrations has been initiated in Stimagka, Greece, an area with a diverse geomorphological landscape where grape cultivation is particularly popular. Pilot demonstrations are in the course of validating the preliminary system findings in its intended environment, tackle all technical challenges, and effectively highlight the added-value offered by the system in action.

Keywords: GNSS, GBAS, precision agriculture, RTK, smart farming

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Authors: Meiling Yu, Nadia Rouatbi, Khuloud T. Al-Jamal

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Background: Treatment of neurological disorders with modern medical and surgical approaches remains difficult. Gene therapy, allowing the delivery of genetic materials that encodes potential therapeutic molecules, represents an attractive option. The treatment of brain diseases with gene therapy requires the gene-editing tool to be delivered efficiently to the central nervous system. In this study, we explored the efficiency of different delivery routes, namely intravenous (i.v.), intra-cranial (i.c.), and intra-nasal (i.n.), to deliver stable nucleic acid-lipid particles (SNALPs) containing gene-editing tools namely Cas9 mRNA and sgRNA encoding for GFP as a reporter protein. We hypothesise that SNALPs can reach the brain and perform gene-editing to different extents depending on the administration route. Intranasal administration (i.n.) offers an attractive and non-invasive way to access the brain circumventing the blood–brain barrier. Successful delivery of gene-editing tools to the brain offers a great opportunity for therapeutic target validation and nucleic acids therapeutics delivery to improve treatment options for a range of neurodegenerative diseases. In this study, we utilised Rosa26-Cas9 knock-in mice, expressing GFP, to study brain distribution and gene-editing efficiency of SNALPs after i.v.; i.c. and i.n. routes of administration. Methods: Single guide RNA (sgRNA) against GFP has been designed and validated by in vitro nuclease assay. SNALPs were formulated and characterised using dynamic light scattering. The encapsulation efficiency of nucleic acids (NA) was measured by RiboGreen™ assay. SNALPs were incubated in serum to assess their ability to protect NA from degradation. Rosa26-Cas9 knock-in mice were i.v., i.n., or i.c. administered with SNALPs to test in vivo gene-editing (GFP knockout) efficiency. SNALPs were given as three doses of 0.64 mg/kg sgGFP following i.v. and i.n. or a single dose of 0.25 mg/kg sgGFP following i.c.. knockout efficiency was assessed after seven days using Sanger Sequencing and Inference of CRISPR Edits (ICE) analysis. In vivo, the biodistribution of DiR labelled SNALPs (SNALPs-DiR) was assessed at 24h post-administration using IVIS Lumina Series III. Results: Serum-stable SNALPs produced were 130-140 nm in diameter with ~90% nucleic acid loading efficiency. SNALPs could reach and stay in the brain for up to 24h following i.v.; i.n. and i.c. administration. Decreasing GFP expression (around 50% after i.v. and i.c. and 20% following i.n.) was confirmed by optical imaging. Despite the small number of mice used, ICE analysis confirmed GFP knockout in mice brains. Additional studies are currently taking place to increase mice numbers. Conclusion: Results confirmed efficient gene knockout achieved by SNALPs in Rosa26-Cas9 knock-in mice expressing GFP following different routes of administrations in the following order i.v.= i.c.> i.n. Each of the administration routes has its pros and cons. The next stages of the project involve assessing gene-editing efficiency in wild-type mice and replacing GFP as a model target with therapeutic target genes implicated in Motor Neuron Disease pathology.

Keywords: CRISPR, nanoparticles, brain diseases, administration routes

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Authors: Roven Tumaneng, Angelica Kristina Monzon, Ralph Sedricke Lapuz, Jose Don De Alban, Jennica Paula Masigan, Joanne Rae Pales, Laila Monera Pornel, Dennis Tablazon, Rizza Karen Veridiano, Jackie Lou Wenceslao, Edmund Leo Rico, Neil Aldrin Mallari

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Most protected area management plans in the Philippines, particularly the smaller and more remote islands suffer from insufficient baseline data, which should provide the bases for formulating measureable conservation targets and appropriate management interventions for these protected areas. Attempts to synthesize available data particularly on cultural and socio-economic characteristic of local peoples within and outside protected areas also suffer from the lack of comprehensive and detailed inventories, which should be considered in designing adaptive management interventions to be used for those protected areas. Mt Guiting-guiting Natural Park (MGGNP) located in Sibuyan Island is one of the poorly studied protected areas in the Philippines. In this study, we determined the highly biologically important areas of the protected area using Maximum Entropy approach (MaxEnt) from environmental predictors (i.e., topographic, bioclimatic,land cover, and soil image layers) derived from global remotely sensed data and point occurrence data of species of birds and trees recorded during field surveys on the island. A total of 23 trigger species of birds and trees was modeled and stacked to generate species richness maps for biological high conservation value areas (HCVAs). Forest habitat change was delineated using dual-polarised L-band ALOS-PALSAR mosaic data at 25 meter spatial resolution, taken at two acquisition years 2007 and 2009 to provide information on forest cover ad habitat change in the island between year 2007 and 2009. Determining the livelihood guilds were also conducted using the data gathered from171 household interviews, from which demographic and livelihood variables were extracted (i.e., age, gender, number of household members, educational attainment, years of residency, distance from forest edge, main occupation, alternative sources of food and resources during scarcity months, and sources of these alternative resources).Using Principal Component Analysis (PCA) and Kruskal-Wallis test, the diversity and patterns of forest resource use by people in the island were determined with particular focus on the economic activities that directly and indirectly affect the population of key species as well as to identify levels of forest resource use by people in different areas of the park.Results showed that there are gaps in the area occupied by the natural park, as evidenced by the mismatch of the proposed HCVAs and the existing perimeters of the park. We found out that subsistence forest gathering was the possible main driver for forest degradation out of the eight livelihood guilds that were identified in the park. Determining the high conservation areas and identifyingthe anthropogenic factors that influence the species richness and abundance of key species in the different management zone of MGGNP would provide guidance for the design of a protected area management plan and future monitoring programs. However, through intensive communication and consultation with government stakeholders and local communities our results led to setting conservation targets in local development plans and serve as a basis for the reposition of the boundaries and reconfiguration of the management zones of MGGNP.

Keywords: conservation gaps, livelihood guilds, MaxEnt, protected area

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Authors: Shpetim Rezniqi

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Financial Policies in the process of global crisis the current crisis has swept the world with special emphasis, most developed countries, those countries which have most gross -product world and you have a high level of living.Even those who are not experts can describe the consequences of the crisis to see the reality that is seen, but how far will it go this crisis is impossible to predict. Even the biggest experts have conjecture and large divergence, but agree on one thing: - The devastating effects of this crisis will be more severe than ever before and can not be predicted.Long time, the world was dominated economic theory of free market laws. With the belief that the market is the regulator of all economic problems. The market, as river water will flow to find the best and will find the necessary solution best. Therefore much less state market barriers, less state intervention and market itself is an economic self-regulation. Free market economy became the model of global economic development and progress, it transcends national barriers and became the law of the development of the entire world economy. Globalization and global market freedom were principles of development and international cooperation. All international organizations like the World Bank, states powerful economic, development and cooperation principles laid free market economy and the elimination of state intervention. The less state intervention much more freedom of action was this market- leading international principle. We live in an era of financial tragic. Financial markets and banking in particular economies are in a state of thy good, US stock markets fell about 40%, in other words, this time, was one of the darkest moments 5 since 1920. Prior to her rank can only "collapse" of the stock of Wall Street in 1929, technological collapse of 2000, the crisis of 1973 after the Yom Kippur war, while the price of oil quadrupled and famous collapse of 1937 / '38, when Europe was beginning World war II In 2000, even though it seems like the end of the world was the corner, the world economy survived almost intact. Of course, that was small recessions in the United States, Europe, or Japan. Much more difficult the situation was at crisis 30s, or 70s, however, succeeded the world. Regarding the recent financial crisis, it has all the signs to be much sharper and with more consequences. The decline in stock prices is more a byproduct of what is really happening. Financial markets began dance of death with the credit crisis, which came as a result of the large increase in real estate prices and household debt. It is these last two phenomena can be matched very well with the gains of the '20s, a period during which people spent fists as if there was no tomorrow. All is not away from the mouth of the word recession, that fact no longer a sudden and abrupt. But as much as the financial markets melt, the greater is the risk of a problematic economy for years to come. Thus, for example, the banking crisis in Japan proved to be much more severe than initially expected, partly because the assets which were based more loans had, especially the land that falling in value. The price of land in Japan is about 15 years that continues to fall. (ADRI Nurellari-Published in the newspaper "Classifieds"). At this moment, it is still difficult to çmosh to what extent the crisis has affected the economy and what would be the consequences of the crisis. What we know is that many banks will need more time to reduce the award of credit, but banks have this primary function, this means huge loss.

Keywords: globalisation, finance, crisis, recomandation, bank, credits

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Authors: Fernanda Piculo, Giovana Vesentini, Gabriela Marini, Debora Cristina Damasceno, Angelica Mercia Pascon Barbosa, Marilza Vieira Cunha Rudge

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Introduction: Women with previous gestational diabetes mellitus (GDM) were significantly more likely to have urinary incontinence (UI) and pelvic floor muscle dysfunction compared to non-diabetic women two years after a cesarean section. Additional results demonstrated that induced diabetes causes detrimental effects on pregnant rat urethral muscle. These results indicate the need for exploration of the mechanistic role of a recovery factor in female UI. Chemokine ligand 7 (CCL7) was significantly over expressed in rat serum, urethral and vaginal tissues immediately following induction of stress UI in a rat model simulating birth trauma. CCL7 over expression has shown potency for stimulating targeted stem cell migration and provide a translational link (clinical measurement) which further provide opportunities for treatment. The aim of this study was to investigate the CCL7 levels profile in diabetic pregnant women with urinary incontinence during pregnancy over the first year postpartum. Methods: This study was conducted in the Perinatal Diabetes Research Center of the Botucatu Medical School/UNESP, and was approved by the Research Ethics Committee of the Institution (CAAE: 20639813.0.0000.5411). The diagnosis of GDM was established between 24th and 28th gestational weeks, by the 75 g-OGTT test according to ADA’s criteria. Urinary incontinence was defined according to the International Continence Society and the CCL7 levels was measured by ELISA (R&D Systems, Catalog Number DCC700). Two hundred twelve women were classified into four study groups: normoglycemic continent (NC), normoglycemic incontinent (NI), diabetic continent (DC) and diabetic incontinent (DI). They were evaluated at six-time-points: 12-18, 24-28 and 34-38 gestational weeks, 24-48 hours, 6 weeks and 6-12 months postpartum. Results: At 12-18 weeks, it was possible to consider only two groups, continent and incontinent, because at this early gestational period has not yet been the diagnosis of GDM. The group with GDM and UI (DI group) showed lower levels of CCL7 in all time points during pregnancy and postpartum, compared to normoglycemic groups (NC and NI), indicating that these women have not recovered from child birth induced UI during the 6-12 months postpartum compared to their controls, and that the progression of UI and/or lack of recovery throughout the first postpartum year can be related with lower levels of CCL7. Instead, serum CCL7 was significantly increased in the NC group. Taken together, these findings of overexpression of CCL7 in the NC group and decreased levels in the DI group, could confirm that diabetes delays the recovery from child birth induced UI, and that CCL7 could potentially be used as a serum marker of injury. Conclusion: This study demonstrates lower levels of CCL7 in the DI group during pregnancy and postpartum and suggests that the progression of UI in diabetic women and/or lack of recovery throughout the first postpartum year can be related with low levels of CCL7. This provides a translational potential where CCL7 measurement could be used as a surrogate for injury after delivery. Successful controlled CCL7 mediated stem cell homing to the lower urinary tract could one day introduce the potential for non-operative treatment or prevention of stress urinary incontinence.

Keywords: CCL7, gestational diabetes, pregnancy, urinary incontinence

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Authors: Ram Sharma, Esha Chatterjee, Santosh Kumar Guru, Kunal Nepali

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A tractable anti-lung cancer agent was identified via the installation of a Ring C expanded synthetic analogue of the alkaloid vasicinone [7,8,9,10-tetrahydroazepino[2,1-b] quinazolin-12(6H)-one (TAZQ)] as a surface recognition part in the HDAC inhibitory three-component model. Noteworthy to mention that the candidature of TAZQ was deemed suitable for accommodation in HDAC inhibitory pharmacophore as per the results of the fragment recruitment process conducted by our laboratory. TAZQ was pinpointed through the fragment screening program as a synthetically flexible fragment endowed with some moderate cell growth inhibitory activity against the lung cancer cell lines, and it was anticipated that the use of the aforementioned fragment to generate hydroxamic acid functionality (zinc-binding motif) bearing HDAC inhibitors would boost the antitumor efficacy of TAZQ. Consistent with our aim of applying epigenetic targets to the treatment of lung cancer, a strikingly potent anti-lung cancer scaffold (compound 6) was pinpointed through a series of in-vitro experiments. Notably, the compounds manifested a magnificent activity profile against KRAS and EGFR mutant lung cancer cell lines (IC50 = 0.80 - 0.96 µM), and the effects were found to be mediated through preferential HDAC6 inhibition (IC50 = 12.9 nM). In addition to HDAC6 inhibition, the compounds also elicited HDAC1 and HDAC3 inhibitory activity with an IC50 value of 49.9 nM and 68.5 nM, respectively. The HDAC inhibitory ability of compound 6 was also confirmed from the results of the western blot experiment that revealed its potential to decrease the expression levels of HDAC isoforms (HDAC1, HDAC3, and HDAC6). Noteworthy to mention that complete downregulation of the HDAC6 isoform was exerted by compound 6 at 0.5 and 1 µM. Moreover, in another western blot experiment, treatment with hydroxamic acid 6 led to upregulation of H3 acK9 and α-Tubulin acK40 levels, ascertaining its inhibitory activity toward both the class I HDACs and Class II B HDACs. The results of other assays were also encouraging as treatment with compound 6 led to the suppression of the colony formation ability of A549 cells, induction of apoptosis, and increase in autophagic flux. In silico studies led us to rationalize the results of the experimental assay, and some key interactions of compound 6 with the amino acid residues of HDAC isoforms were identified. In light of the impressive activity spectrum of compound 6, a pH-responsive nanocarrier (hyaluronic acid-compound 6 nanoparticles) was prepared. The dialysis bag approach was used for the assessment of the nanoparticles under both normal and acidic circumstances, and the pH-sensitive nature of hyaluronic acid-compound 6 nanoparticles was confirmed. Delightfully, the nanoformulation was devoid of cytotoxicity against the L929 mouse fibroblast cells (normal settings) and exhibited selective cytotoxicity towards the A549 lung cancer cell lines. In a nutshell, compound 6 appears to be a promising adduct, and a detailed investigation of this compound might yield a therapeutic for the treatment of lung cancer.

Keywords: HDAC inhibitors, lung cancer, scaffold, hyaluronic acid, nanoparticles

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Authors: Milica Carević, Katarina Banjanac, Marija ĆOrović, Ana Milivojević, Nevena Prlainović, Aleksandar Marinković, Dejan Bezbradica

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Nowadays, considering the growing awareness of functional food beneficial effects on human health, due attention is dedicated to the research in the field of obtaining new prominent products exhibiting improved physiological and physicochemical characteristics. Therefore, different approaches to valuable bioactive compounds synthesis have been proposed. β-Galactosidase, for example, although mainly utilized as hydrolytic enzyme, proved to be a promising tool for these purposes. Namely, under the particular conditions, such as high lactose concentration, elevated temperatures and low water activities, reaction of galactose moiety transfer to free hydroxyl group of the alternative acceptor (e.g. different sugars, alcohols or aromatic compounds) can generate a wide range of potentially interesting products. Up to now, galacto-oligosaccharides and lactulose have attracted the most attention due to their inherent prebiotic properties. The goal of this study was to obtain a novel product sorbitol galactoside, using the similar reaction mechanism, namely transgalactosylation reaction catalyzed by β-galactosidase from Aspergillus oryzae. By using sugar alcohol (sorbitol) as alternative acceptor, a diverse mixture of potential prebiotics is produced, enabling its more favorable functional features. Nevertheless, an introduction of alternative acceptor into the reaction mixture contributed to the complexity of reaction scheme, since several potential reaction pathways were introduced. Therefore, the thorough optimization using response surface method (RSM), in order to get an insight into different parameter (lactose concentration, sorbitol to lactose molar ratio, enzyme concentration, NaCl concentration and reaction time) influences, as well as their mutual interactions on product yield and productivity, was performed. In view of product yield maximization, the obtained model predicted optimal lactose concentration 500 mM, the molar ratio of sobitol to lactose 9, enzyme concentration 0.76 mg/ml, concentration of NaCl 0.8M, and the reaction time 7h. From the aspect of productivity, the optimum substrate molar ratio was found to be 1, while the values for other factors coincide. In order to additionally, improve enzyme efficiency and enable its reuse and potential continual application, immobilization of β-galactosidase onto tailored silica nanoparticles was performed. These non-porous fumed silica nanoparticles (FNS)were chosen on the basis of their biocompatibility and non-toxicity, as well as their advantageous mechanical and hydrodinamical properties. However, in order to achieve better compatibility between enzymes and the carrier, modifications of the silica surface using amino functional organosilane (3-aminopropyltrimethoxysilane, APTMS) were made. Obtained support with amino functional groups (AFNS) enabled high enzyme loadings and, more importantly, extremely high expressed activities, approximately 230 mg proteins/g and 2100 IU/g, respectively. Moreover, this immobilized preparation showed high affinity towards sorbitol galactoside synthesis. Therefore, the findings of this study could provided a valuable contribution to the efficient production of physiologically active galactosides in immobilized enzyme reactors.

Keywords: β-galactosidase, immobilization, silica nanoparticles, transgalactosylation

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