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The present study investigated the production of the speech act of disagreement among Tunisian non-native students of English and American native speakers of English. Discourse completion test (DCT) was used to elicit disagreement strategies by the informants. Non-native informants produced a total of 376 acts and native informants produced 395 acts. The acts were categorized based on Brown and Levinson's (1987) Politeness Model. The speakers' performance of disagreement in variation with the contextual factors of Social Distance and Social Power was examined. Data was analyzed quantitatively and qualitatively. Results showed that there were significant differences between native and non-native speakers of English with regard to the frequency of direct and indirect strategies of disagreement. Non-native informants used a higher percentage of direct strategies (47%) and a lower percentage of indirect strategies (13%) than their native counterparts, who produced indirect strategies considerably (30%). NNSE opting for direct disagreement strategies might be attributed to their poor pragmatic and sociolinguistic knowledge of indirect strategies. This work can have pedagogical implications in teaching speech acts and pragmatics.

Introduction Agriculture plays an essential role in providing food, and in order to achieve sustainability in the agricultural sector, resources must be used in the best possible way. In order to achieve the maximum possible yield, it is necessary for the crop plant to use the environmental factors, water, nutrients, light, and carbon dioxide, with the maximum possible efficiency. The maximum use of the required factors for growth is achieved only when the plant community exerts maximum pressure on these factors. In general, intercropping is one of the ways to achieve sustainable agriculture, with higher yields without increasing agricultural inputs, absorption, and environmental factors productivity. Researchers for the intercropping of corn and mung bean have reported that the mixed cultivation systems used environmental resources more effectively compared to the sole cropping of corn and mung bean. For this reason, nowadays, many plants, especially legumes, are cultivated in an intercropping form due to their ability to fix nitrogen. Due to the lack of resources regarding the effect of planting direction on plant yield, this study was conducted in order to evaluate resources and soil nutrients by changing the planting direction and replacing the intercropping system of the sunflower with cowpea. Materials and Methods This research was conducted in the field of the Agricultural Research Station of Zabol University during 2015-2016. The experiment was performed as a split-plot based on a randomized complete block design with three replications at the Research Farm of the Agricultural Research Institute of Zabol University. The main factor was two levels of planting direction (North-South and East-West), and the secondary factor was intercropping system in five levels, including (100% pure sunflower), (100% pure cowpea ), (50% sunflower + 50% cowpea ) (25% cowpea + 75% sunflower) and (75 % cowpea + 25%sunflower) were considered. Data for studied traits were measured as follows: radiation, temperature, volumetric humidity, calcium, phosphorus, magnesium, potassium, and the land equality ratio. Statistical analysis including, analysis of variance and mean comparisons (least significant difference (LSD) test at the 5% level), were applied to evaluated traits. Results and Discussion The maximum absorption of photosynthetically active radiation (PAR) was in the east-west cultivation direction (77.90%) compared to the north-south treatment, which was 24.6% more than the north-south direction. The analysis of variance indicated that the cultivation direction and intercropping systems on the amount of phosphorus in the soil after harvest were significant at 1% probability level. The comparison of means treatments showed that the amount of phosphorus in the soil in the direction of east-west cultivation was 15% higher compared to the direction of north-south cultivation. The highest amount of soil potassium was obtained in the east-west treatment and the intercropping system of 50% sunflower plus 50% cowpea (24.7 ppm). The lowest amount of soil potassium (16.15 ppm) was obtained in the treatment of east-west cultivation and the intercropping system of 75% sunflower plus 25% cowpea. The relative advantage of intercropping is expressed by the land equivalent ratio. The increase in the ratio of equal land per unit shows the relative usefulness of intercropping compared to sole cropping of each of the mixed components. The comparison of means of the intercropping system showed that among the treatments, the mixture of 75% sunflower plus 25% cowpea had the highest land equivalent ratio (2.54). Conclusion It seems that in order to maintain humidity make maximum use of limited water resources, and obtain high yield, the intercropping system of 75% sunflower plus 25% cowpea and planting direction the prevailing wind of the region (east-west) should be suitable for this region and regions with similar climate and windy conditions. Acknowledgments We would like to thank the chairman and the respected staff of the Agricultural Research Institute of Zabul University, who sincerely accompanied us in the implementation of this thesis.

Acne in adult females is triggered mainly by hormones. Doxycycline is a reference treatment in acne. Spironolactone targets the androgen receptor of sebaceous glands and is prescribed off-label for female adult acne. This multicentre, controlled, randomized, double-blind prospective and parallel study assessed the efficacy of spironolactone compared with doxycycline in adult female acne. A total of 133 women with moderate acne were randomized to receive treatment with: (i) doxycycline and benzoyl peroxide for 3 months followed by a 3-month treatment with its placebo and benzoyl peroxide, or (ii) spironolactone and benzoyl peroxide for 6 months. Successfully treated patients continued with benzoyl peroxide or spironolactone alone for a further 6 months. Primary endpoints were treatment success at month 4 and month 6 with the AFAST score. At all visits, the ECLA score, lesion counts, local and systemic safety and quality of life were assessed. Spironolactone performed better at month 4 and showed a statistically significant better treatment success after 6 months than doxycycline (p = 0.007). Spironolactone was 1.37-times and 2.87-times more successful compared with doxycycline at respective time-points. AFAST and ECLA scores, as well as lesion counts always improved more with spironolactone. Patients’ quality of life was better with spironolactone at month 4 and month 6. Spironolactone was very well tolerated. This is the first study to show that, in female adults with moderate acne, treatment with spironolactone is significantly more successful than doxycycline and very well tolerated.

Abstract Background Adoptive cell therapy (ACT) has emerged as an effective treatment for patients with metastatic melanoma. However, there are several logistical and safety concerns associated with large-scale ex vivo expansion of tumour-specific T lymphocytes for widespread availability of ACT for cancer patients. To address these problems we developed a specific compartmentalised bag allowing efficient expansion of tumour-specific T lymphocytes in an easy handling, closed system. Methods Starting from lymph nodes from eight melanoma patients, we performed a side-by-side comparison of Tumour-Infiltrating Lymphocytes (TIL) produced after expansion in the compartmentalised bag versus TIL produced using the standard process in plates. Proliferation yield, viability, phenotype and IFNγ secretion were comparatively studied. Results We found no differences in proliferation yield and cell viability between both TIL production systems. Moreover, each of the cell products complied with our defined release criteria before being administered to the patient. The phenotype analysis indicated that the compartmentalised bag favours the expansion of CD8+ cells. Finally, we found that TIL stimulated in bags were enriched in reactive CD8+ T cells when co-cultured with the autologous melanoma cell line. Conclusions The stimulation of TIL with feeder cells in the specifically designed compartmentalised bag can advantageously replace the conventional protocol using plates. In particular, the higher expansion rate of reactive CD8+ T cells could have a significant impact for ACT.

Background Undoubtedly, the importance of food and food security as one of the present and future challenges is not invisible to anyone. Nowadays, the development of methods for monitoring the nutrient content in crop products is an essential issue for implementing reasonable and logical soil properties management. The modeling technique can evaluate the soil properties of fields and study the subject of crop yield through soil management. This study aims to predict fruit yield and macro-nutrient content in plant organs of Cucumis melo in response to soil elements using support vector regression (SVR). Methodology In the spring of 2020, this study was done as a factorial test in a randomized complete block design with three replications. The first factor was the use of fertilizers in six levels: no fertilizer (control), cow manure (30 t ha−1), sheep manure (30 t ha−1), nanobiomic foliar application (2 l ha−1), silicone foliar application (3 l ha−1), and chemical fertilizer from urea, triple superphosphate, and potassium sulfate sources (200, 100, and 150 kg ha−1). In addition, four levels of vermicompost considering as the second factor: no vermicompost (control), 5, 10, and 15 t ha−1. Input data sets such as fruit yield and nitrogen, phosphorus, and potassium levels in the seeds, fruits, leaves, and roots are used to calibrate the probabilistic model of SP using SVR. Results According to the results, when the data sets of the nitrogen, phosphorus, and potassium in the fruit uses as input, the accuracy of these models was higher than 80.0% (R2 = 0.807 for predicting fruit nitrogen; R2 = 0.999 for fruit phosphorus; R2 = 0.968 for fruit potassium). Also, the results of the prediction models in response to soil elements showed that the soil nitrogen content ranged from 0.05 to 1.1%, soil phosphorus from 10 to 59 mg kg−1, and soil potassium from 180 to 320 mg kg−1, which offers a suitable macro-nutrient content in the soil. Likewise, the best fruit nitrogen content ranged from 1.27 to 4.33%, fruit phosphorus from 15.74 to 26.19%, fruit potassium from 15.19 to 19.67%, and fruit yield from 2.16 to 5.95 kg per plant obtained under NPK chemical fertilizers and using 15 t ha−1 of vermicompost. Conclusions Because the fruit values had the highest contribution in prediction than observed values, thus identified as the best plant organs in response to soil elements. Based on our findings, the importance of fruit phosphorus identifies as a determinant that strongly influenced melon prediction models. More significant values of soil elements do not affect increasing fruit yield and macro-nutrient content in plant organs, and excessive application may not be economical. Therefore, our studies provide an efficient approach with potentially high accuracy to estimate fruit yield and macro-nutrient in the fruits of Cucumis melo in response to soil elements and cause a saving in the amount of fertilizer during the growing season.

Background: Acne vulgaris is a chronic inflammatory dermatosis. Cutibacterium acnes plays a crucial role in the acne pathophysiology. Recent works present evidence of C. acnes growing as a biofilm in cutaneous follicles. This development is currently considered one of the leading causes of C. acnes in vivo persistence and resistance to antimicrobials used to treat acne. Objective: Our objective was to evaluate the effects of various active compounds (clindamycin, erythromycin, doxycycline, and myrtle extract) on eight distinct, well‐characterized strains of C. acnes following their growth in biofilm mode. Methods/Results: Cutibacterium acnes isolates from phylotypes IA1 and IA2 produce more biofilm than other phylotypes. No antibiotic effect was observed either during the curative test or preventive test. Myrtle extract at 0.01% (w/v) showed significant efficacy on the biofilm for C. acnes strains (curative assays). Furthermore, it appear that myrtle extract and doxycycline together reduce the overall biomass of the biofilm. A significant dose‐dependent effect was observed during the preventive test, greater than the one observed under curative conditions, with an important loss of activity of the myrtle extract observed from 0.001% (w/v) concentration onwards. Transmission electron microscopy showed that bacteria treated with myrtle extract grew biofilms much less frequently than untreated bacteria. Additionally, when the quantity of myrtle extract grew, the overall number of bacteria dropped, indicating an additional antibacterial action. Conclusion: These findings support the hypothesis that the different C. acnes phylotypes have various aptitudes in forming biofilms. They also suggest that myrtle extract is a promising alternative as an anti‐biofilm and antibacterial agent in fighting diseases caused by planktonic and biofilm C. acnes. [ABSTRACT FROM AUTHOR]

Abstract This paper presents a simple and robust hybrid combiner for the multiuser massive multiple‐input multiple‐output (MIMO) uplink. The hybrid beamforming is used in massive MIMO systems to reduce the number of radio frequency chains. Radio frequency chain consists of power hungry electronic components like mixer, analog‐to‐digital converter / digital‐to‐analog converter etc. This paper proposes a Householder based hybrid beamforming (HHBF) design to simultaneously reduce the beam domain inter‐user interference and increase the sum‐rate performance of massive MIMO uplink. The Householder reflectors generate the orthogonal analog combiner matrix which not only reduces inter‐user interference but also helps reduce the dimension of the digital combiner. It has been shown that the proposed HHBF scheme provides better sum‐rate performance than the Gram–Schmidt based hybrid beamforming design in the real‐World ill‐conditioned MIMO channel. Simulation results show that the beam domain orthogonality error remains less than 0.5 with 0.97 probability and the proposed HHBF provides 25.95% increased sum‐rate at 10 dB SNR.

Immune checkpoint blockers (ICB) have become pivotal therapies in the clinical armamentarium against metastatic melanoma (MMel). Given the frequency of immune related adverse events and increasing use of ICB, predictors of response to CTLA-4 and/or PD-1 blockade represent unmet clinical needs. Using a systems biology-based approach to an assessment of 779 paired blood and tumor markers in 37 stage III MMel patients, we analyzed association between blood immune parameters and the functional immune reactivity of tumor-infiltrating cells after ex vivo exposure to ICB. Based on this assay, we retrospectively observed, in eight cohorts enrolling 190 MMel patients treated with ipilimumab, that PD-L1 expression on peripheral T cells was prognostic on overall and progression-free survival. Moreover, detectable CD137 on circulating CD8+ T cells was associated with the disease-free status of resected stage III MMel patients after adjuvant ipilimumab + nivolumab (but not nivolumab alone). These biomarkers should be validated in prospective trials in MMel.The clinical management of metastatic melanoma requires predictors of the response to checkpoint blockade. Here, the authors use immunological assays to identify potential prognostic/predictive biomarkers in circulating blood cells and in tumor-infiltrating lymphocytes from patients with resected stage III melanoma.

Acne is a common benign inflammatory disease, but it has a significant psychosocial impact. The role of the diet in the development of acne is controversial. Some daily foods such as milk and fast-release sugars tend to promote acne. The Mediterranean Diet (MD) is based on virgin olive oil and nuts that are rich in polyphenols with anti-inflammatory properties. The aim of this study was to assess an association between the adherence to the MD and the severity of facial acne in French women. A case-control observational study was conducted in Nantes Hospital (France). Based on a validated PREvención con DIeta MEDiterránean questionnaire, the adherence to the MD was assessed. The Global Evaluation Acne severity score was assessed by a trained dermatologist. Forty women with mild-to-severe acne and 40 control subjects were included. A global linear model identified a significant negative correlation between the severity of acne and the adherence to the MD in acne patients (regression coefficient = −0.17; P = 0.017). This was the first study conducted in France to investigate the relationship between the adherence to the MD and the severity of facial acne in women. This study confirmed the importance of using a holistic approach for acne management. Further studies are needed to confirm our findings.

Today smartphones are inseparable parts of modern life and are capable of performing many desktop computers' tasks such as scientific analysis with greater convenience. Here, we present OligoCOOL, which is an Android application for analyzing nucleic sequences. This application enables users to perform several common biomedical analyses for a given nucleotide sequence. OligoCOOL is a freely accessible Android app at http://bioinf.modares.ac.ir/software/OligoCOOL, which can be a suitable tool for the experimental design in the laboratories. This application also can be used to learn the basics of nucleotide sequence analysis.

Acne is a chronic inflammatory skin condition that involves Cutibacterium acnes (C. acnes), which is classified into six main phylotypes (IA1, IA2, IB, IC, II and III). Acne development is associated with loss of C. acnes phylotype diversity, characterised by overgrowth of phylotype IA1 relative to other phylotypes. It was also shown that purified extracellular vesicles (EVs) secreted by C. acnes can induce an acne‐like inflammatory response in skin models. We aimed to determine if the inflammatory profile of EVs secreted by C. acnes phylotype IA1 from an inflammatory acne lesion was different from C. acnes phylotype IA1 from normal skin, thus playing a direct role in the severity of inflammation. EVs were produced in vitro after culture of two clinical strains of C. acnes phylotype IA1, T5 from normal human skin and A47 from an inflammatory acne lesion, and then incubated with either human immortalised keratinocytes, HaCaT cells, or skin explants obtained from abdominoplasty. Subsequently, quantitative PCR (qPCR) was performed for human β‐defensin 2 (hBD2), cathelicidin (LL‐37), interleukin (IL)‐1β, IL‐6, IL‐8, IL‐17α and IL‐36γ, and ELISA for IL‐6, IL‐8 and IL‐17α. We found that EVs produced in vitro by C. acnes derived from inflammatory acne lesions significantly increased the pro‐inflammatory cytokines and anti‐microbial peptides at both transcriptional and protein levels compared with EVs derived from normal human skin. We show for the first time that C. acnes EVs from inflammatory acne play a crucial role in acne‐associated inflammation in vitro and that C. acnes phylotype IA1 collected from inflammatory acne lesion and normal skin produce different EVs and inflammatory profiles in vitro. [ABSTRACT FROM AUTHOR]

Background and Objective: Air pollution is one of the most important environmental risk factors that exposure to it can cause many acute and chronic effects on human health. Some regions of Iran, especially the western, southern and southeastern provinces of the country, have been affected with dust storm for years. Studies on the frequencies of dusty days in the country show that central pits of Iran and the cities of Zabol and Zahedan have the highest incidence of dusty days. The purpose of this study was to determine the concentration of suspended particles with aerodynamic diameter of 2.5 μm or less (PM2.5) in various seasons and months during 2019 in Zahedan. Materials and Methods: In this descriptive-analytical and cross-sectional study samples were typically collected once every 6 days during a 24-hour period as well as on dusty days using an air sampler (PQ200 / BGI) from July 2018 to July 2019. Results: The results show that the mean concentration of PM2.5 in Zahedan during this study was 36.86 µg/m3. The maximum and minimum PM2.5 daily concentrations in the sampling days were also measured as 130.8 and 4.75 µg/m3, respectively. Conclusion: In conclusion, 88% of samples contained PM2.5 concentration above the WHO 24-hr air quality guideline level (25 µg/m3), which could be due to the high incidence of summer dust storms. This indicates that particulate matters are a serious health threat to people living in those areas and calls for the implementing measures to tackle the problem.