Search results for: regional expression

Authors: Zhipeng Yan, Janice Wing-Tung Kwong, Ching-Lung Lai

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Background: Advanced melanoma accounts for the majority of skin cancer death due to its poor prognosis. Nivolumab and ipilimumab are monoclonal antibodies targeting programmed cell death protein 1 (PD-1) and cytotoxic T-lymphocytes antigen 4 (CTLA-4). Nivolumab and ipilimumab combination therapy has been proven to be effective for advanced melanoma. This systematic review and meta-analysis are to evaluate its clinical efficacy and adverse events. Method: A systematic search was done on databases (Pubmed, Embase, Medline, Cochrane) on 21 June 2020. Search keywords were nivolumab, ipilimumab, melanoma, and randomised controlled trials. Clinical trials fulfilling the inclusion criteria were selected to evaluate the efficacy of combination therapy in terms of prolongation of progression-free survival (PFS), overall survival (OS), and objective response rate (ORR). The odd ratios and distributions of grade 3 or above adverse events were documented. Subgroup analysis was performed based on PD-L1 expression-status and BRAF-mutation status. Results: Compared with nivolumab monotherapy, the hazard ratios of PFS, OS and odd ratio of ORR in combination therapy were 0.64 (95% CI, 0.48-0.85; p=0.002), 0.84 (95% CI, 0.74-0.95; p=0.007) and 1.76 (95% CI, 1.51-2.06; p < 0.001), respectively. Compared with ipilimumab monotherapy, the hazard ratios of PFS, OS and odd ratio of ORR were 0.46 (95% CI, 0.37-0.57; p < 0.001), 0.54 (95% CI, 0.48-0.61; p < 0.001) and 6.18 (95% CI, 5.19-7.36; p < 0.001), respectively. In combination therapy, the odds ratios of grade 3 or above adverse events were 4.71 (95% CI, 3.57-6.22; p < 0.001) compared with nivolumab monotherapy, and 3.44 (95% CI, 2.49-4.74; p < 0.001) compared with ipilimumab monotherapy, respectively. High PD-L1 expression level and BRAF mutation were associated with better clinical outcomes in patients receiving combination therapy. Conclusion: Combination therapy is effective for the treatment of advanced melanoma. Adverse events were common but manageable. Better clinical outcomes were observed in patients with high PD-L1 expression levels and positive BRAF-mutation.

Keywords: nivolumab, ipilimumab, advanced melanoma, systematic review, meta-analysis

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Authors: Maysam Mard-Soltani, Mohamad Javad Rasaee, Saeed Khalili, Abdol Karim Sheikhi, Mehdi Hedayati

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Production of specific antibody responses against hTSH is a cumbersome process due to the high identity between the hTSH and the other members of the glycoprotein hormone family (FSH, LH and HCG) and the high identity between the human hTSH and host animals for antibody production. Therefore, two polyclonal antibodies were purified against two recombinant proteins. Four possible ELISA tests were designed based on these antibodies. These ELISA tests were checked against hTSH and other glycoprotein hormones, and their sensitivity and specificity were assessed. Bioinformatics tools were used to analyze the immunological properties. After the immunogen region selection from hTSH protein, c terminal of B hTSH was selected and applied. Two recombinant genes, with these cut pieces (first: two repeats of C terminal of B hTSH, second: tetanous toxin+B hTSH C terminal), were designed and sub-cloned into the pET32a expression vector. Standard methods were used for protein expression, purification, and verification. Thereafter, immunizations of the white New Zealand rabbits were performed and the serums of them were used for antibody titration, purification and characterization. Then, four ELISA tests based on two antibodies were employed to assess the hTSH and other glycoprotein hormones. The results of these assessments were compared with standard amounts. The obtained results indicated that the desired antigens were successfully designed, sub-cloned, expressed, confirmed and used for in vivo immunization. The raised antibodies were capable of specific and sensitive hTSH detection, while the cross reactivity with the other members of the glycoprotein hormone family was minimum. Among the four designed tests, the test in which the antibody against first protein was used as capture antibody, and the antibody against second protein was used as detector antibody did not show any hook effect up to 50 miu/l. Both proteins have the ability to induce highly sensitive and specific antibody responses against the hTSH. One of the antibody combinations of these antibodies has the highest sensitivity and specificity in hTSH detection.

Keywords: hTSH, bioinformatics, protein expression, cross reactivity

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Authors: Ebru Thwaites Diken

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This article analyzes the works of certain directors in Danish cinema, namely Susanne Bier and Lone Sherfig, in the context of transnationalisation of Danish cinema. It looks at how the films' narratives negotiate and reconstruct the local / national / regional and the global. Scholars such as Nestingen & Elkington (2005), Hjort (2010), Higbee and Lim (2010), Bondebjerg and Redvall (2011) address transnationalism of Danish cinema in terms of production and distribution processes and how film making trascends national boundaries. This paper employs a particular understanding of transnationalism - in terms of how ideas and characters travel - to analyze how the storytelling and style has evolved to connect the national, the regional and the global on the basis of the works of these two directors. Strategies such as Hollywoodization - i.e. focus on stardom and classical narration, adhering to conventional European genre formulas, producing Danish films in English language have been identifiable strategies in Danish cinema in the period after the 2000s. Susanne Bier and Lone Scherfig are significant for employing some of these strategies simultaneously. For this reason, this article will look at how these two directors have employed these strategies and negotiated the cultural boundaries and exchanges.

Keywords: transnational cinema, danish cinema, susanne bier, lone scherfig

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Authors: Xing Wang, Lin Feng, Lingling E., Hongchen Liu

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In patients with type 2 diabetes mellitus (DM) there is poorer quality osseointegration than in non-diabetic (n-DM) patients, and the success of dental implants is less. Recent studies have demonstrated that insulin could stimulate bone cells to produce and accelerate implant osseointegration in DM patients.This raised the question whether insulin could provide local bone anabolic effects in non-diabetic patients. In this study,48 SD rats were divided into four groups randomly: DM group, DM+insulin group, n-DM group, n-DM + insulin group. All rats were implanted the titanium implant near the epiphyseal end of tibia, then the DM + insulin and n-DM + insulin group received twice-daily subcutaneous injections of insulin (10U/day).Two,four and eight weeks after implantation, rats were killed in batches. Histomorphometry and immunohistochemistry were used to evaluate bone formation and osseointegration. The amount of newly formed bone, Implant–bone contact and the expression of OCN,RUNX2 in the DM+insulin, n-DM and n-DM+insulin group were significantly more than in the DM group (p<0.05). Compared with the n-DM group,the Implant–bone contact and expression of OCN,RUNX2 were significantly increased in n-DM+insulin group (p< 0.05). Taken together,these observations provide evidence that insulin has the potential to increase bone formation and osseointegration around implant not only in diabetic subjects but also in non-diabetic subject.

Keywords: insulin, diabetes mellitus, osseointegration, dental implants

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Authors: Sylvia Szabo, Thilini Navaratne, Indrajit Pal, Seree Park

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Deltaic and coastal regions are often strategically important both from local and regional perspectives. While deltas are known to be bread baskets of the world, delta inhabitants often face the risk of food and nutritional insecurity. These risks are highly exacerbated by the impacts of climate and environmental change. While numerous regional studies examined the prevalence and the determinants of food security in specific delta and coastal regions, there is still a lack of a systematic analysis of the most widely used scientific food security indicators. In order to fill this gap, a systematic review was carried out using Covidence, a Cochrane-adopted systematic review processing software. Papers included in the review were selected from the SCOPUS, Thomson Reuters Web of Science, Science Direct, ProQuest, and Google Scholar databases. Both scientific papers and grey literature (e.g., reports by international organizations) were considered. The results were analyzed by food security components (access, availability, quality, and strategy) and by world regions. Suggestions for further food security, nutrition, and health research, as well as policy-related implications, are also discussed.

Keywords: delta regions, coastal, food security, indicators, systematic review

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Authors: Yu-Hsin Tsai

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A new, mandated county regional plan system has been initiated since 2010 nationwide in Taiwan, with its role situated in-between the policy-led cross-county regional plan and the blueprint-led city plan. This new regional plan contain both urban and rural areas in one single plan, which provides a more complete planning territory, i.e., city region within the county’s jurisdiction, and to be executed and managed effectively by the county government. However, the full picture of its functions and characteristics seems still not totally clear, compared with other levels of plans; either are planning goals and issues that can be most appropriately dealt with at this spatial scale. In addition, the extent to which the inclusion of sustainability ideal and measures to cope with climate change are unclear. Based on the above issues, this study aims to clarify the roles of county regional plan, to analyze the extent to which the measures cope with sustainability, climate change, and forecasted declining population, and the success factors and issues faced in the planning process. The methodology applied includes literature review, plan quality evaluation, and interview with officials of the central and local governments and urban planners involved for all the 23 counties in Taiwan. The preliminary research results show, first, growth management related policies have been widely implemented and expected to have effective impact, including incorporating resources capacity to determine maximum population for the city region as a whole, developing overall vision of urban growth boundary for all the whole city region, prioritizing infill development, and use of architectural land within urbanized area over rural area to cope with urban growth. Secondly, planning-oriented zoning is adopted in urban areas, while demand-oriented planning permission is applied in the rural areas with designated plans. Then, public participation has been evolved to the next level to oversee all of government’s planning and review processes due to the decreasing trust in the government, and development of public forum on the internet etc. Next, fertile agricultural land is preserved to maintain food self-supplied goal for national security concern. More adoption-based methods than mitigation-based methods have been applied to cope with global climate change. Finally, better land use and transportation planning in terms of avoiding developing rail transit stations and corridor in rural area is promoted. Even though many promising, prompt measures have been adopted, however, challenges exist to surround: first, overall urban density, likely affecting success of UGB, or use of rural agricultural land, has not been incorporated, possibly due to implementation difficulties. Second, land-use related measures to mitigating climate change seem less clear and hence less employed. Smart decline has not drawn enough attention to cope with predicted population decrease in the next decade. Then, some reluctance from county’s government to implement county regional plan can be observed vaguely possibly since limits have be set on further development on agricultural land and sensitive areas. Finally, resolving issue on existing illegal factories on agricultural land remains the most challenging dilemma.

Keywords: city region plan, sustainability, global climate change, growth management

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Authors: H. K. Ratre, M. Roy, S. Roy, M. S. Parmar, V. Bhagat

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Mastitis is a common problem of dairy industries. Reduction in milk production and an irreparable damage to the udder associated with the disease are common causes of culling of dairy cows. Milk from infected animals is not suitable for drinking and for making different milk products. So, it has a major economic importance in dairy cattle. The aims of this study were to investigate the bacteriological panorama in milk from udder quarters with subclinical mastitis and to carried out for the molecular characterization of the major isolated organisms, from subclinical mastitis-affected cows in and around Durg and Rajnandgaon district of Chhattisgarh. Isolation and identification of bacteria from the milk samples of subclinical mastitis-affected cows were done by standard and routine culture procedures. A total of 78 isolates were obtained from cows and among the various bacteria isolated, Staphylococcus spp. occupied prime position with occurrence rate of 51.282%. However, other bacteria isolated includeStreptococcus spp. (20.512%), Micrococcus spp. (14.102%), E. coli (8.974%), Klebsiela spp. (2.564%), Salmonella spp. (1.282%) and Proteus spp. (1.282%). Staphylococcus spp. was isolated as the major causative agent of subclinical mastitis in the studied area. Molecular characterization of Staphylococus aureusisolates was done for genetic expression of the virulence genes like ‘nuc’ encoding thermonucleaseexoenzyme, coa and spa by PCR amplification of the respective genes in 25 Staphylococcus isolates. In the present study, 15 isolates (77.27%) out of 20 coagulase positive isolates were found to be genotypically positive for ‘nuc’ where as 20 isolates (52.63%) out of 38 CNS expressed the presence of the same virulence gene. In the present study, three Staphylococcus isolates were found to be genotypically positive for coa gene. The Amplification of the coa gene yielded two different products of 627, 710 bp. The amplification of the gene segment encoding the IgG binding region of protein A (spa) revealed a size of 220 and 253bp in twostaphylococcus isolates. The X-region binding of the spa gene produced an amplicon of 315 bp in one Staphylococcal isolates. Staphylococcus aureus was found to be major isolate (51.28%) responsible for causing subclinical mastitis in cows which also showed expression of virulence genesnuc, coa and spa.

Keywords: mastitis, bacteria, characterization, expression, gene

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Authors: Muna Shafiq

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Growth in international immigration is a reflection of increased migration patterns in Canada and in other parts of the world. Canada continues to promote itself as a bilingual country, yet the bilingual French and English population numbers do not reflect this platform. Each province’s integration policies focus only on second language learning of either English or French. Moreover, since English Canadians outnumber French Canadians, maintaining, much less increasing, English-French bilingualism appears unrealistic. One solution to increasing Canadian bilingualism requires creating intercultural communication initiatives between youth in Quebec and the rest of Canada. Specifically, the focus is on active, experiential learning, where intercultural competencies develop outside traditional classroom settings. The target groups are Generation Y Millennials and Generation Z Linksters, the next generations in the career and parenthood lines. Today, Canada’s education system, like many others, must continually renegotiate lines between programs it offers its immigrant and native communities. While some purists or right-wing nationalists would disagree, the survival of bilingualism in Canada has little to do with reducing immigration. Children and youth immigrants play a valuable role in increasing Canada’s French and English speaking communities. For instance, a focus on more immersion, over core French education programs for immigrant children and youth would not only increase bilingual rates; it would develop meaningful intercultural attachments between Canadians. Moreover, a vigilant increase of funding in French immersion programs is critical, as are new initiatives that focus on experiential language learning for students in French and English language programs. A favorable argument supports the premise that other than French-speaking students in Québec and elsewhere in Canada, second and third generation immigrant students are excellent ambassadors to promote bilingualism in Canada. Most already speak another language at home and understand the value of speaking more than one language in their adopted communities. Their dialogue and participation in experiential language exchange workshops are necessary. If the proposed exchanges take place inter-provincially, the momentum to increase collective regional voices increases. This regional collectivity can unite Canadians differently than nation-targeted initiatives. The results from an experiential youth exchange organized in 2017 between students at the crossroads of Generation Y and Generation Z in Vancouver and Quebec City respectively offer a promising starting point in assessing the strength of bringing together different regional voices to promote bilingualism. Code-switching between standard, international French Vancouver students, learn in the classroom versus more regional forms of Quebec French spoken locally created regional connectivity between students. The exchange was equally rewarding for both groups. Increasing their appreciation for each other’s regional differences allowed them to contribute actively to their social and emotional development. Within a sociolinguistic frame, this proposed model of experiential learning does not focus on hands-on work experience. However, the benefits of such exchanges are as valuable as work experience initiatives developed in experiential education. Students who actively code switch between French and English in real, not simulated contexts appreciate bilingualism more meaningfully and experience its value in concrete terms.

Keywords: experiential learning, intercultural communication, social and emotional learning, sociolinguistic code-switching

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Authors: Tamas Garamhegyi, Jozsef Kovacs, Rita Pongracz, Peter Tanos, Balazs Trasy, Norbert Magyar, Istvan G. Hatvani

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Like most environmental processes, shallow groundwater fluctuation under natural circumstances also behaves periodically. With the statistical tools at hand, it can easily be determined if a period exists in the data or not. Thus, the question may be raised: Does the estimated average period time characterize the whole time period, or not? This is especially important in the case of such complex phenomena as shallow groundwater fluctuation, driven by numerous factors. Because of the continuous changes in the oscillating components of shallow groundwater time series, the most appropriate method should be used to investigate its periodicity, this is wavelet spectrum analysis. The aims of the research were to investigate the periodic behavior of the shallow groundwater time series of an agriculturally important and drought sensitive region in Central-Eastern Europe and its relationship to the European pressure action centers. During the research ~216 shallow groundwater observation wells located in the eastern part of the Great Hungarian Plain with a temporal coverage of 50 years were scanned for periodicity. By taking the full-time interval as 100%, the presence of any period could be determined in percentages. With the complex hydrogeological/meteorological model developed in this study, non-periodic time intervals were found in the shallow groundwater levels. On the local scale, this phenomenon linked to drought conditions, and on a regional scale linked to the maxima of the regional air pressures in the Gulf of Genoa. The study documented an important link between shallow groundwater levels and climate variables/indices facilitating the necessary adaptation strategies on national and/or regional scales, which have to take into account the predictions of drought-related climatic conditions.

Keywords: climate change, drought, groundwater periodicity, wavelet spectrum and coherence analyses

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Authors: Vincent Murray

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The chromatin structure at the transcription start sites (TSSs) of genes is very important in the control of gene expression. In order for gene expression to occur, the chromatin structure at the TSS has to be altered so that the transcriptional machinery can be assembled and RNA transcripts can be produced. In particular, the nucleosome structure and positioning around the TSS has to be changed. Bleomycin is utilized as an anti-tumor agent to treat Hodgkin's lymphoma, squamous cell carcinoma, and testicular cancer. Bleomycin produces DNA damage in human cells and DNA strand breaks, especially double-strand breaks, are thought to be responsible for the cancer chemotherapeutic activity of bleomycin. Bleomycin is a large glycopeptide with molecular weight of approximately 1500 Daltons and hence its DNA strand cleavage activity can be utilized as a probe of chromatin structure. In this project, Illumina next-generation DNA sequencing technology was used to determine the position of DNA double-strand breaks at the TSSs of genes in intact cells. In this genome-wide study, it was found that bleomycin cleavage preferentially occurred at the TSSs of actively transcribed human genes in comparison with non-transcribed genes. There was a correlation between the level of enhanced bleomycin cleavage at TSSs and the degree of transcriptional activity. In addition, bleomycin was able to determine the position of nucleosomes at the TSSs of human genes. Bleomycin analogues were also utilized as probes of chromatin structure at the TSSs of human genes. In a similar manner to bleomycin, the bleomycin analogues 6′-deoxy-BLM Z and zorbamycin preferentially cleaved at the TSSs of human genes. Interestingly this degree of enhanced TSS cleavage inversely correlated with the cytotoxicity (IC50 values) of BLM analogues. This indicated that the degree of cleavage by bleomycin analogues at the TSSs of human genes was very important in the cytotoxicity of bleomycin and analogues. It also provided a deeper insight into the mechanism of action of this cancer chemotherapeutic agent since actively transcribed genes were preferentially targeted.

Keywords: anti-cancer activity, chromatin structure, cytotoxicity, gene expression, next-generation DNA sequencing

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Authors: Frank Boris Feutmba Keutchou, Saurelle Fabienne Bieghan Same, Verelle Elsa Fogang Pokam, Charles Ursula Metapi Meikeu, Angel Marilyne Messop Nzomo, Ousman Tamgue

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Infectious diseases are one of the most important causes of morbidity and mortality worldwide. These diseases are caused by micro-pathogenic organisms, such as bacteria, viruses, parasites, and fungi. Heritable changes in gene expression that do not involve changes to the underlying DNA sequence are referred to as epigenetics. Emerging evidence suggests that epigenetic mechanisms are important in the emergence and progression of infectious diseases. Pathogens can manipulate host epigenetic machinery to promote their own replication and evade immune responses. The Human Genome Project has provided new opportunities for developing better tools for the diagnosis and identification of target genes. Several epigenetic modifications, such as DNA methylation, histone modifications, and non-coding RNA expression, have been shown to influence infectious disease outcomes. Understanding the epigenetic mechanisms underlying infectious diseases may result in the progression of new therapeutic approaches focusing on host-pathogen interactions. The goal of this study is to show how different infectious agents interact with host cells after infection.

Keywords: epigenetic, infectious disease, micro-pathogenic organism, phenotype

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Authors: Melaku Tsehay

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The Consortium of Christian Relief and Development Associations (CCRDA), and the CORE Group Polio Partners (CGPP) Secretariat have been working with Global Alliance for Vac-cines and Immunization (GAVI) to improve the immunization data quality in Afar and Somali Regional States. The main aim of this study was to compare the quality of immunization data before and after the above interventions in health facilities in the pastoralist communities in Ethiopia. To this end, a comparative-cross-sectional study was conducted on 51 health facilities. The baseline data was collected in May 2019, while the end line data in August 2021. The WHO data quality self-assessment tool (DQS) was used to collect data. A significant improvment was seen in the accuracy of the pentavalent vaccine (PT)1 (p = 0.012) data at the health posts (HP), while PT3 (p = 0.010), and Measles (p = 0.020) at the health centers (HC). Besides, a highly sig-nificant improvment was observed in the accuracy of tetanus toxoid (TT)2 data at HP (p < 0.001). The level of over- or under-reporting was found to be < 8%, at the HP, and < 10% at the HC for PT3. The data completeness was also increased from 72.09% to 88.89% at the HC. Nearly 74% of the health facilities timely reported their respective immunization data, which is much better than the baseline (7.1%) (p < 0.001). These findings may provide some hints for the policies and pro-grams targetting on improving immunization data qaulity in the pastoralist communities.

Keywords: data quality, immunization, verification factor, pastoralist region

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Authors: Vivianne Aggestam

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Purpose: Organic dairy products have steadily increased with consumer popularity in recent years in Sweden, permitting more transport activities. The main aim of this study was to compare the transport costs and the environmental emissions made by the organic and conventional dairy production in Sweden. The objective was to evaluate differences and environmental impacts of transport between the two different production systems, allowing a more transparent understanding of the real impact of transport within the supply chain. Methods: A partial attributional Life Cycle Assessment has been conducted based on a comprehensive survey of Swedish farmers, dairies and consumers regarding their transport needs and costs. Interviews addressed the farmers and dairies. Consumers were targeted through an online survey. Results: Higher transport inputs from conventional dairy transportation are mainly via feed and soil management on farm level. The regional organic milk brand illustrate less initial transport burdens on farm level, however, after leaving the farm, it had equal or higher transportation requirements. This was mainly due to the location of the dairy farm and shorter product expiry dates, which requires more frequent retail deliveries. Organic consumers tend to use public transport more than private vehicles. Consumers using private vehicles for shopping trips primarily bought conventional products for which price was the main deciding factor. Conclusions: Organic dairy products that emphasise its regional attributes do not ensure less transportation and may therefore not be a more “climate smart” option for the consumer. This suggests that the idea of localism needs to be analysed from a more systemic perspective. Fuel and regional feed efficiency can be further implemented, mainly via fuel type and the types of vehicles used for transport.

Keywords: supply chains, distribution, transportation, organic food productions, conventional food production, agricultural fossil fuel use

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Authors: Elena Maria Scalisi

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The increasing production and the use of TiO₂ nanoparticles (NPs) have inevitably led to their release into the environment, thereby posing a threat to organisms and also for human. Human exposure to TiO₂-NPs may occur during both manufacturing and use. TiO₂-NPs are common in consumer products for dermal application, toothpaste, food colorants, and nutritional supplements, then oral exposure may occur during use of such products. Into the body, TiO₂-NPs thanks to their small size (<100 nm), can, through testicular blood barrier inducing effect on testis and then on male reproductive health. The nanoscale size of TiO₂ increase the surface-to-volume ratio making them more reactive in a cell, then TiO₂ NPs increase their ability to produce reactive oxygen species (ROS). In male germ cells, ROS may have important implications in maintaining the normal functions of mature spermatozoa at physiological levels, moreover, in spermatozoa they are important signaling molecules for their hyperactivation and acrosome reaction. Nevertheless, an excess of ROS by external inputs such as NPs can increased the oxidative stress (OS), which results in damage DNA and apoptosis. The aim of our study has been investigate the impact of TiO₂ NPs on human spermatozoa, evaluating DNA damage and the expression of proteins involved in cell stress. According WHO guidelines 2021, we have exposed human spermatozoa in vitro to TiO₂ NP at concentrations 50 ppm, 100 ppm, 250 ppm, and 500 ppm for 1 hour (at 37°C and CO₂ at 5%). DNA damage was evaluated by Sperm Chromatin Dispersion Test (SCD) and TUNEL assay; moreover, we have evaluated the expression of biomarkers of oxidative stress like Heat Shock Protein 70 (HSP70) and Metallothioneins (MTs). Also, sperm parameters as motility viability have been evaluated. Our results not report a significant reduction in motility of spermatozoa at the end of the exposure. On the contrary, the progressive motility was increased at the highest concentration (500 ppm) and was statistically significant compared to control (p <0.05). Also, viability was not changed by exposure to TiO₂-NPs (p <0.05). However, increased DNA damage was observed at all concentrations, and the TUNEL assay highlighted the presence of single strand breaks in the DNA. The spermatozoa responded to the presence of TiO₂-NPs with the expression of Hsp70, which have a protective function because they allow the maintenance of cellular homeostasis in stressful/ lethal conditions. A positivity for MTs was observed mainly for the concentration of 4 mg/L. Although the biological and physiological function of the metallothionein (MTs) in the male genital organs is unclear, our results highlighted that the MTs expressed by spermatozoa maintain their biological role of detoxification from metals. Our results can give additional information to the data in the literature on the toxicity of TiO₂-NPs and reproduction.

Keywords: human spermatozoa, DNA damage, TiO₂-NPs, biomarkers

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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: Ceyda Okudu, Secil Eroglu, Khandakar A. S. M. Saadat, Sibel O. Balci

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Ring Finger Protein 2 (RNF2) is a member of polycomb repressive complex 1 (PRC1), which is one of the epigenetic regulators in the genome. When RNF2 combines with other PRC1 members, it mediates the mono-ubiquitination of Histon2A (H2A). In breast cancer, RNF2 is commonly overexpressed, and also it promotes metastasis and invasion in other aggressive tumors like melanoma, prostate, and hepatocarcinoma. The role of RNF2 in the metastasis and invasion of breast cancer has not yet been elucidated. Our aim is to observe the role of RNF2 in metastasis and invasion in this study by miRNA mediated RNF2 gene silencing in breast cancer cell lines. We selected miRNAs, targeting to RNF2 by searching online databases. miR-17-5p, miR20a-5p, and miR-106b-5p were transfected to breast cancer cell lines (MCF-7, MDA-MB-231, SK-BR-3, and ZR-75-1), and also we used normal breast epithelial cell line (hTERT-HME1) to compare RNF2 gene expression level. After 48-72 hours post-transfection, mRNAs were isolated from the cells, and gene expressions were measured by RT-qPCR after from cDNA syntheses. We observed that RNF2 was highly expressed in SK-BR-3 and MDA-MB-231 cell lines opposite to MCF-7 and ZR-75-1 cell lines. RNF2 was downregulated 5, 5 and 7 fold by miR17-5p, miR20a-5p and miR106b-5p respectively in MCF-7. However, in SK-BR-3 and ZR-75-1 cell lines, miRNAs did not affect significantly RNF2 gene expression level. miR20a-5p decreased RNF2 3 fold and miR17-5p and miR106b-5p did not affect MDA-MB-231. After gene expression analysis, we performed metastasis and invasion assay in MCF-7 cells. For metastasis, we used both wound healing assay and Transwell Cell Migration Assay, and we used Transwell Cell Invasion Assay for invasion. The data of this assay showed that miR17-5p and miR20a-5p decreased both invasion and metastasis level, but miR106b-5p has no effect. We would like to conclude that RNF2 can be targeted by miR17-5p, miR20a-5p and miR106b-5p in MCF-7 cells and also RNF2, which is one of the upregulated genes in aggressive tumor, can be decreased by using these miRNAs. In future, we would like to confirm these results at the protein level and also whether these miRNAs are direct target of RNF2 or not.

Keywords: breast cancer, epigenetic, microRNAs, RNF2

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Authors: Gizaw Mamo Gebeyehu, Marianna Pap, Geza Makkai, Tibor Z. Janosi, Shima Rashidian, Tibor A. Rauch

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Sepsis poses a significant global health threat, necessitating extensive exploration of indicators tied to its pathological mechanisms and multi-organ dysfunction. While murine studies have shed light on sepsis, the intricate cellular and molecular landscape in human sepsis remains enigmatic. Exploring the influence of activated monocyte-derived exosomes in sepsis sheds light on a promising pathway for understanding the intricate cellular and molecular mechanisms involved in this condition in humans. In sepsis, exosome-borne mRNA and miRNA orchestrate immune response gene expression in recipient cells. Yet, the specifics of exosome-mediated cell-to-cell communication, especially how mRNA cargoes modulate gene expression in recipient cells, remain poorly understood. This study aims to elucidate the precise molecular pathways through which exosomal mRNA cargo, particularly MAFB, contributes to the developing sepsis-induced molecular aberrations in liver tissues, employing rigorously defined cell culture conditions. THP-1 cells were treated with LPS to induce changes in exosomal RNA profiles. Exosomes were isolated and characterized using microscopy and mass spectrometry. RNA was extracted from exosomes and sequenced. The most abundant exosomal mRNAs were subjected to GO analysis for functional annotation analysis and KEGG database analysis to identify the involved enriched pathways. PCR (Polymerase Chain Reaction), RNA sequencing, and Western blotting were involved to analyze changes in gene expression, protein levels, and signaling pathways within the liver cells( HepG2) after exposure to exosomal MAFB. This study pinpoints exosomal MAFB as a potential key regulator linked to liver cell damage during sepsis, along with associated genes (miR155HG, H3F3A, and possibly JARD2) forming a crucial molecular pathway contributing to liver cell injury, Together, these elements indicate a vital molecular pathway that plays a significant role in the emergence of liver cell injury during sepsis.. These findings suggest the importance of further research on these components for potential therapeutic interventions in managing acute liver damage in sepsis.

Keywords: sepsis, exososome, exosomal MAFB, LPS-induced THP-1 cells, RNA profiles, sepsis-triggered liver injury

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Authors: Neha Singh, Ananya Arora

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Facial expression measurement plays a crucial role in the identification of emotion. Facial expression plays a key role in psychophysiology, neural bases, and emotional disorder, to name a few. The Facial Action Coding System (FACS) has proven to be the most efficient and widely used of the various systems used to describe facial expressions. Coders can manually code facial expressions with FACS and, by viewing video-recorded facial behaviour at a specified frame rate and slow motion, can decompose into action units (AUs). Action units are the most minor visually discriminable facial movements. FACS explicitly differentiates between facial actions and inferences about what the actions mean. Action units are the fundamental unit of FACS methodology. It is regarded as the standard measure for facial behaviour and finds its application in various fields of study beyond emotion science. These include facial neuromuscular disorders, neuroscience, computer vision, computer graphics and animation, and face encoding for digital processing. This paper discusses the conceptual basis for FACS, a numerical listing of discrete facial movements identified by the system, the system's psychometric evaluation, and the software's recommended training requirements.

Keywords: facial action, action units, coding, machine learning

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Authors: Xuan Hua Huang, Shu Fen Wu, Yi Ting Huang, Pi Yueh Lee

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Background: In Taiwan, the Taiwan healthcare care Indicator Series regards the rate of hospital readmission as an important indicator of healthcare quality. Unplanned readmission not only effects patient’s condition but also increase healthcare utilization rate and healthcare costs. Purpose: The purpose of this study was explored the effects of adult unplanned readmission within 14 days of discharge at a regional teaching hospital in South Taiwan. Methods: The retrospectively review design was used. A total 495 participants of unplanned readmissions and 878 of non-readmissions within 14 days recruited from a regional teaching hospital in Southern Taiwan. The instruments used included the Charlson Comorbidity Index, and demographic characteristics, and disease-related variables. Statistical analyses were performed with SPSS version 22.0. The descriptive statistics were used (means, standard deviations, and percentage) and the inferential statistics were used T-test, Chi-square test and Logistic regression. Results: The unplanned readmissions within 14 days rate was 36%. The majorities were 268 males (54.1%), aged >65 were 318 (64.2%), and mean age was 68.8±14.65 years (23-98years). The mean score for the comorbidities was 3.77±2.73. The top three diagnosed of the readmission were digestive diseases (32.7%), respiratory diseases (15.2%), and genitourinary diseases (10.5%). There were significant relationships among the gender, age, marriage, comorbidity status, and discharge planning services (χ2: 3.816-16.474, p: 0.051~0.000). Logistic regression analysis showed that old age (OR = 1.012, 95% CI: 1.003, 1.021), had the multi-morbidity (OR = 0.712~4.040, 95% CI: 0.559~8.522), had been consult with discharge planning services (OR = 1.696, 95% CI: 1.105, 2.061) have a higher risk of readmission. Conclusions: This study finds that multi-morbidity was independent risk factor for unplanned readmissions at 14 days, recommended that the interventional treatment of the medical team be provided to provide integrated care for multi-morbidity to improve the patient's self-care ability and reduce the 14-day unplanned readmission rate.

Keywords: unplanned readmission, comorbidities, Charlson comorbidity index, logistic regression

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Authors: E. Zarei, M. Bazaei, A. Seifi, A. Keshavarzi

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Amos Rapoport, based on his anthropology approach, believed that the space origins from the human body and influences on human body mutually. As a holistic approach in architecture, Contextualism describes a collection of views in philosophy which emphasize the context in which an action, utterance, or expression occurs, and argues that, in some important respect, the action, utterance, or expression can only be understood relative to that context. In this approach, the main goal – studying the role of cultural component in the Contextualism construction shaping up, based on Amos Rapoport’s anthropology approach- has being done by descriptive- analytic method. The results of the research indicate that in the field of Contextualism designing, referring to the cultural aspects are as necessary as the physical dimensions of a construction. Rapoport believes that the shape of a construction is influenced by cultural aspects and he suggests a kind of mutual interaction between human and environment that should be considered in housing. The mail goal of contextual architecture is to establish an interaction between environment, human and culture. According to this approach, a desirable design should be in harmony with this approach.

Keywords: Amos Rapoport, anthropology, contextual architecture, culture

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Authors: Etibar Guliyev

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The breakdown of the Soviet Union in 1991 has led to a considerable rise in the religious self-consciousness of Muslim population of the Central Asia. Additionally, huge amount of money spent by various states further facilitated the spread of religious ideas. According to some sources, Saudi Arabia spent 87 billion dollars to propagate Wahhabism abroad during two decades, whereas the Communist Party of the Soviet Union spent just over 7 billion dollars to spread its ideology worldwide between 1921 and 1991. As the result, today once a remote area from international politics has turned into third major source of recruitment of fighters for global terrorist organizations. In order to illustrate to scope of the involvement of the Central Asian residents in international terrorist networks it is enough to mention the name of Colonel Gulmorod Khalimov, the former head of the Tajik special police forces who served as ISIS war minister between 2016 and 2017. The importance of the topic stems from the fact that the above-mentioned republics with a territory of 4 million square km and the population of around 80 million people borders Russia, Iran Afghanistan and China. Moreover, the fact that political and military activities motivated with religious feelings in those countries have implications not only for domestic but also for regional and global political relations and all of them has root in politics of religions adds value to the research. This research aims to provide an in-depth analyses of the marked features of the state policies to regulate religious activities and approach this question both from individual, domestic, regional and global levels of analyses. The research will enable us to better understand what implications have the state of religious freedom in post-Soviet Muslim republics for international relations and the rise of global jihadi terrorism. The paper tries to find a linkage between the mentioned terror attacks and underground rise of religious extremism in Central Asia. This research is based on multiple research methods, mainly on qualitative one. The process tracing method is also employed to review religious policies implemented from 1918-1991 and after the collapse of the Soviet Union in a chronological way. In terms of the quantitative method, it chiefly will be used in a bid to process various statistics disseminated in academic and official sources. The research mostly explored constructivist, securitization and social movement theories. Findings of the research suggests that the endemic problems peculiar to authoritarian regimes of Central Asia such as crackdown on the expression of religious believe and any kind of opposition, economic decline, instrumental use of religion and corruption and tribalism further accelerated the recruitment problem. Paper also concludes that the Central Asian states in some cases misused counter-terrorism campaign as a pretext to further restrict freedom of faith in their respective countries.

Keywords: identity, political Islam, religious extremism, security, terrorism

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Authors: Hailiang Liu, Yan Ni, Jie Zheng, Xiaoyan Jiang, Min Hong

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Allergic contact dermatitis (ACD) is a commonly clinical type IV allergic skin disease, with the pathological features of infiltration by mononuclear cells and tissue necrosis. Traditional Chinese medicine Radix Saposhnikoviae (RS) is traditionally employed to treat exogenous evils, rubella, itching, rheumatism and tetanus. Meanwhile, it is an important component of the commonly used anti-allergy compound. It’s now widely used as an immuno-modulating agent in mixed herbal decoctions to treat inflammation. However, its mechanism of anti-allergy remains unknown. RS was found to reduce ear thickness, as well as the infiltration of eosinophils. The proliferation of T lymphocytes was inhibited significantly by RS, markedly decreased IFN-γ levels in the supernatant of cells cultured and serum were detected with the treatment of RS. RS significantly decreased the amount of DCs in the mouse lymph nodes, and inhibited the expression of CD4 0 and CD86. Meanwhile, T-bet mRNA expression was down remarkably regulated by RS. These results indicate that RS cures Th1-induced allergic skin inflammation by regulating Th1/Th2 balance with decreasing Th1 differentiation, which might be associated with DCs.

Keywords: allergic contact dermatitis, Radix saposhnikoviae, dendritic cells, T-bet, GATA-3, CD4+ CD25+ Foxp3+ treg cells

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Authors: Eric Bang

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Interactions between receptors and ligands are crucial for many essential biological processes, including neurotransmission and metabolism. Ligand-receptor analyses that examine cell behavior and interactions often utilize cell type-specific RNA expressions from single-cell RNA sequencing (scRNA-seq) data. Using CellPhoneDB, a public repository consisting of ligands, receptors, and ligand-receptor interactions, the cell-cell interactions were explored in a specific scRNA-seq dataset from kidney tissue and portrayed the results with dot plots and heat maps. Depending on the type of cell, each ligand-receptor pair was aligned with the interacting cell type and calculated the positori probabilities of these associations, with corresponding P values reflecting average expression values between the triads and their significance. Using single-cell data (sample kidney cell references), genes in the dataset were cross-referenced with ones in the existing CellPhoneDB dataset. For example, a gene such as Pleiotrophin (PTN) present in the single-cell data also needed to be present in the CellPhoneDB dataset. Using the single-cell transcriptomics data via slide-seq and reference data, the CellPhoneDB program defines cell types and plots them in different formats, with the two main ones being dot plots and heat map plots. The dot plot displays derived measures of the cell to cell interaction scores and p values. For the dot plot, each row shows a ligand-receptor pair, and each column shows the two interacting cell types. CellPhoneDB defines interactions and interaction levels from the gene expression level, so since the p-value is on a -log10 scale, the larger dots represent more significant interactions. By performing an interaction analysis, a significant interaction was discovered for myeloid and T-cell ligand-receptor pairs, including those between Secreted Phosphoprotein 1 (SPP1) and Fibronectin 1 (FN1), which is consistent with previous findings. It was proposed that an effective protocol would involve a filtration step where cell types would be filtered out, depending on which ligand-receptor pair is activated in that part of the tissue, as well as the incorporation of the CellPhoneDB data in a streamlined workflow pipeline. The filtration step would be in the form of a Python script that expedites the manual process necessary for dataset filtration. Being in Python allows it to be integrated with the CellPhoneDB dataset for future workflow analysis. The manual process involves filtering cell types based on what ligand/receptor pair is activated in kidney cells. One limitation of this would be the fact that some pairings are activated in multiple cells at a time, so the manual manipulation of the data is reflected prior to analysis. Using the filtration script, accurate sorting is incorporated into the CellPhoneDB database rather than waiting until the output is produced and then subsequently applying spatial data. It was envisioned that this would reveal wherein the cell various ligands and receptors are interacting with different cell types, allowing for easier identification of which cells are being impacted and why, for the purpose of disease treatment. The hope is this new computational method utilizing spatially explicit ligand-receptor association data can be used to uncover previously unknown specific interactions within kidney tissue.

Keywords: bioinformatics, Ligands, kidney tissue, receptors, spatial transcriptome

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Authors: A. Vijayendra Chary, R. Hemalatha

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Background: Vitamin D is a potent modulator of the immune system and is involved in regulating cell proliferation and differentiation. Vitamin D deficiency has been linked to increased severity of asthma in children. Asthma has dramatically increased in past decades, particular in developing countries and affects up to 20% of the population. IgE and its receptors, CD23 (FcεRII) and CD 21, play an essential role in all allergic conditions. Methods: A case control study was conducted on asthma and age and sex matched control children. 25 hydroxyvitamin D3 was quantified by HPLC; CD23; and CD21 expression on B cells were performed by flow cytometry. Total Histamine, total IGE and IL-5 and IFN-γ cytokines were determined by ELISA in blood samples of bronchial asthma (n=45) and control children (n=45). Results: The mean ± SE of vitamin D was significantly (p<0.05) low in asthma children (13.6±0.54 ng/mL) than in controls (17.4 ± 0.37 ng/mL). The mean (%) ± SE of CD23 and CD21 expression on B cells were significantly (p<0.01) high in asthma (1.02±0.09; 1.67± 0.13), when compared to controls (0.24±0.01; 0.94±0.03) respectively. The mean± SE of Serum IgE and blood histamine levels in asthma children (354.52 ± 17.33 IU/mL; 53.27 ± 2.54 nM/mL) were increased (P<0.05) when compared to controls (183.12±17.62 IU/mL 39.34±4.16 nM/mL) respectively and IFN-γ (Th1 cytokine) was lower (P<0.01) (16.37±1.27 pg/mL) than in controls (43.34±6.21 pg/mL). Conclusion: Our study provides evidence that low vitamin D levels are associated with increased IgE receptors CD23 and CD21 on B cells. In addition, there was preferential activation of Th2 (IL-5) and suppression of Th1 (IFN-γ) cytokines in children with asthma.

Keywords: bronchial asthma, CD23, IgE, vitamin D

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Authors: Ebru Thwaites Diken

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This article analyzes the works of certain directors in Danish cinema, namely Susanne Bier and Lone Sherfig, in the context of transnationalisation of Danish cinema. It looks at how the films' narratives negotiate and reconstruct the local / national / regional and the global. Scholars such as Nestingen & Elkington (2005), Hjort (2010), Higbee and Lim (2010), Bondebjerg and Redvall (2011) address transnationalism of Danish cinema in terms of production and distribution processes and how film making trascends national boundaries. This paper employs a particular understanding of transnationalism - in terms of how ideas and characters travel - to analyze how the storytelling and style has evolved to connect the national, the regional and the global on the basis of the works of these two directors. Strategies such as Hollywoodization - i.e. focus on stardom and classical narration, adhering to conventional European genre formulas, producing Danish films in English language have been identifiable strategies in Danish cinema in the period after the 2000s. Susanne Bier and Lone Scherfig are significant for employing some of these strategies simultaneously. For this reason, this article will look at how these two directors have employed these strategies and negotiated the cultural boundaries and exchanges.

Keywords: danish cinema, transnational cinema, susanne bier, lone scherfig, national cinema

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Authors: Alan S. Hoback

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Most people see human faces in car front and back ends because of the process of pareidolia. 96 people were surveyed to see how many of them saw a face in the vehicle styling. Participants were aged 18 to 72 years. 94% of the participants saw faces in the front-end design of production models. All participants that recognized faces indicated that most styles showed some degree of an angry expression. It was found that women were more likely to see faces in inanimate objects. However, with respect to whether women were more likely to perceive anger in the vehicle design, the results need further clarification. Survey responses were correlated to the design features of vehicles to determine what cues the respondents were likely looking at when responding. Whether the features looked anthropomorphic was key to anger perception. Features such as the headlights which could represent eyes and the air intake that could represent a mouth had high correlations to trends in scores. Results are compared among models, makers, by groupings of body styles classifications for the top 12 brands sold in the US, and by year for the top 20 models sold in the US in 2016. All of the top models sold increased in perception of an angry expression over the last 20 years or since the model was introduced, but the relative change varied by body style grouping.

Keywords: aggressive driving, face recognition, road rage, vehicle styling

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Authors: Wenxing Chen, Guangying Chen, Yin Lu, Shile Huang

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Cryptotanshinone (CPT), a fat-soluble tanshinone from Salvia miltiorrhiza Bunge, has been demonstrated to inhibit mTOR pathway, resulting in inhibition of cancer cell proliferation. However, the molecular mechanism how CPT acts on mTOR is unknown. Here, cancer cells expressing rapamycin-resistant mutant mTOR are also sensitive to CPT, while phosphorylation of AMPK and TSC2 was activated, suggesting that CPT inhibition of mTOR maybe due to activating upstream of mTOR, AMPK, but not directly binding to and inhibiting mTOR. Further results indicated that Compound C, inhibitor of AMPK, could partially reversed CPT inhibition effect on cancer cells, and dominant-negative AMPK in cancer cells conferred resistance to CPT inhibition of 4EBP1 and phosphorylation of S6K1, as well as sh-AMPK. Furthermore, compared with MEF cells with AMPK positive, MEF cells with AMPK knock out are less sensitive to CPT by the findings that 4E-BP1 and phosphorylation of S6K1 express comparatively much. Furthermore, downexpression of TSC2 slightly recovered expression of 4EBP1 and phosphorylation of S6K1, while co-immunoprecipitation of TSC2 did not affect expression of TSC1 by CPT. Collectively, the above-mentioned results suggest that CPT inhibited mTOR pathway mostly was due to activation of AMPK-TSC2 pathway rather than specific inhibition of mTOR and then induction of subsequent lethal cellular effect.

Keywords: cryptotanshinone, AMPK, TSC2, mTOR, cancer cells

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Authors: Aditya Arya, Hairin Taha, Ataul Karim Khan, Nayiar Shahid, Hapipah Mohd Ali, Mustafa Ali Mohd

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This study has investigated the antidiabetic and antioxidant potential of Pseudovaria macrophylla bark extract on streptozotocin–nicotinamide induced type 2 diabetic rats. LCMS-QTOF and NMR experiments were done to determine the chemical composition in the methanolic bark extract. For in vivo experiments, the STZ (60 mg/kg/b.w, 15 min after 120 mg/kg/1 nicotinamide, i.p.) induced diabetic rats were treated with methanolic extract of Pseuduvaria macrophylla (200 and 400 mg/kg∙bw) and glibenclamide (2.5 mg/kg) as positive control respectively. Biochemical parameters were assayed in the blood samples of all groups of rats. The pro-inflammatory cytokines, antioxidant status and plasma transforming growth factor βeta-1 (TGF-β1) were evaluated. The histological study of the pancreas was examined and its expression level of insulin was observed by immunohistochemistry. In addition, the expression of glucose transporters (GLUT 1, 2 and 4) were assessed in pancreas tissue by western blot analysis. The outcomes of the study displayed that the bark methanol extract of Pseuduvaria macrophylla has potentially normalized the elevated blood glucose levels and improved serum insulin and C-peptide levels with significant increase in the antioxidant enzyme, reduced glutathione (GSH) and decrease in the level of lipid peroxidation (LPO). Additionally, the extract has markedly decreased the levels of serum pro-inflammatory cytokines and transforming growth factor beta-1 (TGF-β1). Histopathology analysis demonstrated that Pseuduvaria macrophylla has the potential to protect the pancreas of diabetic rats against peroxidation damage by downregulating oxidative stress and elevated hyperglycaemia. Furthermore, the expression of insulin protein, GLUT-1, GLUT-2 and GLUT-4 in pancreatic cells was enhanced. The findings of this study support the anti-diabetic claims of Pseudovaria macrophylla bark.

Keywords: diabetes mellitus, Pseuduvaria macrophylla, alkaloids, caffeic acid

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Authors: Anjali Roy, Mirza S. Baig

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Atherosclerosis is a chronic inflammatory disease characterized by the formation of lipid rich plaque enriched with necrotic core, modified lipid accumulation, smooth muscle cells, endothelial cells, leucocytes and macrophages. Macrophage foam cells play a critical role in the occurrence and development of inflammatory atherosclerotic plaque. Foam cells are the fat-laden macrophages in the initial stage atherosclerotic lesion formation. Foam cells are an indication of plaque build-up, or atherosclerosis, which is commonly associated with increased risk of heart attack and stroke as a result of arterial narrowing and hardening. The mechanisms that drive atherosclerotic plaque progression remain largely unknown. Dissecting the molecular mechanism involved in process of macrophage foam cell formation will help to develop therapeutic interventions for atherosclerosis. To investigate the mechanism, we studied the role of nitric oxide synthase 1(NOS1)-mediated nitric oxide (NO) on low-density lipoprotein (LDL) uptake by bone marrow derived macrophages (BMDM). Using confocal microscopy, we found that incubation of macrophages with NOS1 inhibitor, TRIM (1-(2-Trifluoromethylphenyl) imidazole) or L-NAME (N omega-nitro-L-arginine methyl ester) prior to LDL treatment significantly reduces the LDL uptake by BMDM. Further, addition of NO donor (DEA NONOate) in NOS1 inhibitor treated macrophages recovers the LDL uptake. Our data strongly suggest that NOS1 derived NO regulates LDL uptake by macrophages and foam cell formation. Moreover, we also checked proinflammatory cytokine mRNA expression through real time PCR in BMDM treated with LDL and copper oxidized LDL (OxLDL) in presences and absences of inhibitor. Normal LDL does not evoke cytokine expression whereas OxLDL induced proinflammatory cytokine expression which significantly reduced in presences of NOS1 inhibitor. Rapid NOS-1-derived NO and its stable derivative formation act as signaling agents for inducible NOS-2 expression in endothelial cells, leading to endothelial vascular wall lining disruption and dysfunctioning. This study highlights the role of NOS1 as critical players of foam cell formation and would reveal much about the key molecular proteins involved in atherosclerosis. Thus, targeting NOS1 would be a useful strategy in reducing LDL uptake by macrophages at early stage of disease and hence dampening the atherosclerosis progression.

Keywords: atherosclerosis, NOS1, inflammation, oxidized LDL

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Authors: Xi Zhang, Yong Geng

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It is crucial to decouple economic growth from environmental pollution in China. This study aims to evaluate the decoupling degree between PM₂.₅ emissions and economic growth in China from a regional investment perspective. Using the panel data of 30 Chinese provinces for the period of 1998-2016, this study combines decomposition analysis with decoupling analysis to identify the roles of conventional factors and three novel investment factors in the mitigation and decoupling of PM₂.₅ emissions in China and its four sub-regions. The results show that China’s PM₂.₅ emissions were weakly decoupled to economic growth during the period of 1998-2016, as well as in China’s four sub-regions. At the national level, investment scale played the dominant role while investment structure had a marginal effect. In contrast, emission intensity was the largest driver in promoting the decoupling effect, followed by investment efficiency and energy intensity. The investment scale effect in the western region far exceeded those in other three sub-regions. At the provincial level, the investment structure of Inner Mongolia and investment scales of Xinjiang and Inner Mongolia had the greatest impacts on PM₂.₅ emission growth. Finally, several policy recommendations are raised for China to mitigate its PM₂.₅ emissions.

Keywords: decoupling, economic growth, investment, PM₂.₅ emissions

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