Search results for: alkali activation

Authors: Yan Wang, Wei Wu

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In recent years, with the gradual change of Chinese urban development mode from 'incremental development' to 'stock-based renewal', the urban design method of ‘grand scene’ in the past could only cope with the planning and construction of incremental spaces such as new towns and new districts, while the problems involved in the renewal of the stock lands such as historic blocks of ancient cities are more complex. 'Simplified' large-scale demolition and construction may lead to the damage of the ancient city's texture and the overall cultural atmosphere; thus it is necessary to re-explore the urban design path of historical blocks in the conservation context of the ancient city. Through the study of the cultural context of the ancient city of Suzhou in China and the interpretation of its current characteristics, this paper explores the methods and paths for the renewal of historical and cultural blocks in the ancient city. It takes No. 12 and No. 13 historical blocks in the ancient city of Suzhou as examples, coordinating the spatial layout and the landscape and shaping the regional characteristics to improve the quality of the ancient city's life. This paper analyses the idea of conservation and regeneration from the aspects of culture, life, business form, and transport. Guided by the planning concept of ‘block repair and cultural infiltration’, it puts forward the urban design path of ‘conservation priority, activation and utilization, organic renewal and strengthening guidance’, with a view to continuing the cultural context and stimulating the vitality of ancient city, so as to realize the integration of history, modernity, space and culture. As a rare research on urban design in the scope of Suzhou ancient city, the paper expects to explore the concepts and methods of urban design for the historic blocks on the basis of the conservation of the history, space, and culture and provides a reference for other similar types of urban construction.

Keywords: historical block, Suzhou ancient city, stock-based renewal, urban design

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Authors: R. Stalin, D. Karthick, H. Haseena Banu, T. P. Sachidanandam, P. Shanthi

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Background: Breast cancer is emerging as one of the leading cause of cancer related deaths and hence there arises the need to look out for drugs which are more targets specific with minimal side effects. In recent times, there is a shift towards alternative medicine due to low cost and less side effects. Siddha system of medicine is one the oldest system of medicine practiced against various ailments. Tridham (TD) is a herbal formulation prepared in our laboratory consisting of Terminalia chebula, Elaeocarpus ganitrus and Prosopis cineraria in a definite ratio (TD) and its anticancer potential is evaluated in terms of induction of apoptosis. Objective: The present study was designed to investigate the anti proliferative effect of TD and 1,2,3,4,6-penta-O-galloyl-b-D-glucose (PGG), a pure compound isolated from TD on human mammary carcinoma cell line (MCF-7). Materials and Methods: Cell viability was studied using MTT analysis and trypan blue staining. Mitochondrial membrane potential was studied using DAPI staining. The protein and mRNA expressions of pro-apoptotic and anti- apoptotic markers namely Bax, Bad, Bcl-2 and caspases were also assessed by Western Blotting and RT PCR. Results: Viability studies of TD and PGG treated MCF-7 cells showed an inhibition in cell growth in time and dose dependent manner. The alteration in mitochondrial membrane potential was restored through treatment with TD and PGG which was confirmed by DAPI staining. The protein and mRNA expression of pro-apoptotic markers was found to be significantly increased in TD and PGG treated cells with a concomitant decrease in anti-apoptotic markers. Conclusion: The results of the study suggest that TD and PGG exhibit their anticancer effect through its membrane stabilizing property and activation of apoptotic cascade in MCF-7 cells.

Keywords: apoptosis, mammary carcinoma, MCF-7, penta galloyl glucose, Tridham

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Authors: A. Barratt, M. H. Granat, S. Buttress, B. Roy

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Introduction: Physiotherapy is an essential part of the treatment of patients with shoulder problems. The focus of treatment is usually centred on addressing specific physiotherapy goals, ultimately resulting in the improvement in pain and function. This study investigates if computerised physiotherapy using gamification principles are as effective as standard physiotherapy. Methods: Physiotherapy exergames were created using a combination of commercially available hardware, the Microsoft Kinect, and bespoke software. The exergames used were validated by mapping physiotherapy goals of physiotherapy which included; strength, range of movement, control, speed, and activation of the kinetic chain. A multicenter, randomised prospective controlled trial investigated the use of exergames on patients with Shoulder Impingement Syndrome who had undergone Arthroscopic Subacromial Decompression surgery. The intervention group was provided with the automated sensor-based technology, allowing them to perform exergames and track their rehabilitation progress. The control group was treated with standard physiotherapy protocols. Outcomes from different domains were used to compare the groups. An important metric was the assessment of shoulder range of movement pre- and post-operatively. The range of movement data included abduction, forward flexion and external rotation which were measured by the software, pre-operatively, 6 weeks and 12 weeks post-operatively. Results: Both groups show significant improvement from pre-operative to 12 weeks in elevation in forward flexion and abduction planes. Results for abduction showed an improvement for the interventional group (p < 0.015) as well as the test group (p < 0.003). Forward flexion improvement was interventional group (p < 0.0201) with the control group (p < 0.004). There was however no significant difference between the groups at 12 weeks for abduction (p < 0.118067) , forward flexion (p < 0.189755) or external rotation (p < 0.346967). Conclusion: Exergames may be used as an alternative to standard physiotherapy regimes; however, further analysis is required focusing on patient engagement.

Keywords: shoulder, physiotherapy, exergames, gamification

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Authors: Niharika Keot, Manabendra Sarma

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A thorough investigation of Ln3+ complexes with more than one inner-sphere water molecule is crucial for designing high relaxivity contrast agents (CAs) used in magnetic resonance imaging (MRI). This study accomplished a comparative stability analysis of two hexadentate (H3cbda and H3dpaa) and two heptadentate (H4peada and H3tpaa) ligands with Ln3+ ions. The higher stability of the hexadentate H3cbda and heptadentate H4peada ligands has been confirmed by the binding affinity and Gibbs free energy analysis in aqueous solution. In addition, energy decomposition analysis (EDA) reveals the higher binding affinity of the peada4− ligand than the cbda3− ligand towards Ln3+ ions due to the higher charge density of the peada4− ligand. Moreover, a mechanistic overview of water exchange kinetics has been carried out based on the strength of the metal–water bond. The strength of the metal–water bond follows the trend Gd–O47 (w) > Gd–O39 (w) > Gd–O36 (w) in the case of the tris-aquated [Gd(cbda)(H2O)3] and Gd–O43 (w) > Gd–O40 (w) for the bis-aquated [Gd(peada)(H2O)2]− complex, which was confirmed by bond length, electron density (ρ), and electron localization function (ELF) at the corresponding bond critical points. Our analysis also predicts that the activation energy barrier decreases with the decrease in bond strength; hence kex increases. The 17O and 1H hyperfine coupling constant values of all the coordinated water molecules were different, calculated by using the second-order Douglas–Kroll–Hess (DKH2) approach. Furthermore, the ionic nature of the bonding in the metal–ligand (M–L) bond was confirmed by the Quantum Theory of Atoms-In-Molecules (QTAIM) and ELF along with energy decomposition analysis (EDA). We hope that the results can be used as a basis for the design of highly efficient Gd(III)-based high relaxivity MRI contrast agents for medical applications.

Keywords: MRI contrast agents, lanthanide chemistry, thermodynamic stability, water exchange kinetics

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Authors: Lívia Pimentel Sant'ana Dourado, Raquel Das Neves Almeida, Luís Henrique Costa Corrêa Neto, Nayara Soares, Kelly Grace Magalhães

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Introduction: Obesity and high-fat diet intake have a crucial impact on immune cells and inflammatory profile, highlighting an emerging realization that obesity is an inflammatory disease. In the present work, we aimed to characterize the role of caspase-1/11 and NLRP3 inflammasome in the establishment of mice obesity and modulation of inflammatory lipid metabolism induced by high fat diet intake. Methods and results: Wild type, caspase-1/11 and NLRP3 knockout mice were fed with standard fat diet (SFD) or high fat diet (HFD) for 90 days. The weight of animals was measured weekly to monitor the weight gain. After 90 days, the blood, peritoneal lavage cells, heart and liver were collected from mice studied here. Cytokines were measured in serum by ELISA and analyzed in spectrophotometry. Lipid antigen presentation molecule CD1d expression, reactive oxygen species (ROS) generation and lipid droplets biogenesis were analyzed in cells from mice peritoneal cavity by flow cytometry. Liver histopathology was performed for morphological evaluation of the organ. The absence of caspase-1/11, but not NLRP3, in mice fed with HFD favored the mice weight gain, increased liver size, induced development of hepatic steatosis and IL-12 secretion in mice compared to mice fed with SFD. In addition, caspase-1/11 knockout mice fed with HFD presented an increased CD1d molecule expression, as well as higher levels of lipid droplets biogenesis and ROS generation compared to wild type mice also fed with HFD. Conclusion: Our data suggest that caspase-1/11 knockout mice have greater susceptibility to obesity as well as increased activation of lipid metabolism and inflammatory markers.

Keywords: caspase 1, caspase 11, inflamassome, obesity, lipids

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Authors: M. Nazem Salimi, C. Abrinia, M. Baniassadi, M. Ehsani

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Mechanical properties of epoxy based nanocomposites containing copper coated MWCNTs were investigated and a comparative study between nanocomposites containing functionalized MWCNTs and copper coated MWCNTs which are already functionalized was conducted. The MWCNTs was deposited with copper nanoparticles through electroless deposition process after accomplishment of "two-step" method as sensitization and activation procedures on oxidized MWCNTs. In addition, functionalization of MWCNTs was carried out through combination of two covalent and non-covalent funcionalization methods using HNO3 for acid solution of covalent treatment and Triton X100 as non-ionic surfactant of non-covalent treatment. The presence of functional groups and removal of impurities of MWCNTs were confirmed by FTIR and Raman spectroscopy, respectively. The layer of copper nanoparticles on the MWCNTs wall increasing its diameter was observed by SEM. Utilizing solution blending process, 0.1%, 0.5% and 1.5% wt loading of both copper coated MWCNTs and non-coated MWCNTs were used to prepare epoxy-based nanocomposites. The tensile, flexural and impact properties of nanocomposites were investigated. The results of tensile test demonstrated that nanocomposites containing copper coated MWCNTs exhibited brittle behavior compared to those reinforced with functionalized MWCNTs, whereas former one exhibited higher values of modulus than latter one for concentrations more than 0.4% wt. Presence of copper particles on MWCNTs surface decreased the tensile strength of nanocomposites. In comparison to pure epoxy, nanocomposites with treated-MWCNTs and Cu-MWCNTs loading of 0.1% wt showed an increase of 35% and 51.6% for flexural strength beside 20% and 30% increase in flexural modulus, respectively, whereas flexural properties of both naocomposites decreased with increasing of CNTs concentration. The results of impact strength of nanocomposites with Cu-CNTs demonstrated that impact properties decreased with increasing of filler content with a optimum value at 0.1% wt while in high concentrations impact properties of Cu-nanocomposites exhibited lower values than f-MWCNT nanocomposites.

Keywords: epoxyresin, nanocomposite, functionalization, copper, electroless deposition process, mechanical properties

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Authors: Kinjal H. Shah, Piyush M. Patel

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Diabetes mellitus is considered to be a serious endocrine syndrome. Synthetic hypoglycemic agents can produce serious side effects including hematological effects, coma, and disturbances of the liver and kidney. In addition, they are not suitable for use during pregnancy. In recent years, there have been relatively few reports of short-term side effects or toxicity due to sulphonylureas. Published figures and frequency of side effects in large series of patient range from about 1 to 5%, with symptoms severe enough to lead to the withdrawal of the drug in less than 1 to 2%. Adverse effects, in general, have been of the following type: allergic skin reactions, gastrointestinal disturbances, blood dyscrasias, hepatic dysfunction, and hypoglycemia. The associated disadvantages with insulin and oral hypoglycemic agents have led to stimulation in the research for locating natural resources showing antidiabetic activity and to explore the possibilities of using traditional medicines with proper chemical and pharmacological profiles. Literature survey reveals that the inhabitants of Abbottabad district of Pakistan use the dried leaf powder along with table salt and water orally for treating diabetes, skin allergy, wounds and as a blood purifier, where they pronounced the plant locally as ‘Nem.' The detailed phytochemical investigation of the Cedrela toona Roxb. leaves for antidiabetic activity has not been documented. Hence, there is a need for phytochemical investigation of the leaves for antidiabetic activity. The collection of fresh leaves and authentification followed by successive extraction, phytochemical screening, and testing of antidiabetic activity. The blood glucose level was reduced maximum in ethanol extract at 5th and 7th h after treatment. Blood glucose was depressed by 8.2% and 10.06% in alloxan – induced diabetic rats after treatment which was comparable to the standard drug, Glibenclamide. This may be due to the activation of the existing pancreatic cells in diabetic rats by the ethanolic extract.

Keywords: antidiabetic, Cedrela toona Roxb., phytochemical screening, blood glucose

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Authors: Seyyed Mohammad Amin Mousavi Sagharchi, Elham Javanroudi

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Introduction: Tuberculosis (TB) is a known disease with hidden features caused by Mycobacterium tuberculosis (MTB). This disease, which is one of the 10 deadliest in the world, has caused millions of deaths in recent decades. Furthermore, TB is responsible for infecting about 30% population of world. Like any infection, TB can activate the immune system by locating and colonization in the human body, especially in the alveoli. TB is granulomatosis, so MTB can absorb the host’s immune cells and other cells to form granuloma. Method: Different databases (e.g., PubMed) were recruited to prepare this paper and fulfill our goals to search and find effective papers and investigations. Results: Immune response to MTB is related to T cell killers and contains CD1, CD4, and CD8 T lymphocytes. CD1 lymphocytes can recognize glycolipids, which highly exist in the Mycobacterial fatty cell wall. CD4 lymphocytes and macrophages form granuloma, and it is the main line of immune response to Mycobacteria. On the other hand, CD8 cells have cytolytic function for directly killing MTB by secretion of granulysin. Other functions and secretion to the deal are interleukin-12 (IL-12) by induction of expression interferon-γ (INF-γ) for macrophages activation and creating a granuloma, and tumor necrosis factor (TNF) by promoting macrophage phagolysosomal fusion. Conclusion: Immune cells in battle with MTB are macrophages, dendritic cells (DCs), neutrophils, and natural killer (NK) cells. These immune cells can recognize the Mycobacterium by various receptors, including Toll-like receptors (TLRs), Nod-like receptors (NLRs), and C-type lectin receptors (CLRs) located in the cell surface. In human alveoli exist about 50 dendritic macrophages, which have close communication with other immune cells in the circulating system and epithelial cells to deal with Mycobacteria. Against immune cells, MTB handles some factors (e.g., cordfactor, O-Ag, lipoarabinomannan, sulfatides, and adenylate cyclase) and practical functions (e.g., inhibition of macrophages).

Keywords: mycobacterium tuberculosis, immune responses, immunological mechanisms, respiratory tuberculosis

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Authors: Michael Scott Evans, Andrew Smith

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The feeling of fatigue at work could potentially have devastating consequences. The aim of this study was to investigate whether the well-established objective indicator of fatigue – the Fatigue Risk Index (FRI) calculator used by the rail industry is an effective indicator to the number of safety incidents, in which fatigue could have been a contributing factor. The study received ethics approval from Cardiff University’s Ethics Committee (EC.16.06.14.4547). A total of 901 safety incidents were recorded from a single British rail franchise between 1st June 2010 – 31st December 2016, into the Safety Management Information System (SMIS). The safety incident types identified that fatigue could have been a contributing factor were: Signal Passed at Danger (SPAD), Train Protection & Warning System (TPWS) activation, Automatic Warning System (AWS) slow to cancel, failed to call, and station overrun. From the 901 recorded safety incidents, the scheduling system CrewPlan was used to extract the Fatigue Index (FI) score and Risk Index (RI) score of all train drivers on the day of the safety incident. Only the working rosters of 64.2% (N = 578) (550 men and 28 female) ranging in age from 24 – 65 years old (M = 47.13, SD = 7.30) were accessible for analyses. Analysis from all 578 train drivers who were involved in safety incidents revealed that 99.8% (N = 577) of Fatigue Index (FI) scores fell within or below the identified guideline threshold of 45 as well as 97.9% (N = 566) of Risk Index (RI) scores falling below the 1.6 threshold range. Their scores represent good practice within the rail industry. These findings seem to indicate that the current objective indicator, i.e. the FRI calculator used in this study by the British rail franchise was not an effective predictor of train driver’s FI scores and RI scores, as safety incidents in which fatigue could have been a contributing factor represented only 0.2% of FI scores and 2.1% of RI scores. Further research is needed to determine whether there are other contributing factors that could provide a better indication as to why there is such a significantly large proportion of train drivers who are involved in safety incidents, in which fatigue could have been a contributing factor have such low FI and RI scores.

Keywords: fatigue risk index calculator, objective indicator of fatigue, rail industry, safety incident

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Authors: Giorgi Chichinadze, David Shengelia, Tamara Tsutsunava, Nikoloz Maisuradze, Giorgi Beridze

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The Jalovchat gabbro intrusive is exposed on the northern and southern slopes of Main Range zone of the Greater Caucasus, on an area about 25km2. It is intruded in Precambrian crystalline schists and amphibolites intensively metamorphose them along the contact zone. The intrusive is represented by hornblende-bearing gabbro, gabbro-norites and norites including thin vein bodies of gabbro-pegmatites, anorthosites and micro-gabbros. Especially should be noted the veins of gabbro-pegmatites with the gigantic (up to 0.5m) hornblende crystals. From this point of view, the Jalovchat gabbroid intrusive is particularly interesting and by its unusual composition has no analog in the Caucasus overall. The comprehensive petrologic and geochemical study of the intrusive was carried out by the authors. The results of investigations are following. Amphiboles correspond to magnesiohastingsite and magnesiohornblende. In hastingsite and hornblende as a result of isovalent isomorphism of Fe2+ by Mg, content of the latter has been increased. By AMF and Na20+K diagrams the intrusive rocks correspond to tholeiitic basalts or to basalts close to it by composition. According to ACM-AMF double diagram the samples distributed in the fields of MORB and alkali cumulates. In TiO2/FeO+Fe2O3, Zr/Y-Zr and Ti-Cr/Ni diagrams and Ti-Cr-Y triangular diagram samples are arranged in the fields of island-arc and mid-oceanic basalts or along the trends reflecting mid-oceanic ridges or island arcs. K2O/TiO2 diagram shows that these rocks belong to normal and enriched MORB type. According to Th/Nb/Y ratio, the Jalovchat intrusive composition corresponds to depleted mantle, but by Sm/Y-Ce/Sm - to the MORB area. Th/Y and Nb/Y ratios coincide with the MORB composition, Th/Yb-Ta/Yb and La/Nb-Ti ratios correspond to N MORB, and Rb/Y and N/Y - to the lower crust formations. Exceptional are Ce/Pb-Ce and Nb/Th-Nb diagrams, showing the area of primitive mantle. Spidergrams are characterized by almost horizontal trend, weakly expressed Eu minimums and by a slight depletion of light REE. Similar are characteristic of typical tholeiit basalts. In comparison to MORB spidergrams, they are characterized by depletion of light REE. Their correlation to the spidergrams of Jalovchat intrusive proves that they are more depleted. The above cited points to the gradual depletion of mantle with the light REE in geological time. The RE and REE diagrams reveal unexpected regularity. In particular, petro-geochemical characteristics of Jalovchat gabbroid intrusive predominantly correspond to MORB, that usually is an anomalous phenomenon, since in ‘ophiolitic’ section magmatic formations represented mainly by gigantic prismatic hornblende-bearing gabbro and gabbro-pegmatite are not indicated. On the basis of petro-mineralogical and petro-geochemical data analysis, the authors consider that the Jalovchat intrusive belongs to the subduction geodynamic type. In the depleted mantle rich in water the MORB rock system has subducted, where the favorable conditions for crystallization of hornblende and especially for its gigantic crystals occurred. It is considered that the Jalovchat intrusive was formed in deep horizons of the Earth’s crust as a result of crystallization of water-bearing Bajocian basalt magma.

Keywords: The Greater Caucasus, gabbro-pegmatite, hornblende-bearing gabbro, petrogenesis

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Authors: Ambrish Tiwari, Sudhasini Panda, Archana Singh, Kalpana Luthra, S. K. Sharma

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Introduction: On the basis of available literature we know that various host factors play a role in outcome of Tuberculosis (TB) infection by modulating innate immunity. One such factor is Inducible Nitric Oxide Synthase enzyme (iNOS) which help in the production of Nitric Oxide (NO), an antimicrobial agent. Expression of iNOS is in control of various host factors in which Vitamin D along with its nuclear receptor Vitamin D receptor (VDR) is one of them. Vitamin D along with its receptor also produces cathelicidin (antimicrobicidal agent). With this background, we attempted to investigate the levels of Vitamin D and NO along with their associated molecules in tuberculosis patients and household contacts as compared to healthy controls and assess the implication of these findings in susceptibility to tuberculosis (TB). Study subjects and methods: 100 active TB patients, 75 household contacts, and 70 healthy controls were taken. VDR and iNOS mRNA levels were studied using real-time PCR. Serum VDR, cathelicidin, iNOS levels were measured using ELISA. Serum Vitamin D levels were measured in serum samples using chemiluminescence based immunoassay. NO was measured using colorimetry based kit. Results: VDR and iNOS mRNA levels were found to be lower in active TB group compared to household contacts and healthy controls (P=0.0001 and 0.005 respectively). The serum levels of Vitamin D were also found to be lower in active TB group as compared to healthy controls (P =0.001). Levels of cathelicidin and NO was higher in patient group as compared to other groups (p=0.01 and 0.5 respectively). However, the expression of VDR and iNOS and levels of vitamin D was significantly (P < 0.05) higher in household contacts compared to both active TB and healthy control groups. Inference: Higher levels of Vitamin D along with VDR and iNOS expression in household contacts as compared to patients suggest that vitamin D might have a protective role against TB which prevents activation of the disease. From our data, we can conclude that decreased vitamin D levels could be implicated in disease progression and we can use cathelicidin and NO as a biomarker for early diagnosis of pulmonary tuberculosis.

Keywords: vitamin D, VDR, iNOS, tuberculosis

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Authors: Franco Miguel Nodado, Adrienne Marie Bugayong Janagap, Allen Claire Arances, Kirsten Anne Gerez, Frances Catherine Rosario, Charise Alvyne Samaniego, Matt Andrew Secular, Rommel Gestuveo, Marilyn Sumayo, Joseph Arbizo, Philip Ian Padilla

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COVID-19 pandemic adversely affected the delivery of health care services, but its impacts on Maternal, Newborn, Child Health and Nutrition (MNCHN) programs in rural municipalities in the Philippines remains understudied. Thus, this study explored the effects of the pandemic on MNCHN indicators in the municipalities of Miagao, Iloilo and Sibunag, Guimaras. A cross-sectional design was employed to compare the MNCHN indicators before and during the pandemic, and between Miagao and Sibunag. Key informant interviews (KII) were performed to identify the factors affecting access to MNCHN programs. During the pandemic, Miagao had a significant increase in positive outcomes of eight out of ten maternal health indicators, while Sibunag showed a significant decrease in six indicators. For child health and nutrition, Miagao obtained significant improvements in five of seven indicators, while Sibunag showed a significant increase in positive outcomes for six. KII data showed that the primary concern of mothers in Miagao is accessibility, while mothers in Sibunag raised concerns on accessibility, availability, and affordability of these MNCHN services. Miagao MHO employed various strategies such as telemedicine, activation of barangay health workers, and decentralization of health services to Barangay Health Centers, which can explain the improvements in MNCHN indicators. Sibunag also decentralized its health services, but its limited resources might have led them to prioritize child health and nutrition services. The findings suggest that the impacts of the COVID-19 pandemic on MNCHN depend on local health measures employed by the municipality, while telemedicine is a very useful tool in mitigating the negative effects of disrupted health services.

Keywords: maternal, child, COVID-19, Miagao, Sibunag, nutrition

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Authors: Javier Comes Fayos, Isabel Rodríguez Moreno, Sara Bressanutti, Marisol Lila, Angel Romero Martínez, Luis Moya Albiol

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Empathy is a cognitive-affective capacity whose deterioration is associated with aggressive behaviour. Deficient affective processing is one of the predominant risk factors in men convicted of intimate partner violence (IPV perpetrators), since it makes their capacity to empathize very difficult. The objective of this study is to compare the response of electrodermal activity (EDA), as an indicator of emotionality, to an empathic induction task, between IPV perpetrators and men without a history of violence. The sample was composed of 51 men who attended the CONTEXTO program, with penalties for gender violence under two years, and 47 men with no history of violence. Empathic induction was achieved through the visualization of 4 negative emotional-eliciting videos taken from an emotional induction battery of videos validated for the Spanish population. The participants were asked to actively empathize with the video characters (previously pointed out). The psychophysiological recording of the EDA was accomplished by the "Vrije Universiteit Ambulatory Monitoring System (VU-AMS)." An analysis of repeated measurements was carried out with 10 intra-subject measurements (time) and "group" (IPV perpetrators and non-violent perpetrators) as the inter-subject factor. First, there were no significant differences between groups in the baseline AED levels. Yet, a significant interaction between the “time” and “group” was found with IPV perpetrators exhibiting lower EDA response than controls after the empathic induction task. These findings provide evidence of a subdued EDA response after an empathic induction task in IPV perpetrators with respect to men without a history of violence. Therefore, the lower psychophysiological activation would be indicative of difficulties in the emotional processing and response, functions that are necessary for the empathic function. Consequently, the importance of addressing possible empathic difficulties in IPV perpetrator psycho-educational programs is reinforced, putting special emphasis on the affective dimension that could hinder the empathic function.

Keywords: electrodermal activity, emotional induction, empathy, intimate partner violence

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Authors: El-Said I. El-Shafey, Syeda Naheed F. Ali, Saleh S. Al-Busafi, Haider A. J. Al-Lawati

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Date palm leaflets were utilized as a precursor for activated carbon (AC) preparation using KOH activation. AC produced was oxidized using nitric acid producing oxidized activated carbon (OAC). OAC that possesses acidic surface was surface functionalized to produce basic activated carbons using linear diamine compounds (ethylene diamine and propylene diamine). OAC was also functionalized to produce hydrophobic activated carbons using ethylamine (EA) and aniline (AN). Dehydrated carbon was also prepared from date palm leaflets using sulfuric acid dehydration/ oxidation and was surface functionalized in the same way as AC. Nitric acid oxidation was not necessary for DC as it is acidic carbon. The surface area of AC is high (823 m2/g) with microporosity domination, however, after oxidation and surface functionalization, both the surface area and surface microporosity decrease tremendously. DC surface area was low (15 m2/g) with mesoporosity domination. Surface functionalization has decreased the surface area of activated carbons. FTIR spectra show that -COOH group on DC and OAC almost disappeared after surface functionalization. The surface chemistry of all carbons produced was tested for pHzpc, basic sites, boehm titration, thermogravimetric analysis and zeta potential measurement. Scanning electron microscopy and energy dispersive spectroscopy in addition to CHN elemental analysis were also carried out. DC and OAC possess low pHzpc and high surface functionality, however, basic and hydrophobic carbons possess high pHzpc and low surface functionality. The different behavior of carbons is related to their different surface chemistry. Methylene blue adsorption was found to be faster on hydrophobic carbons based on AC and DC. The Larger adsorption capacity of methylene blue was found for hydrophobic carbons. Dominating adsorption forces of methylene blue varies from carbon to another depending on its surface nature. Sorption forces include hydrophobic forces, H-bonding, electrostatic interactions and van der Waals forces.

Keywords: carbon, acidic, basic, hydrophobic

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Authors: Varun A Baheti, Sanjay Kashyap, Kamanio Chattopadhyay, Praveen Kumar, Aloke Paul

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Ni–Sn system finds applications in the microelectronics industry, especially with respect to flip–chip or direct chip, attach technology. Here the region of interest is under bump metallization (UBM), and solder bump (Sn) interface due to the formation of brittle intermetallic phases there. Understanding the growth of these phases at UBM/Sn interface is important, as in many cases it controls the electro–mechanical properties of the product. Cu and Ni are the commonly used UBM materials. Cu is used for good bonding because of fast reaction with solder and Ni often acts as a diffusion barrier layer due to its inherently slower reaction kinetics with Sn–based solders. Investigation on the growth kinetics of phases in Ni–Sn system is reported in this study. Just for simplicity, Sn being major solder constituent is chosen. Ni–Sn electroplated diffusion couples are prepared by electroplating pure Sn on Ni substrate. Bulk diffusion couples prepared by the conventional method are also studied along with Ni–Sn electroplated diffusion couples. Diffusion couples are annealed for 25–1000 h at 50–215°C to study the phase evolutions and growth kinetics of various phases. The interdiffusion zone was analysed using field emission gun equipped scanning electron microscope (FE–SEM) for imaging. Indexing of selected area diffraction (SAD) patterns obtained from transmission electron microscope (TEM) and composition measurements done in electron probe micro−analyser (FE–EPMA) confirms the presence of various product phases grown across the interdiffusion zone. Time-dependent experiments indicate diffusion controlled growth of the product phase. The estimated activation energy in the temperature range 125–215°C for parabolic growth constants (and hence integrated interdiffusion coefficients) of the Ni₃Sn₄ phase shed light on the growth mechanism of the phase; whether its grain boundary controlled or lattice controlled diffusion. The location of the Kirkendall marker plane indicates that the Ni₃Sn₄ phase grows mainly by diffusion of Sn in the binary Ni–Sn system.

Keywords: diffusion, equilibrium phase, metastable phase, the Ni-Sn system

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Authors: Da-Eun Kim, Heon-Seock Cynn, Sil-Ah Choi, A-Reum Shin

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Bridging exercise in supine position with the hips and knees flexed have been commonly performed as one of the therapeutic exercises and is a comfortable and pain-free position to most individuals with chronic low back pain (CLBP). Many previous studies have investigated the beneficial way of performing bridging exercises to improve activation of abdominal and gluteal muscle and reduce muscle activity of hamstrings (HAM) and erector spinae (ES) and compensatory lumbopelvic motion. The purpose of this study was to compare the effects of three different bridging exercises on the HAM, ES, gluteus maximus (Gmax), gluteus medius (Gmed), and transverse abdominis/internal abdominis oblique (TrA/IO) activities and anterior pelvic tilt angle in subjects with CLBP. Seventeen subjects with CLBP participated in this study. They performed bridging under three different conditions (with 30° hip abduction, isometric hip abduction, and isometric hip adduction). Surface electromyography was used to measure muscle activity, and the ImageJ software was used to calculate anterior pelvic tilt angle. One-way repeated-measures analysis of variance was used to assess the statistical significance of the measured variables. HAM activity was significantly lower in bridging with 30° hip abduction and isometric hip abduction than in bridging with isometric hip adduction. Gmax and Gmed activities were significantly greater in bridging with isometric hip abduction than in bridging with 30° hip abduction and isometric hip adduction. TrA/IO muscle activity was significantly greater and anterior pelvic tilt angle was significantly lower in bridging with isometric hip adduction than in bridging with 30° hip abduction and isometric hip abduction. Bridging with isometric hip abduction using Thera-Band can effectively reduce HAM activity, and increase Gmax and Gmed activities in subjects with CLBP. Bridging with isometric hip adduction using a pressure biofeedback unit can be a beneficial exercise to improve TrA/IO activity and minimize anterior pelvic tilt in subjects with CLBP.

Keywords: bridging exercise, electromyography, low back pain, lower limb exercise

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Authors: Yi Sun, George Ed Rainger, Steve P. Watson

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Background: Beyond the classical roles in haemostasis and thrombosis, platelets are important in the initiation and development of various thrombo-inflammatory diseases. In atherosclerosis and deep vein thrombosis, for example, platelets bridge monocytes with endothelium and form heterotypic aggregates with monocytes in the circulation. This can alter monocyte phenotype by inducing their activation, stimulating adhesion and migration. These interactions involve cell surface receptor-ligand pairs on both cells. This list is likely incomplete as new interactions of importance to platelet biology are continuing to be discovered as illustrated by our discovery of PEAR-1 binding to FcεR1α. Results: We have developed a highly sensitive avidity-based assay to identify novel extracellular interactions among 126 recombinantly-expressed platelet cell surface and secreted proteins involved in platelet aggregation. In this study, we will use this method to identify novel platelet-monocyte interactions. We aim to identify ligands for orphan receptors and novel partners of well-known proteins. Identified interactions will be studied in preliminary functional assays to demonstrate relevance to the inflammatory processes supporting atherogenesis. Conclusions: Platelet-monocyte interactions are essential for the development of thromboinflammatory disease. Up until relatively recently, technologies only allow us to limit our studies on each individual protein interaction at a single time. These studies propose for the first time to study the cell surface platelet-monocyte interactions in a systematic large-scale approach using a reliable screening method we have developed. If successful, this will likely to identify previously unknown ligands for important receptors that will be investigated in details and also provide a list of novel interactions for the field. This should stimulate studies on developing alternative therapeutic strategies to treat vascular inflammatory disorders such as atherosclerosis, DVT and sepsis and other clinically important inflammatory conditions.

Keywords: membrane proteins, large-scale screening, platelets, recombinant expression

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Authors: Rajapaksha Gedara Prasad Tharanga Jayasooriya, Matharage Gayani Dilshara, Yung Hyun Choi, Gi-Young Kim

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Camptothecin (CPT) is a quinolone alkaloid which inhibits DNA topoisomerase I that induces cytotoxicity in a variety of cancer cell lines. We previously showed that CPT effectively inhibited invasion of prostate cancer cells and also combined treatment with subtoxic doses of CPT and TNF-related apoptosis-inducing ligand (TRAIL) potentially enhanced apoptosis in a caspase-dependent manner in hepatoma cancer cells. Here, we found that treatment with CPT caused an irreversible cell cycle arrest in the G2/M phase. CPT-induced cell cycle arrest was associated with a decrease in protein levels of cell division cycle 25C (Cdc25C) and increased the level of cyclin B and p21. The CPT-induced decrease in Cdc25C was blocked in the presence of proteasome inhibitor MG132, thus reversed the cell cycle arrest. In addition to that treatment of CPT-increased phosphorylation of Cdc25C was the resulted of activation of checkpoint kinase 2 (Chk2), which was associated with phosphorylation of ataxia telangiectasia-mutated. Interestingly CPT induced G2/M phase of the cell cycle arrest is reactive oxygen species (ROS) dependent where ROS inhibitors NAC and GSH reversed the CPT-induced cell cycle arrest. These results further confirm by using transient knockdown of nuclear factor-erythroid 2-related factor 2 (Nrf2) since it regulates the production of ROS. Our data reveal that treatment of siNrf2 increased the ROS level as well as further increased the CPT induce G2/M phase cell cycle arrest. Our data also indicate CPT-enhanced cell cycle arrest through the extracellular signal-regulated kinase (ERK) and the c-Jun N-terminal kinase (JNK) pathway. Inhibitors of ERK and JNK more decreased the Cdc25C expression and protein expression of p21 and cyclin B. These findings indicate that Chk2-mediated phosphorylation of Cdc25C plays a major role in G2/M arrest by CPT.

Keywords: camptothecin, cell cycle, checkpoint kinase 2, nuclear factor-erythroid 2-related factor 2, reactive oxygen species

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Authors: P. Y. Chiang, Y. H. Chen, Y. J. Lin, C. C. Chang, W. C. Hsu

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The number of the elderly in the world population and the rate of falls in this increasing numbers of older people are increasing. Decreasing muscle strength and an increasing risk of falling are associated with the ageing process. Because the effects of seated stepping training on the walking performance in the elderly remain unclear, the main purpose of the proposed study is to perform electromyography analysis during walking and seated stepping in the elderly. Four surface EMG electrodes were sticked on the surface of lower limbs muscles, including vastus lateralis (VL), and gastrocnemius (GT) of both sides. Before test, maximal voluntary contraction (MVC) of the respective muscle was obtained using manual muscle testing. The analog raw data of EMG signals were digitized with a sampling frequency of 2000 Hz. The signals were fully rectified and the linear envelope were calculated. Stepping motion cycle was separated into two phases by stepping timing (ST) and pedal return timing (PRT). ST refer to the time when the pedal marker reached the highest height, representing the contra-lateral leg was going to release the pedal. PRT refer to the time when the pedal marker reached the lowest height, representing the contra-lateral leg was going to step the pedal. We assumed that ST acted the same role in initial contact during walking, and PRT for toe-off. The period from ST to next PRT was called pushing phase (PP), during which the leg would start to step with resistance, and we compare this phase with the stance phase in level walking. The period from PRT to next ST was called returning phase (RP), during which leg would not have any resistance in this phase, and we compare this phase with the swing phase in level walking. VL and Gastro muscular activation had similar patterns in both side. The ability may transfer to those needed during loading response, mid-stance and terminal swing phase. User needed to make more effort in stepping compared with walking with similar timing; thus the strengthening of the VL and Gastro may be helpful to improve the walking endurance and efficiency for the elderly.

Keywords: elderly, electromyography, seated stepping, walking

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Authors: Camellia Al-Ibrahim, Jenny Yiend, Sukhwinder S. Shergill

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Background: Attention bias to threat play a role in the development, maintenance, and exacerbation of delusional beliefs in schizophrenia in which patients emphasize the threatening characteristics of stimuli and prioritise them for processing. Cognitive control deficits arise when task-irrelevant emotional information elicits attentional bias and obstruct optimal performance. This study is investigating neural correlates of interference effect of linguistic threat and whether these effects are independent of delusional severity. Methods: Using an event-related functional magnetic resonance imaging (fMRI), neural correlates of interference effect of linguistic threat during the emotional Stroop task were investigated and compared patients with schizophrenia with high (N=17) and low (N=16) paranoid symptoms and healthy controls (N=20). Participants were instructed to identify the font colour of each word presented on the screen as quickly and accurately as possible. Stimuli types vary between threat-relevant, positive and neutral words. Results: Group differences in whole brain effects indicate decreased amygdala activity in patients with high paranoid symptoms compared with low paranoid patients and healthy controls. Regions of interest analysis (ROI) validated our results within the amygdala and investigated changes within the striatum showing a pattern of reduced activation within the clinical group compared to healthy controls. Delusional severity was associated with significant decreased neural activity in the striatum within the clinical group. Conclusion: Our findings suggest that the emotional interference mediated by the amygdala and striatum may reduce responsiveness to threat-related stimuli in schizophrenia and that attenuation of fMRI Blood-oxygen-level dependent (BOLD) signal within these areas might be influenced by the severity of delusional symptoms.

Keywords: attention bias, fMRI, Schizophrenia, Stroop

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Authors: Pavel Borodkin, Nikolay Khrennikov, Azamat Gazetdinov

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The problem of ensuring of VVER type reactor equipment integrity is now most actual in connection with justification of safety of the NPP Units and extension of their service life to 60 years and more. First of all, it concerns old units with VVER-440 and VVER-1000. The justification of the VVER equipment integrity depends on the reliability of estimation of the degree of the equipment damage. One of the mandatory requirements, providing the reliability of such estimation, and also evaluation of VVER equipment lifetime, is the monitoring of equipment radiation loading parameters. In this connection, there is a problem of justification of such normative parameters, used for an estimation of the pressure vessel metal embrittlement, as the fluence and fluence rate (FR) of fast neutrons above 0.5 MeV. From the point of view of regulatory practice, a comparison of displacement per atom (DPA) and fast neutron fluence (FNF) above 0.5 MeV has a practical concern. In accordance with the Russian regulatory rules, neutron fluence F(E > 0.5 MeV) is a radiation exposure parameter used in steel embrittlement prediction under neutron irradiation. However, the DPA parameter is a more physically legitimate quantity of neutron damage of Fe based materials. If DPA distribution in reactor structures is more conservative as neutron fluence, this case should attract the attention of the regulatory authority. The purpose of this work was to show what radiation load parameters (fluence, DPA) on all VVER equipment should be under control, and give the reasonable estimations of such parameters in the volume of all equipment. The second task is to give the conservative estimation of each parameter including its uncertainty. Results of recently received investigations allow to test the conservatism of calculational predictions, and, as it has been shown in the paper, combination of ex-vessel measured data with calculated ones allows to assess unpredicted uncertainties which are results of specific unique features of individual equipment for VVER reactor. Some results of calculational-experimental investigations are presented in this paper.

Keywords: equipment integrity, fluence, displacement per atom, nuclear power plant, neutron activation measurements, neutron transport calculations

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Authors: S. Y. Park, S. M. Lee, S. H. Lee, K. M. Lim

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In this research analyzed the effects that phase formation reaction change in the grey cast iron makes on characteristics of microstructures, liquidity, and mechanical properties through cooling curve when adding rare earth elements (R.E). This research was analyzed with comparison between the case of not adding the rare earth elements (R.E) into the grey cast iron with the standard composition (as 3.3%C-2.1%Si-0.7%Mn-0.1%S) and the case of adding 0.3% rare earth elements (R.E). The thermal analysis parameters have been drawn through eutectic temperature theoretically calculated, recalescence temperature, and undercooling temperature measured from start of eutectic reaction to end of solidification in the cooling curve obtained by thermal analysis to analyze formation behavior of graphite, and the effects by addition of rare earth elements on this have been reviewed. When adding rare earth elements (R.E), the cause of liquidity slowdown was analyzed trough the solidification starting temperature and change of solidification ending temperature. The strength and hardness have been measured to evaluate the mechanical properties, and the sound tensile strength has been evaluated through quality coefficient after measuring relative hardness and normality degree of tensile strength by calculating theoretical tensile strength and theoretical hardness. The change of Pearlite Inter-lamellar Spacing of matrix microstructure and eutectic cell count of macrostructure was measured to analyze the effects of the rare earth elements on the sound tensile strength. The change of eutectic cell count has been clarified through activation of the eutectic reaction, and the cause of pearlite inter-lamellar spacing clarified through eutectoid reaction temperature.

Keywords: cooling curve, element, grey cast iron, thermal analysis, rare earth element

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Authors: Chante J. De Klerk

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The potential of music to facilitate superior performance during high to elite level gymnastics conditioning instigated this research. A team of seven gymnasts completed a fixed conditioning programme eight times, alternating the two variable conditions. Four sessions of each condition were conducted: without music (session 1), with music (session 2), without music (3), with music (4), without music (5), and so forth. Quantitative data were collected in both conditions through physiological monitoring of the gymnasts, and administration of the Situational Motivation Scale (SIMS). Statistical analysis of the physiological data made it possible to quantify the presence as well as the magnitude of the musical intervention’s impact on various aspects of the gymnasts' physiological functioning during conditioning. The SIMS questionnaire results were used to evaluate if their motivation towards conditioning was altered by the intervention. Thematic analysis of qualitative data collected through semi-structured interviews revealed themes reflecting the gymnasts’ sentiments towards the data collection process. Gymnast-specific descriptions and experiences of the team as a whole were integrated with the quantitative data to facilitate greater dimension in establishing the impact of the intervention. The results showed positive physiological, motivational, and emotional effects. In the presence of music, superior sympathetic nervous activation, and energy efficiency, with more economic breathing, dominated the physiological data. Fatigue and arousal levels (emotional and physiological) were also conducive to improved conditioning outcomes compared to conventional conditioning (without music). Greater levels of positive affect and motivation emerged in analysis of both the SIMS and interview data sets. Overall, the intervention was found to promote psychophysiological coherence during the physical activity. In conclusion, a strategically constructed musical intervention, designed to accompany a gymnastics conditioning session for high to elite level gymnasts, has ergogenic potential.

Keywords: arousal, fatigue, gymnastics conditioning, motivation, musical intervention, psychophysiological coherence

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Authors: L. Marcos Domínguez, Nils Rage, Ongun B. Kazanci, Bjarne W. Olesen

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Thermally Activated Building Systems (TABS) have proven to be an energy-efficient solution to provide buildings with an optimal indoor thermal environment. This solution uses the structure of the building to store heat, reduce the peak loads, and decrease the primary energy demand. TABS require the heated or cooled surfaces to be as exposed as possible to the indoor space, but exposing the bare concrete surfaces has a diminishing effect on the acoustic qualities of the spaces in a building. Acoustic solutions capable of providing optimal acoustic comfort and allowing the heat exchange between the TABS and the room are desirable. In this study, the effects of free-hanging units on the cooling performance of TABS and the occupants’ thermal comfort was measured in a full-scale TABS laboratory. Investigations demonstrate that the use of free-hanging sound absorbers are compatible with the performance of TABS and the occupant’s thermal comfort, but an appropriate acoustic design is needed to find the most suitable solution for each case. The results show a reduction of 11% of the cooling performance of the TABS when 43% of the ceiling area is covered with free-hanging horizontal sound absorbers, of 23% for 60% ceiling coverage ratio and of 36% for 80% coverage. Measurements in actual buildings showed an increase of the room operative temperature of 0.3 K when 50% of the ceiling surface is covered with horizontal panels and of 0.8 to 1 K for a 70% coverage ratio. According to numerical simulations using a new TRNSYS Type, the use of comfort ventilation has a considerable influence on the thermal conditions in the room; if the ventilation is removed, then the operative temperature increases by 1.8 K for a 60%-covered ceiling.

Keywords: acoustic comfort, concrete core activation, full-scale measurements, thermally activated building systems, TRNSys

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Authors: Ji-Young Choi, Jungjin Kim, Sang-Sun Yun, Sangmee Ahn Jo

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Intracellular adhesion molecule1 (ICAM1) is a mediator of inflammation and involved in adhesion and transmigration of leukocytes to endothelial cells, resulting in enhancement of brain inflammation. We hypothesized that increase of ICAM1 expression in endothelial cells is an early step in the pathogenesis of brain diseases such as Alzheimer’s disease. Here, we report that ICAM1 expression is regulated by pro-inflammatory cytokine TNFa in human microvascular endothelial cell (HBMVEC). TNFa significantly increased ICAM1 mRNA and protein levels at the concentrations showing no cell toxicity. This increase was also shown in micro vessels of mouse brain 24 hours after treatment with TNFa (8 mg/kg, i.v). We then investigated the epigenetic mechanism involved in the induction of ICAM1 expression. Chromatin immunoprecipitation assay revealed that TNFa reduced methylation of histone3K9 (H3K9-2me) and histone3K27 (H3K27-3me), well-known modification as gene suppression, with in the ICAM1 promoter region. However, acetylation of H3K9 and H3K14, well-known modification as gene activation, was not changed by TNFa. Treatment of BIX01294, a specific inhibitor of histone methyltransferase G9a responsible for H3K9-2me, dramatically increased in ICAM1 mRNA and protein levels and overexpression of G9a gene suppressed TNFa-induced ICAM1 expression. In contrast, GSK126, an inhibitor of histone methyltransferase EZH2 responsible for H3K27-3me and valproic acid, an inhibitor of histone deacetylase (HDAC) did not affect ICAM1 expression. These results suggested that histone3 methylation is involved in ICAM1 repression. Moreover, TNFa or BIX01294-induced ICAM induction resulted in both enhancements in adhesion and transmigration of leukocyte on endothelial cell. This study demonstrates that TNFa upregulates ICAM1 expression through H3K9-2me and H3K27-3me within the ICAM1 promoter region, in which G9a is likely to play a pivotal role in ICAM1 transcription. Our study provides a novel mechanism for ICAM1 transcription regulation in HBMVEC.

Keywords: ICAM1, TNFa, HBMVEC, H3K9-2me

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Authors: Yori Gidron, Laura Caton, Irit Ben-Aharon

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Background: Many patients and even certain clinicians attribute cancer development to psychosocial factors. Yet, empirical data supports more the prognostic role, rather than the etiological role, of psychosocial factors in cancer. Part of the inconsistency may result from not considering possible moderating factors in the etiological role of psychosocial factors. One important candidate moderating factor is the vagal nerve, whose activity is indexed by heart-rate variability (HRV). The vagal nerve may prevent cancer since it reduces inflammation on the one hand, and since it increases anti-tumor immunity on the other hand. This study examined the moderating role of the vagus in the relation between life threatening events (LTE) and cancer development. Method: We re-analyzed data from the Lifelines Dutch longitudinal cohort study of over 150,000 people. The present study included 82,751 adults, who initially were cancer-free. We extracted information on background factors (e.g., age, gender, fat consumption), whether they ever experienced LTE, HRV and cancer diagnosis as reported by patients in annual clinic visits. HRV was derived from brief ECGs. Results: Of the full sample, 1011 people developed cancer during a follow-up. In the full sample, LTE significantly predicted cancer development (R.R = 1.063 p < .01) and HRV significantly predicted a reduced risk of cancer development (R.R = .506 p <.001). Importantly, LTE significantly predicted cancer only when HRV was low (R.R = 1.056, 95% CI: 1.007 - 1.108, p < .05) but not when HRV was high (R.R = 1.014; 95% CI: 0.916 - 1.122, p > 0.05), independent of confounders. Conclusions: To the best of our knowledge, this is the first study showing in a large sample that LTE predict cancer development, and that this occurs only when vagal nerve activity (HRV) is relatively low. These results could result from lack of vagal modulation of inflammation and also from lack of vagal modulation of stress responses. Results are in line with the cancer-protective role of the vagus. HRV needs to be routinely monitored in the population and future intervention trials need to examine whether vagal nerve activation can prevent cancer in people with LTE and with other cancer risk factors.

Keywords: cancer development, life-events, moderation, vagal nerve

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Authors: Shrawan Baghel, Helen Cathcart, Biall J. O'Reilly

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Amorphous drug formulations have great potential to enhance solubility and thus bioavailability of BCS class II drugs. However, the higher free energy and molecular mobility of the amorphous form lowers the activation energy barrier for crystallization and thermodynamically drives it towards the crystalline state which makes them unstable. Accurate determination of the crystallization tendency/kinetics is the key to the successful design and development of such systems. In this study, dipyridamole (DPM) and cinnarizine (CNZ) has been selected as model compounds. Thermodynamic fragility (m_T) is measured from the heat capacity change at the glass transition temperature (Tg) whereas dynamic fragility (m_D) is evaluated using methods based on extrapolation of configurational entropy to zero 〖(m〗_(D_CE )), and heating rate dependence of Tg 〖(m〗_(D_Tg)). The mean relaxation time of amorphous drugs was calculated from Vogel-Tammann-Fulcher (VTF) equation. Furthermore, the correlation between fragility and glass forming ability (GFA) of model drugs has been established and the relevance of these parameters to crystallization of amorphous drugs is also assessed. Moreover, the crystallization kinetics of model drugs under isothermal conditions has been studied using Johnson-Mehl-Avrami (JMA) approach to determine the Avrami constant ‘n’ which provides an insight into the mechanism of crystallization. To further probe into the crystallization mechanism, the non-isothermal crystallization kinetics of model systems was also analysed by statistically fitting the crystallization data to 15 different kinetic models and the relevance of model-free kinetic approach has been established. In addition, the crystallization mechanism for DPM and CNZ at each extent of transformation has been predicted. The calculated fragility, glass forming ability (GFA) and crystallization kinetics is found to be in good correlation with the stability prediction of amorphous solid dispersions. Thus, this research work involves a multidisciplinary approach to establish fragility, GFA and crystallization kinetics as stability predictors for amorphous drug formulations.

Keywords: amorphous, fragility, glass forming ability, molecular mobility, mean relaxation time, crystallization kinetics, stability

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Authors: Afsaneh Mohammadnejad, Marianne Nygaard, Jan Baumbach, Shuxia Li, Weilong Li, Jesper Lund, Jacob v. B. Hjelmborg, Lene Christensen, Qihua Tan

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Cognitive impairment in the elderly is a key issue affecting the quality of life. Despite a strong genetic background in cognition, only a limited number of single nucleotide polymorphisms (SNPs) have been found. These explain a small proportion of the genetic component of cognitive function, thus leaving a large proportion unaccounted for. We hypothesize that one reason for this missing heritability is the misspecified modeling in data analysis concerning phenotype distribution as well as the relationship between SNP dosage and the phenotype of interest. In an attempt to overcome these issues, we introduced a model-free method based on the generalized correlation coefficient (GCC) in a genome-wide association study (GWAS) of cognitive function in twin samples and compared its performance with two popular linear regression models. The GCC-based GWAS identified two genome-wide significant (P-value < 5e-8) SNPs; rs2904650 near ZDHHC2 on chromosome 8 and rs111256489 near CD6 on chromosome 11. The kinship model also detected two genome-wide significant SNPs, rs112169253 on chromosome 4 and rs17417920 on chromosome 7, whereas no genome-wide significant SNPs were found by the linear mixed model (LME). Compared to the linear models, more meaningful biological pathways like GABA receptor activation, ion channel transport, neuroactive ligand-receptor interaction, and the renin-angiotensin system were found to be enriched by SNPs from GCC. The GCC model outperformed the linear regression models by identifying more genome-wide significant genetic variants and more meaningful biological pathways related to cognitive function. Moreover, GCC-based GWAS was robust in handling genetically related twin samples, which is an important feature in handling genetic confounding in association studies.

Keywords: cognition, generalized correlation coefficient, GWAS, twins

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Authors: Aliya Sekenova, Vyacheslav Ogay

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The derivation of human induced pluripotent stem cells (iPSCs) from somatic cells by direct reprogramming opens wide perspectives in the regenerative medicine. It means the possibility to develop the personal and, consequently, any immunologically compatible cells for applications in cell-based therapy. The purpose of our study was to develop the technology for the production of NK cells from T cell-derived induced pluripotent stem cells (TiPSCs) for subsequent application in adoptive cancer immunotherapy. Methods: In this study iPSCs were derived from peripheral blood T cells using Sendai virus vectors expressing Oct4, Sox2, Klf4 and c-Myc. Pluripotent characteristics of TiPSCs were examined and confirmed with alkaline phosphatase staining, immunocytochemistry and RT-PCR analysis. For NK cell differentiation, embryoid bodies (EB) formed from (TiPSCs) were cultured in xenogeneic serum-free medium containing human serum, IL-3, IL-7, IL-15, SCF, FLT3L without using M210-B4 and AFT-024 stromal feeder cells. After differentiation, NK cells were characterized with immunofluorescence analysis, flow cytometry and cytotoxicity assay. Results: Here, we for the first time demonstrate that TiPSCs can effectively differentiate into functionally active NK cells without M210-B4 and AFT-024 xenogeneic stroma cells. Immunofluorescence and flow cytometry analysis showed that EB-derived cells can differentiate into a homogeneous population of NK cell expressing high levels of CD56, CD45 and CD16 specific markers. Moreover, these cells significantly express killing activation receptors such as NKp44 and NKp46. In the comparative analysis, we observed that NK cells derived using feeder-free culture system have more high killing activity against K-562 tumor cells, than NK cells derived by feeder-dependent method. Thus, we think that our obtained data will be useful for the development of large-scale production of NK cells for translation into cancer immunotherapy.

Keywords: induced pluripotent stem cells, NK cells, T cells, cell diffentiation, feeder cell-free culture system

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Authors: Gerhardt Boukes, Maryna Van De Venter, Sharlene Govender

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Macrofungi have been used for the past two thousand years in Asian countries, and more recently in Western countries, for their medicinal properties. Biological activities include antimicrobial, antioxidant, anti-inflammatory, antidiabetic, anticancer and immunomodulatory to name a few. Several biologically active compounds have been identified and isolated. Macrofungal research in Africa is poorly documented and to the best of our knowledge non-existent. South Africa has a rich macrofungal biodiversity, which includes endemic and exotic macrofungal species. Ethanolic extracts of 13 macrofungal species, including mushrooms, bracket fungi and puffballs, were prepared and screened for cytotoxicity against a panel of seven cell lines, including A549 (human lung adenocarcinoma), HeLa (human cervical adenocarcinoma), HT-29 (human colorectal adenocarcinoma), MCF7 (human breast adenocarcinoma), MIA PaCa-2 (human pancreatic ductal adenocarcinoma), PC-3 (human prostate adenocarcinoma) and Vero (African green monkey kidney epithelial) cells using MTT. Cell lines were chosen according to the most prevalent cancer types affecting males and females in South Africa and globally, and the mutations they contain. Preliminary results have shown that three of the macrofungal genera, i.e. Fomitopsis, Gymnopilus and Pycnoporus, have shown cytotoxic activity, ranging between IC50 ~20 and 200 µg/mL. The molecular mechanism of action contributing to cell death investigated and being investigated include apoptosis (i.e. DNA cell cycle arrest, caspase-3 activation and mitochondrial membrane potential), autophagy (i.e. acridine orange and LC3B staining) and ER stress (i.e. thioflavin T staining and caspase-12) in the presence of melphalan, chloroquine and thapsigargin/tuncamycin as positive controls, respectively. The genus, Pycnoporus, has shown the best cytotoxicity of the three macrofungal genera. Future work will focus on the identification and isolation of novel active compounds and elucidating the mechanism/s of action.

Keywords: cancer, cytotoxicity, macrofungi, mechanism/s of action

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