Articles de revues sur le sujet « Wu 49 o63 2002 »

Chinese herbal medicine (CHM) has been commonly used for treating insomnia in Asian countries for centuries. The aim of this study was to conduct a large-scale pharmaco-epidemiologic study and evaluate the frequency and patterns of CHM use in treating insomnia. We obtained the traditional Chinese medicine (TCM) outpatient claims from the National Health Insurance in Taiwan for the year 2002. Patients with insomnia were identified from the diagnostic code of International Classification of Disease among claimed visiting files. Corresponding prescription files were analyzed, and an association rule was applied to evaluate the co-prescription of CHM. Results showed that there were 16 134 subjects who visited TCM clinics for insomnia in Taiwan during 2002 and received a total of 29 801 CHM prescriptions. Subjects between 40 and 49 years of age comprised the largest number of those treated (25.3%). In addition, female subjects used CHMs for insomnia more frequently than male subjects (female : male = 1.94 : 1). There was an average of 4.8 items prescribed in the form of either an individual Chinese herb or formula in a single CHM prescription for insomnia. Shou-wu-teng (Polygonum multiflorum) was the most commonly prescribed single Chinese herb, while Suan-zao-ren-tang was the most commonly prescribed Chinese herbal formula. According to the association rule, the most commonly prescribed CHM drug combination was Suan-zao-ren-tang plus Long-dan-xie-gan-tang, while the most commonly prescribed triple drug combination was Suan-zao-ren-tang,Albizia julibrissin, andP. multiflorum. Nevertheless, further clinical trials are needed to evaluate the efficacy and safety of these CHMs for treating insomnia.

The genus Armillaria (2) and Armillaria mellea sensu lato (3) have been reported previously from Hawaii. However, Armillaria species in Hawaii have not been previously identified by DNA sequences, compatibility tests, or other methods that distinguish currently recognized taxa. In August 2005, Armillaria rhizomorphs and mycelial bark fans were collected from two locations on the island of Hawaii. Stands in which isolates were collected showed moderate to heavy tree mortality and mycelial bark fans. Pairing tests (4) to determine vegetative compatibility groups revealed three Armillaria genets (HI-1, HI-7, and HI-9). Rhizomorphs of genet HI-1 were collected from both dead and healthy mature trees of the native 'Ohia Lehua (Metrosideros polymorpha) approximately 27 km west of Hilo, HI (approximately 19°40′49″N, 155°19′24″W, elevation 1,450 m). Rhizomorphs of HI-7 and HI-9 were collected, respectively, from dead/declining, mature, introduced Nepalese alder (Alnus nepalensis) and from an apparently healthy, mature, introduced Chinese banyan (Ficus microcarpa) in the Waipi'o Valley (approximately 20°03′29″N, 155°37′35″W, elevation 925 m). On the basis of somatic pairing tests and intergenic spacer-1 (IGS-1) nucleotide sequence identities of 99 to 100% with North American A. nabsnona (GenBank Accession No. AY509178), HI-1 (GenBank Accession No. DQ995356), HI-7 (GenBank Accession No. DQ995358), and HI-9 (GenBank Accession No. DQ995359) were identified as A. nabsnona, a pathogen of hardwoods (1). The IGS-1 sequences of A. nabsnona genets (HI-1, HI-7, and HI-9) had a greater similarity to North American collections of A. nabsnona than to the Asian A. nabsnona, even though the two introduced hosts originated from Asia. Phylogeographic studies could help determine the potential introduction and original source of A. nabsnona in Hawaii. Although A. nabsona was isolated from multiple hosts in declining stands, pathogenicity studies are needed to confirm whether this pathogen causes disease on diverse native and exotic tree species in Hawaii. References: (1) E. Allen et al. Pages 2–7 in: Common Tree Diseases of British Columbia. Natural Resources Canada. Canadian Forest Service, Victoria, BC, Canada, 1998. (2) D. E. Hemmes and D. E. Desjardin. Pages 129 and 153 in: Mushrooms of Hawaii. Ten Speed Press, Berkeley, CA, 2002. (3) F. F. Laemmlen and R. V. Bega. Plant Dis. Rep. 58:102, 1974. (4) Y. Wu et al. USDA Forest Service Tech. Rep. R2-58, 1996.

We present a surface plasmon resonance (SPR) structure based on Kretschmann configuration incorporating bimetallic layers of noble (Ag) and magnetic materials (Ni) over CaF2 prism. Extensive numerical analysis based on transfer matrix theory has been performed to characterize the sensor response considering sensitivity, full width at half maxima, and minimum reflection. Notably, the proposed structure, upon suitably optimizing the thickness of bimetallic layer provides consistent enhancement of sensitivity over other competitive SPR structures. Hence we believe that this proposed SPR sensor could find the new platform for the medical diagnosis, chemical examination and biological detection. Full Text: PDF ReferencesJ. Homola, S.S. Yee, G. Gauglitz, "Surface plasmon resonance sensor based on planar light pipe: theoretical optimization analysis", Sens. Actuators B Chem. 54, 3 (1999). CrossRef X.D. Hoa, A.G. Kirk, M. 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Abstract Background: Between 54%-85% of pediatric patients (pts) with ALL can be cured by definitive chemotherapy protocols. HSCT may be considered for high-risk pts after induction therapy or for refractory/relapsed pts. However, HSCT is recognized as a highly specialized, costly and resource intensive procedure requiring ongoing care over months to years. HSCT is associated with significant life-threatening complications with transplant related mortality of 20-30% and acute/chronic graft vs. host disease and infections. The objective of this study was to assess the economic burden up to 5 years of pediatric pts with ALL who received HSCT from the US commercial payers' perspective. Method: Pediatric pts (<18 years old) with ALL (ICD-9 CM codes 204.0x) who underwent an allogeneic HSCT ([ICD-9 CM] procedure codes 41.02, 41.03, 41.05, 41.06, 41.08) in the US (2002-2013) were identified from two large administrative claims databases. Selected pts were continuously enrolled in their healthcare plan for ≥6 months before and ≥1 month after the index date (i.e., the date the first HSCT procedure was recorded). Age and gender as of the index date and total healthcare costs (direct medical costs and pharmacy costs) during the 6 months preceding the index date were reported. The economic burden associated with HSCT was described by assessing the healthcare resource utilization (HRU) and costs over the following study periods: between the index date and the HSCT hospitalization discharge date, during the first 100 days following the index date, and, during the first, second, third, fourth and fifth years following the index date. For each period, the analyses were conducted among pts with continuous healthcare plan enrollment for that entire period. Healthcare costs reported reflect the costs reimbursed by US private payers for a pediatric pt with ALL who underwent HSCT. Costs were adjusted for inflation (based on the consumer price index for medical components) and reported as 2014 US dollars (USD). Results: A total of 209 pediatric ALL pts were identified. Mean age was 10 years and 43.1% of pts were female. The median follow-up period after the index date was 1.3 years. During the 6 months prior to the index date, pts incurred average total healthcare costs of $287,001. The median duration of the initial hospitalization for the HSCT was 41 days (interquartile range 32-55). Over the five years following the index date, results showed substantial HRU and costs associated with the HSCT. The most intensive HRU and highest healthcare costs were observed within the first year following the index date; pts had an average of 49 days with outpatient (OP) visits, 29 days with OP laboratory services, and 68 inpatient (IP) days corresponding to 3.10 IP admissions (including the hospitalization for the first HSCT) and incurred mean total healthcare costs of $683,099 (median of $511,021) (Figure 1 and 2). Costs associated with the first HSCT hospitalization represented 62.4% of the total costs incurred during the first year. Although a decreasing trend was observed over time, HRU and costs remained high; 28.8% of pts had at least one IP admission at year 2, 19.6% at year 3, 20.0% at year 4, and 6.7% at year 5 (Figure 1). The number of days with OP visits and the number of days with laboratory services also remained high over time (Figure 1). The average total healthcare cost was $104,584 (median of $21,877) at year 2, $79,092 (median of $11,000) at year 3, $106,334 (median of $10,426) at year 4 and, and $38,291 (median of $10,082) at year 5 (Figure 2). Our results also showed high variation in healthcare costs across pediatric pts following the index date; 29.4% of the total costs (over the entire sample) in year 1 were incurred by the 10% pts with the highest costs. Starting from the second year, the 10% of pts with the highest costs accounted for 61.3 to 76.6% of the total costs for each year, suggesting that a small proportion of pts still incur very high costs several years after HSCT. Conclusions: Healthcare resource utilization and direct costs associated with allogeneic HSCT are substantial with the first year direct cost alone of $683,099 with substantial costs over the following years. Further studies are needed to understand the humanistic and financial burden of HSCT for pediatric pts and their caregivers. Figure 1. HRU after Index Date Figure 1. HRU after Index Date Figure 2. Total Healthcare Costs after Index Date Figure 2. Total Healthcare Costs after Index Date Disclosures Maziarz: Athersys: Consultancy, Patents & Royalties, Research Funding; Novartis: Consultancy. Guerin:GlaxoSmithKline, Janssen Scientific Affairs, Janssen-Ortho, Inc., Merck & Co., Inc., Merck Frosst Canada, Novartis Pharmaceuticals Corporation, Novo Nordisk Inc., Ogilvy Renault, Ortho-Clinical Diagnostics, Inc., Otsuka America Pharmaceutical, Inc.,: Consultancy, Other: Annie Guerin is an employee of Analysis Group Inc, which has received consultancy fees from the listed organizations; Pfizer Canada, Inc., RX&D, Sanofi, Savient Pharmaceuticals, Inc., Shire Pharmaceuticals Inc., Sunovion Pharmaceuticals Inc., Takeda Global Research & Development Center, Inc., Takeda Pharmaceuticals U.S.A., Inc.: Consultancy, Other: Annie Guerin is an employee of Analysis Group Inc, which has received consultancy fees from the listed organizations; AbbVie Inc., Alcon Laboratories, Bayer Healthcare Pharmaceuticals, LLC, Celgene Corporation, Cempra Inc., Centocor Ortho Biotech, Cooley LLP, Cyberonics, Inc., DLA Piper, Eli Lilly & Company,Forest Laboratories, Inc., Genentech, Inc.,: Consultancy, Other: Annie Guerin is an employee of Analysis Group Inc, which has received consultancy fees from the listed organizations. Gauthier:AbbVie Inc., Celgene Corporation, Eli Lilly & Company, Genentech, Inc. ,GlaxoSmithKline, Janssen Scientific Affairs, LLC, Novartis Pharmaceuticals Corporation, Pfizer Canada, Inc., Sanofi, Savient Pharmaceuticals, Inc., Shire Pharmaceuticals Inc.,: Consultancy, Other: Genevieve Gauthier is an employee of Analysis Group Inc, which has received consultancy fees from the listed organizations; Sunovion Pharmaceuticals Inc.,Takeda Pharmaceuticals U.S.A., Inc.: Consultancy, Other: Genevieve Gauthier is an employee of Analysis Group Inc, which has received consultancy fees from the listed organizations. Heroux:AbbVie Inc., Alcon Laboratories, Celgene Corporation, Genentech, Inc., Merck Frosst Canada, Novartis Pharmaceuticals Corporation, Shire Pharmaceuticals Inc., Sunovion Pharmaceuticals Inc., Takeda Pharmaceuticals U.S.A., Inc.: Consultancy, Other: Julie Heroux is an employee of Analysis Group Inc, which has received consultancy fees from the listed organizations. Zhdanava:AbbVie Inc., Genentech, Inc., Merck Frosst Canada, Novartis Pharmaceuticals Corporation,Shire Pharmaceuticals Inc., Takeda Pharmaceuticals U.S.A., Inc.: Consultancy, Other: Maryia Zhdanava is an employee of Analysis Group Inc, which has received consultancy fees from the listed organizations. Wu:Molecular Insight Pharmaceuticals, Inc., Novartis Pharmaceuticals Corporation, Ortho McNeil Pharmaceuticals, Inc., Sanofi, Savient Pharmaceuticals, Inc., Shire Pharmaceuticals Inc.,: Consultancy, Other: Eric Q Wu is an employee of Analysis Group Inc, which has received consultancy fees from the listed organizations; Takeda Global Research & Development Center, Inc., Takeda Pharmaceuticals U.S.A., Inc., TAP Pharmaceutical Products, Inc., Vertex Pharmaceuticals Incorporated: Consultancy, Other: Eric Q Wu is an employee of Analysis Group Inc, which has received consultancy fees from the listed organizations; Janssen Pharmaceutica, Inc., Janssen Scientific Affairs, LLC, Lilly Research Laboratories, McNeil Consumer & Specialty Pharmaceuticals, MedImmune, LLC, Melinta Therapeutics, Inc., Millennium Pharmaceuticals, Inc.,: Consultancy, Other: Eric Q Wu is an employee of Analysis Group Inc, which has received consultancy fees from the listed organizations; Celgene Corporation, Centocor Ortho Biotech, Cephalon, Inc., ConvaTec Inc., Corus Pharma, Inc., Eli Lilly & Company, Eli Lilly & Company, Ethicon, Inc., Forest Laboratories, Inc., Genentech, Inc., GlaxoSmithKline, Janssen Global Services, LLC,: Consultancy, Other: Eric Q Wu is an employee of Analysis Group Inc, which has received consultancy fees from the listed organizations; AbbVie Inc., Alcon Laboratory, Astellas Pharma Inc., Astellas Pharma US, Inc., AstraZeneca, Barger & Wolen LLP, Bayer Healthcare Pharmaceuticals, LLC, Biosense Webster, Inc., Blue Cross Blue Shield Association, Boehringer Ingelheim, Bristol-Myers Squibb C: Consultancy, Other: Eric Q Wu is an employee of Analysis Group Inc, which has received consultancy fees from the listed organizations. Thomas:Novartis: Employment. Chen:Novartis Pharmaceuticals Corporation: Employment, Equity Ownership, Other: Lei Chen is an employee of and owns stocks/options of Novartis Pharmaceuticals Corporation, the sponsor of this study.

Background:N-terminal pro-brain-type natriuretic peptide (NT-proBNP) and troponin I (TnI) are established cardiac biomarkers that predict cardiovascular events (CVEs) in the general population. While patients with psoriatic arthritis and psoriasis, collectively termed psoriatic disease (PsD), have an increased risk of developing CVEs, the use of these cardiac biomarkers to predict CV risk has not been investigated in this population.Objectives:We aimed to evaluate the association between these cardiac biomarkers and incident CVEs, and assess their predictive value beyond the Framingham Risk Score (FRS).Methods:A longitudinal cohort study was conducted in patients with PsD without prior history of CVEs. NT-proBNP and TnI concentrations were measured using automated clinical assays in the first available serum sample. The study outcome included any of the following CVEs occurring within the first 10 years of biomarker assessment: angina, myocardial infarction, transient ischemic attack, stroke, revascularization and CV death. Associations with incident CVEs were analyzed separately for each biomarker using Cox proportional hazards regression models first adjusted for age and sex, and subsequently for the FRS. The added value of cardiac biomarkers to improve predictive performance beyond the FRS was assessed using the area under the receiver operator characteristic curve (AUC), net reclassification index (NRI) and integrated discrimination index (IDI).Results:A total of 1000 patients with PsD were assessed between 2002 and 2019 (mean age 49 ± 12.8 years, 44.6% female) (Table 1). During a mean follow-up of 7.1 years, 64 patients developed incident CVEs. Both TnI (Hazard Ratio (HR) 3.02, 95% Confidence Interval (CI) 1.12, 8.16) and NT-proBNP (HR 2.02; 95% CI 1.28, 3.18) predicted CVEs independently of the FRS (Figure 1). The association was stronger in males than females. Including all cardiac biomarkers and the FRS in a single model, NT-proBNP retained statistical significance (HR 1.91, 95% CI 1.23, 2.97), while TnI did not (HR 2.60, 95% CI 0.98, 6.87). When comparing the predictive performance of the base model (FRS alone, AUC 75.4) to the expanded models, there was no significant improvement in any of the predictive indices with the addition of TnI (AUC 73.5, p = 0.21; NRI 0.08, p = 0.67; IDI 0.005, p = 0.37), NT-proBNP (AUC 71.0, p = 0.35; NRI 0.20, p = 0.06; IDI 0.017, p = 0.10), or both TnI and NT-proBNP (AUC 70.0, p = 0.23; NRI 0.27, p = 0.05; IDI 0.021, p =0.05).Conclusion:In patients with PsD, elevated NT-proBNP and TnI predict incident CVEs independent of the FRS. We did not observe a significant improvement in the performance of the predictive model when combining these cardiac biomarkers with the FRS.References:[1]Eder L, Wu Y, Chandran V, et al. Incidence and predictors for cardiovascular events in patients with psoriatic arthritis. Ann Rheum Dis 2016;75(9):1680-6.Table 1.Baseline characteristics of the study population (n=1000)VariableMean ± SD / Frequency (%)PsA, no. (%)648 (64.8)PsC, no. (%)352 (35.2)Age (years)49 ± 12.8Male sex, no. (%)554 (55.4)Disease duration (years)20.2 ± 14.1Ethnicity, Caucasian (%)834 (83.4)Current smoker (%)164 (16.4)FRS (%)8.2 ± 8.6Diabetes77 (7.7)Hypertension274 (27.4)BMI (kg/m2)28.7 ± 5.9PASI4.1 ± 6.3Use of lipid-lowering medications (%)100 (10)Current use of DMARDs362 (36.2)Current use of Biologics214 (21.4)Current use of NSAIDs (daily use)265 (26.5)1 Applicable only to patients with PsA CVE, cardiovascular events; DMARD, disease-modifying antirheumatic drug; FRS, Framingham Risk Score; NSAID, non-steroidal anti-inflammatory drug; PASI, Psoriasis Area Severity Index; PsA, psoriatic arthritis; PsC, psoriasis without arthritisFigure 1.Hazard ratios of cardiac biomarker measures for incident cardiovascular events (n = 1000, 64 events). Error bars denote 95% confidence intervals. CI indicates confidence interval; CVEs, cardiovascular events; FRS, Framingham Risk Score; NT-proBNP, N-terminal pro-brain-type natriuretic peptide; TnI, troponin I.Acknowledgements:Keith Colaco is supported by the Enid Walker Estate, Women’s College Research Institute, Arthritis Society (TGP-19-0446), National Psoriasis Foundation (Early Career Grant) and the Edward Dunlop Foundation. Lihi Eder is supported by a Young Investigator Award from the Arthritis Society and an Early Researcher Award from the Ontario Ministry of Science and Innovation. The study was supported in part by a discovery grant from the National Psoriasis Foundation and an operating grant from the Arthritis Society (YIO-16-394).Disclosure of Interests:None declared.

Abstract Abstract 4274 Background: While iron overload is known to cause hepatic toxicity, the effect of iron chelation therapy on liver pathology is not well understood. Data evaluating liver fibrosis during iron chelation therapy are limited to small studies (eg, Wu SF et al. Hemoglobin 2006 [n=17], Berdoukas V et al. Hematol J 2005 [n=49], Wanless IR et al. Blood 2002 [n=56]). In order to address such effects in a more robust patient population, we assessed liver biopsy samples from β-thalassemia patients enrolled in two large clinical studies (Porter J et al. Blood 2005, Cappellini MD et al. Blood 2006) that evaluated the effects of deferasirox on iron burden for up to 5 years. Methods: Patients with β-thalassemia and transfusional hemosiderosis receiving ≥8 blood transfusions/year, with liver biopsy assessment (defined as having either liver iron concentration [LIC], Ishak grading or Ishak staging assessment), after at least 3 years of deferasirox treatment, were included. Deferasirox dose was 5–40 mg/kg/day based upon level of iron overload (Study 107, patients randomized to deferoxamine [DFO] or deferasirox for the first year; Study 108, patients received deferasirox only). Treatment response success was defined according to baseline (start of deferasirox dosing) and end-of-study (EOS) LIC measurements (Table). Histological total iron score (TIS) was derived from the iron load observed in hepatocytes (hepatocytic iron score [HIS] range, 0–12), sinusoidal cells (sinusoidal iron score [SIS] range, 0–4) and main structures of the portal tracts (portal iron score [PIS]). A heterogeneity factor (H = 1, 2 or 3) was then applied, based on the overall appearance of the tissue, to provide TIS, calculated as (HIS + SIS + PIS) × (H/3) [range 0–60]. Hepatocytic to total liver iron ratio was calculated as HIS/(HIS + SIS + PIS) (Deugnier Y et al. Gastroenterol 1992). Fibrosis staging was performed according to Ishak scale from 0 (no fibrosis) to 6 (cirrhosis, probable or definite). Liver inflammation was assessed according to the Ishak necroinflammatory grading system with an overall scoring range from 0–18 (Ishak K et al. J Hepatology 1995). Results: Of 770 patients enrolled in the deferasirox studies, 219 with histological biopsy data at baseline and at the end of at least 3 years of treatment with deferasirox were eligible for analyses. Mean LIC was 15.7 ± 9.9 mg Fe/g dw and median serum ferritin was 2069 ng/mL (range 273–11698) at the start of deferasirox treatment. After at least 3 years of treatment, overall LIC success response rate was 63.8% (n=134), and mean LIC decreased by 5.5 ± 10.6 to 10.1 ± 8.2 mg Fe/g dw. Mean absolute change in TIS and liver iron ratio were -8.2 ± 13.3 and -2.1 ± 27.3, respectively. The range of Ishak necroinflammatory scores at baseline was 0–8 with a mean of 2.0 (2.2 in patients who met success rate criteria [Group A], 1.6 in patients who did not meet the success rate criteria [Group B]). At EOS the necroinflammatory score improved to a mean of 0.8 overall, and in both subgroups, with a mean relative change of -66% (69% in Group A and -61% in Group B). Overall 83.3% (n=175) [85.8% (n=115) in Group A, 78.9% (n=60) in Group B] of patients experienced either stabilization or improvement in their Ishak fibrosis score. Ishak staging remained stable (change of -1, 0 or +1) in 55.7% (n=122) of patients. Fifty-nine patients (26.9%) had an improvement in Ishak grading by a score of ≥2. Similar improvements were observed between Group A (26.1%, n=35) and Group B (30.3%, n=23). Conclusions: This is the first study to assess the effect of iron chelation therapy on liver pathology in a large cohort of iron-overloaded patients with β-thalassemia. In addition to reducing total iron burden, deferasirox led to an improvement in pathological markers of iron overload-induced liver damage in the majority of patients; 83.3% showed stabilization or improvement in Ishak fibrosis staging as well as an overall improvement in necroinflammatory score. These effects were similar in both patients who met the LIC success rate criteria and those who did not, suggesting that the observed effects may be at least partly independent of the drug's chelation effect. These findings are important as stabilization or regression of hepatic fibrosis in the face of chronic insult may prevent progressive liver disease. Disclosures: Deugnier: Novartis: Honoraria. Dong:Novartis: Employment. Giannone:Novartis: Employment. Zhang:Novartis: Employment. Griffel:Novartis: Employment. Brissot:Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau.

Strawberry is one of the beloved fruits worldwide due to its exquisite flavor with highly nutritious compounds which give promising health benefits. [1] With dragging the great attention, efforts to monitor the quality of strawberries and strawberry derivatives are becoming significant to obtain better flavor and nutrition. 2,5-Dimethyl-4-hydroxy-3(2H)-furanone(furaneol) is one of the compounds which plays an important role in a flavor that can be naturally found in various fruits such as strawberry, pineapple, raspberry, and mango. Especially, furaneol composition is reported as a significant factor for maturity condition monitoring of strawberries due to the different amounts at the ripening stage. [2] Furaneol is also known to be an essential signature for controlling the food production process, verifying the food production origin, and regulating the quality of products. Currently, furaneol detection is conducted with time-consuming techniques, such as gas chromatography (GC) and high-performance liquid chromatography (HPLC). For example, Yuan et al. [3] showed the identification of furaneol with HPLC. Also, Buttery et al. [4], and Lopez et al. [5], used GC for the determination of furaneol in foods. Developing a real-time gas sensor for fast, cheap, stable, sensitive detection of furaneol is a significant challenge in the area of the food industry. Chemo-resistive gas sensors can be an attractive approach due to their miniaturization, simple operation, ease of fabrication, and low production cost. For utilizing resistive gas sensors, polyaniline (PANI) got great attention because of its environmental stability, simple synthesis, and ease of tailoring the surface charge characteristics by changing the dopants. However, PANI-based gas sensors are reactive to numerous gases which limits the selective detection of target gas molecules. Many compounds in strawberries may restrict the use of PANI-based sensors. [6] Molecular imprinting technology (MIT), which can create molecularly imprinted polymers (MIPs) obtaining specific binding sites for target molecules, is utilized to achieve selective gas sensing similar to biological antibodies. [7] The improved affinity not only provides selective detection but also enhances response to target gas molecules. In this study, a resistive gas sensor based on synthesized molecularly imprinted polymer and polyaniline is demonstrated for the detection of furaneol gas molecules for its operation in food packaging. Herein, we developed a unique method to synthesize molecularly imprinted polymer and polyaniline (MIP-PANI) nanocomposites with an interfacial polymerization technique. Aniline monomer is polymerized and oxidized simultaneously to tailor the surface charge characteristics forming polyaniline. Then, the molecularly imprinting process on polyaniline is conducted with methacrylic acid (MAA) as a functional monomer, ethylene glycol dimethacrylate (EGDMA) as a crosslinker, furaneol as a template, and benzoyl peroxide as a radical initiator. After the furaneol template was constructed, MIP-PANI presented a high affinity to furaneol target molecules and showed a high sensing response. Their response signals are enhanced tens of times compared to the pure PANI. Furthermore, selective detection of the target furaneol molecules was observed. This study may broaden the application of resistive gas sensors for selective and sensitive detection of volatile organic compounds in food industries. Reference [1] S. Afrin, M. Gasparrini, T.Y. Forbes-Hernandez, P. Reboredo-Rodriguez, B. Mezzetti, A. Varela-Lopez, F. Giampieri, M. Battino, Promising Health Benefits of the Strawberry: A Focus on Clinical Studies, J Agric Food Chem 64 (2016) 4435-4449. [2] C. Aubert, S. Baumann, H. Arguel, Optimization of the analysis of flavor volatile compounds by liquid-liquid microextraction (LLME). Application to the aroma analysis of melons, peaches, grapes, strawberries, and tomatoes, Journal of Agricultural and Food Chemistry 53 (2005) 8881-8895. [3] J.P. Yuan, F. Chen, Separation and identification of furanic compounds in fruit juices and drinks by high-performance liquid chromatography photodiode array detection, Journal of Agricultural and Food Chemistry 46 (1998) 1286-1291. [4] R.G. Buttery, G.R. Takeoka, M. Naim, H. Rabinowitch, Y. Nam, Analysis of furaneol in tomato using dynamic headspace sampling with sodium sulfate, Journal of Agricultural and Food Chemistry 49 (2001) 4349-4351. [5] R. Lopez, M. Aznar, J. Cacho, V. Ferreira, Determination of minor and trace volatile compounds in wine by solid-phase extraction and gas chromatography with mass spectrometric detection, Journal of Chromatography A 966 (2002) 167-177. [6] A.T. Oz, G. Baktemur, S.P. Kargi, E. Kafkas, Volatile Compounds of Strawberry Varieties, Chemistry of Natural Compounds 52 (2016) 507-509. [7] L. Chen, X. Wang, W. Lu, X. Wu, J. Li, Molecular imprinting: perspectives and applications, Chem Soc Rev 45 (2016) 2137-2211.

The paper presents research findings with 56 Roma children from Macedonia and Serbia between the ages of 3-6 years. The children’s knowledge of Romani as their mother tongue was assessed with a specially designed test. The test measures the children’s comprehension and production of different types of grammatical knowledge such as wh–questions, wh-complements, passive verbs, possessives, tense, aspect, the ability of the children to learn new nouns and new adjectives, and repetition of sentences. In addition, two pictured narratives about Theory of Mind were given to the children. The hypothesis of the authors was that knowledge of the complex grammatical categories by children will help them to understand better the Theory of Mind stories. The results show that Roma children by the age of 5 know most of the grammatical categories in their mother tongue and most of them understand Theory of Mind. References Bakalar, P. (2004). The IQ of Gypsies in Central Europe. 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Arsenic and Protein Expression: It might help to know the mechanism of As toxicity is described Introduction One of the largest public health problems at present is the drinking of water containing levels of Inorg-As that are known to be carcinogenic. The chronic ingestion of Inorg-As can results in skin cancer, urinary bladder cancer, lungs cancer, kidneys cancer, liver cancer, and cancer of other human organs 1-6. The molecular mechanisms of the carcinogenicity and toxicity of inorganic arsenic are not well understood 7–9. Many mechanisms of arsenic toxicity and carcinogenicity have been suggested 1, 7, 10 including chromosome abnormalities 11, oxidative stress 12, 13, altered growth factors 14, cell proliferation 15, altered DNA repair 16, altered DNA methylation patterns 17, inhibition of several key enzymes 18, gene amplification 19 etc. Some of these mechanisms result in alterations in protein expression. Proteomics is a powerful tool developed to enhance the study of complex biological system 20. This technique has been extensively employed to investigate the proteome response of cells to drugs and other diseases 21, 22. A proteome analysis of the Na-As (III) response in cultured lung cells found in vitro oxidative stress-induced apoptosis 23. In one of the study, hamsters were exposed to sodium arsenite (173 mg As/L) in drinking water for 6 days and several protein spots were over expressed and several were under expressed in the livers and urinary bladders of hamsters (Fig.) 24, 25. Hamsters were exposed to sodium arsenite (173 mg As/L) in drinking water for 6 days. The control hamsters were given tap water. The spot pairs of (A) equally expressed, (B) overexpressed, and (C) under expressed proteins in the liver tissues were shown. The amount of the protein is proportional to the volume of the protein peak. Transgelin was down-regulated, and GST-pi was up-regulated in the urinary bladder tissues of hamsters. In the liver tissues ornithine aminotransferase (OAT) was up-regulated, and senescence marker protein 30 (SMP 30), and fatty acid binding protein (FABP) were down-regulated. Down-regulation of transgelin has been noted in the urinary bladders of rats having bladder outlet obstruction 26. Ras-dependent and Ras-independent mechanisms can cause the down regulation of transgelin in human breast and colon carcinoma cell lines and patient-derived tumor samples 27. The loss of transgelin expression has been found in prostate cancer cells 28 and in human colonic neoplasms 29. It has been suggested that the loss of transgelin expression may be an important early event in tumor progression and a diagnostic marker for cancer development 26-29. Figure. Three-dimentional simulation of over-and under expressed protein spots in the livers of hamsters using Decyder software. Over-expression of GST-pi has been found in colon cancer tissues 30. Strong expression of GST-pi also has been found in gastric cancer 31, malignant melanoma 32, lung cancer 33, breast cancer 34 and a range of other human tumors 35. GST-pi has been up-regulated in transitional cell carcinoma of human urinary bladder 36. OAT has a role in regulating mitotic cell division and it is required for proper spindle assembly in human cancer cell 37. Ornithine amino transferase knockdown in human cervical carcinoma and osteosarcoma cells by RNA interference blocks cell division and causes cell death 37. It has been suggested that ornithine amino transferase has a role in regulating mitotic cell division and it is required for proper spindle assembly in human cancer cells 37. SMP 30 expressed mostly in the liver. By stimulating membrane calcium-pump activity it protects cells against various injuries 38. High levels of saturated, branched chain fatty acids are deleterious to cells and resulting in lipid accumulation and cytotoxicity. FABP expression has protected the cells against branched chain saturated fatty acid 39. Proteomics would be a powerful tool to know the unknown cellular mechanisms of arsenic toxicity in humans. References. NRC (National Research Council). (2001). Arsenic in Drinking Water. Update to the 1999 Arsenic in Drinking Water Report. National Academy Press, Washington, DC. Chen, C. J., Chen, C. , Wu, M. M., Kuo, T. L. (1992). Cancer potential in liver, lung, bladder, and kidney due to ingested inorganic arsenic in drinking water. Br. J. Cancer 66, 888-892. Hopenhayn-Rich, C., M.L. Biggs, A. Fuchs, et al. 1996. Bladder cancer mortality with arsenic in drinking water in Argentina. Epidemiology 7: 117–124. International Agency for Research on Cancer. (1987). In IARC Monograph on the Evaluation of Carcinogenicity Risk to Humans. 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R., Carcinogenicity and co-carcinogenicity of sodium arsenite in p53+/- male mice. Toxicologist 2000, 54, 134. Li, J. H., Rossman, T. G., Mechanism of co-mutagenesis of sodium arsenite with N-methyl-N-nitrosourea. Bi Trace Elem. 1989, 21, 373-381. Zhao, C. Q., Young, M. R., Diwan, B. A., Coogan, T. P., et , Association of arsenic-induced malignant transformation with DNA hypomethylation and aberrant gene expression. Proc. Natl. Acad. Sci. USA 1997, 94, 10907-10912. Abernathy, C. O., Lui, Y. P., Longfellow, D., Aposhian, H. , et al., Arsenic: Health effects, mechanisms of actions and research issues. Environ. Health Perspect. 1999, 107, 593-597. Lee, T. C., Tanaka, N., Lamb, P. W., Gilmer, T. M., et al., Induction of gene amplification by arsenic. Science 1988, 241, 79-81. Lau, A. T., He, Q. Y., Chiu, J. F. (2003). Proteomic technology and its biomedical applications. Acta Biochim. Bioph Sin. 35, 965-975. Jungblut, P. 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Our studies have indicated that the relative concentration of Se or Hg to As in urine and blood positively correlates with percentage of inorganic arsenic (% Inorg-As) and percentage of monomethlyarsonic acid [% MMA (V)]. We also found a negative correlation with percentage of dimethylarsinic acid [% DMA (V)] and the ratio of % DMA (V) to % MMA (V). In another study, we found that a group of proteins were significantly over expressed and conversely other groups were under-expressed in tissues in Na-As (III) treated hamsters. Introduction.Inorganic arsenic (Inorg-As) in drinking water.One of the largest public health problems at present is the drinking of water containing levels of Inorg-As that are known to be carcinogenic. At least 200 million people globally are at risk of dying because of arsenic (As) in their drinking water1-3. The chronic ingestion of Inorg-As can results in skin cancer, bladder cancer, lung cancer, and cancer of other organs1-3. The maximum contamination level (MCL) of U.S. drinking water for arsenic is 10 ug/L. The arsenic related public health problem in the U.S. is not at present anywhere near that of India4, Bangladesh4, and other countries5. Metabolism and toxicity of Inorg-As and arsenic species.Inorg-As is metabolized in the body by alternating reduction of pentavalent arsenic to trivalent form by enzymes and addition of a methyl group from S-adenosylmethionine6, 7; it is excreted mainly in urine as DMA (V)8. Inorganic arsenate [Inorg-As (V)]is biotransformed to Inorg-As (III), MMA (V), MMA (III), DMA (V), and DMA (III)6(Fig. 1). Therefore, the study of the toxicology of Inorg-As (V) involves at least these six chemical forms of arsenic. Studies reported the presence of 3+ oxidation state arsenic biotransformants [MMA (III) and DMA (III)] in human urine9and in animal tissues10. The MMA (III) and DMA (III) are more toxic than other arsenicals11, 12. In particular MMA (III) is highly toxic11, 12. In increased % MMA in urine has been recognized in arsenic toxicity13. In addition, people with a small % MMA in urine show less retention of arsenic14. Thus, the higher prevalence of toxic effects with increased % MMA in urine could be attributed to the presence of toxic MMA (III) in the tissue. Previous studies also indicated that males are more susceptible to the As related skin effects than females13, 15. A study in the U.S population reported that females excreted a lower % Inorg-As as well as % MMA, and a higher % DMA than did males16. Abbreviation: SAM, S-adenosyl-L-methionine; SAHC, S-adenosyl-L-homocysteine. Differences in susceptibility to arsenic toxicity might be manifested by differences in arsenic metabolism among people. Several factors (for examples, genetic factors, sex, duration and dosage of exposure, nutritional and dietary factors, etc.) could be influence for biotransformation of Inorg-As,6, 17 and other unknown factors may also be involved. The interaction between As, Se, and Hg.The toxicity of one metal or metalloid can be dramatically modulated by the interaction with other toxic and essential elements18. Arsenic and Hg are toxic elements, and Se is required to maintain good health19. But Se is also toxic at high levels20. Recent reports point out the increased risk of squamous cell carcinoma and non-melanoma skin cancer in those treated with 200 ug/day of selenium (Nutritional Prevention of Cancer Trial in the United States)21. However, it is well known that As and Se as well as Se and Hg act as antagonists22. It was also reported that Inorg-As (III) influenced the interaction between selenite and methyl mercury23. A possible molecular link between As, Se, and Hg has been proposed by Korbas et al. (2008)24. The identifying complexes between the interaction of As and Se, Se and Hg as well as As, Se, and Hg in blood of rabbit are shown in Table 1. Influence of Se and Hg on the metabolism of Inorg-As.The studies have reported that Se supplementation decreased the As-induced toxicity25, 26. The concentrations of urinary Se expressed as ug/L were negatively correlated with urinary % Inorg-As and positively correlated with % DMA27. The study did not address the urinary creatinine adjustment27. Other researchers suggested that Se and Hg decreased As methylation28-31(Table 2). They also suggested that the synthesis of DMA from MMA might be more susceptible to inhibition by Se (IV)29 as well as by Hg (II)30,31 compared to the production of MMA from Inorg-As (III). The inhibitory effects of Se and Hg were concentration dependent28-31. The literature suggests that reduced methylation capacity with increased % MMA (V), decreased % DMA (V), or decreased ratios of % DMA to % MMA in urine is positively associated with various lesions32. Lesions include skin cancer and bladder cancer32. The results were obtained from inorganic arsenic exposed subjects32. Our concern involves the combination of low arsenic (As) and high selenium (Se) ingestion. This can inhibit methylation of arsenic to take it to a toxic level in the tissue. Dietary sources of Se and Hg.Global selenium (Se) source are vegetables in the diet. In the United States, meat and bread are the common source. Selenium deficiency in the US is rare. The US Food and Drug Administration (FDA) has found toxic levels of Se in dietary supplements, up to 200 times greater than the amount stated on the label33. The samples contained up to 40,800 ug Se per recommended serving. For the general population, the most important pathway of exposure to mercury (Hg) is ingestion of methyl mercury in foods. Fish (including tuna, a food commonly eaten by children), other seafood, and marine mammals contain the highest concentrations. The FDA has set a maximum permissible level of 1 ppm of methyl mercury in the seafood34. The people also exposed mercury via amalgams35. Proteomic study of Inorg-As (III) injury.Proteomics is a powerful tool developed to enhance the study of complex biological system36. This technique has been extensively employed to investigate the proteome response of cells to drugs and other diseases37, 38. A proteome analysis of the Na-As (III) response in cultured lung cells found in vitro oxidative stress-induced apoptosis39. However, to our knowledge, no in vivo proteomic study of Inorg-As (III) has yet been conducted to improve our understanding of the cellular proteome response to Inorg-As (III) except our preliminary study 40. Preliminary Studies: Results and DiscussionThe existing data (Fig. 1) from our laboratory and others show the complex nature of Inorg-As metabolism. For many years, the major way to study, arsenic (As) metabolism was to measure InorgAs (V), Inorg-As (III), MMA (V), and DMA (V) in urine of people chronically exposed to As in their drinking water. Our investigations demonstrated for the first time that MMA (III) and DMA (III) are found in human urine9. Also we have identified MMA (III) and DMA (III) in the tissues of mice and hamsters exposed to sodium arsenate [Na-As (V)]10, 41. Influence of Se as well as Hg on the As methyltransferase.We have reported that Se (IV) as well as mercuric chloride (HgCl2) inhibited As (III) methyltransferase and MMA (III) methyltransferase in rabbit liver cytosol. Mercuric chloride was found to be a more potent inhibitor of MMA (III) methyltransferase than As (III) methyltransferase30. These results suggested that Se and Hg decreased arsenic methylation. The inhibitory effects of Se and Hg were concentration dependent30. Influence of Se and Hg in urine and blood on the percentage of urinary As metabolites.Our human studies indicated that the ratios of the concentrations of Se or Hg to As in urine and blood were positively correlated with % Inorg-As and % MMA (V). But it negatively correlated with % DMA (V) and the ratios of % DMA (V) to % MMA (V) in urine of both males and females (unpublished data) (Table 3). These results confirmed that the inhibitory effects of Se as well as Hg for the methylation of Inorg-As in humans were concentration dependent. We also found that the concentrations of Se and Hg were negatively correlated with % Inorg-As and % MMA (V). Conversely it correlated positively with % DMA (V) and the ratios of % DMA (V) to % MMA (V) in urine of both sexes (unpublished data). These correlations were not statistically significant when urinary concentrations of Se and Hg were adjusted for urinary creatinine (Table 3). Interactions of As, Se, Hg and its relationship with methylation of arsenic are summarized in Figure 2. Sex difference distribution of arsenic species in urine.Our results indicate that females have more methylation capacity of arsenic as compared to males. In our human studies (n= 191) in Mexico, we found that females (n= 98) had lower % MMA (p<0.001) and higher % DMA (p=0.006) when compared to males (n= 93) (Fig. 3). The means ratio of % MMA (V) to % Inorg-As and % DMA (V) to %MMA (V) were also lower (p<0.05) and higher (p<0.001), respectively in females compared to males. The protein expression profiles in the tissues of hamsters exposed to Na-As (III).In our preliminary studies40, hamsters were exposed to Na-As (III) (173 pg/ml as As) in their drinking water for 6 days and control hamsters were given only the water used to make the solutions for the experimental animals. After DIGE (Two-dimensional differential in gel electrophoresis) and analysis by the DeCyder software, several protein spots were found to be over-expressed (red spot) and several were under expressed (green spot) as compared to control (Figs. 4a-c). Three proteins (one was over-expressed and two were under-expressed) of each tissue (liver and urinary bladder) were identified by LC-MS/MS (liquid chromatography-tandem mass spectrometry).DIGE in combination with LC-MS/MS is a powerful tool that may help cancer investigators to understand the molecular mechanisms of cancer progression due to Inorg-As. Propose a new researchThese results suggested that selenium (Se) as well as mercury (Hg) may influence the methylation of Inorg-As and this influence could be dependent on the concentration of Se, Hg and/or the sex of the animal. Our study also suggested that the identification and functional assignment of the expressed proteins in the tissues of Inorg-As (III) exposed animals will be useful for understanding and helping to formulate a theory dealing with the molecular events of arsenic toxicity and carcinogenicity.Therefore, it would be very useful if we could do a research study with combination of Inorg-arsenic, Se, and Hg. The new research protocol could be the following:For metabolic processing, hamsters provide a good animal model. For carcinogenesis, mouse model is well accepted. The aims of this project are: 1) To map the differential distributions of arsenic (As) metabolites/species in relation to selenium (Se) and mercury (Hg) levels in male and female hamsters and 2) To chart the protein expression profile and identify the defense proteins in mice and hamsters after As injury. Experimental hamsters (male or female) will include four groups. The first group will be treated with Na arseniteNa-As(III), the second group with Na-As (III) and Na-selenite (Na-Se (IV)], the third group with Na As (III) and methyl mercuric chloride (MeHgCl), and the final group with Na-As (III), Na-Se (IV), and MeHgci at different levels. Urine and tissue will be collected at different time periods and measured for As species using high performance liquid chromatography/inductively coupled plasma-mass spectrometry (HPLC/ICP-MS). For proteomics, mice (male and female) and hamsters (male and female) will be exposed to Na-As (III)at different levels in tap water, and control mice and hamsters will be given only the tap water. Tissue will be harvested at different time periods. TWO dimensional differential in gel electrophoresis (2D-DIGE) combined with liquid chromatography-tandem mass spectrometry (LC-MS/MS) will be employed to identify the expressed protein. In summary, we intend to extend our findings to: 1) Differential distribution of As metabolites in kidney, liver, lung, and urinary bladder of male and female hamsters exposed to Na-As (III), and combined with Na-As (III) and Na-Se (IV) and/or MeHgCl at different levels and different time periods, 2) Show the correlation of As species distribution in the tissue and urine for both male and female hamsters treated with and without Na-Se (IV) and/or MeHgCl, and 3) Show protein expression profile and identify the defense proteins in the tissues (liver, lung, and urinary bladder epithelium) in mice after arsenic injury. The significance of this study: The results of which have the following significances: (A) Since Inorg-As is a human carcinogen, understanding how its metabolism is influenced by environmental factors may help understand its toxicity and carcinogenicity, (B) The interactions between arsenic (As), selenium (Se), and mercury (Hg) are of practical significance because populations in various parts of the world are simultaneously exposed to Inorg-As & Se and/or MeHg, (C) These interactions may inhibit the biotransformation of Inorg-As (III) which could increase the amount and toxicity of Inorg-As (III) and MMA (III) in the tissues, (D) Determination of arsenic species profile in the tissues after ingestion of Inorg-As (III), Se (IV), and/or MeHg+ will help understand the tissue specific influence of Se and Hg on Inorg-As (III) metabolism, (E) Correlation of arsenic species between tissue and urine might help to understand the tissue burden of arsenic species when researchers just know the distribution of arsenic species in urine, (F) The identification of the defense proteins (over-expressed and under-expressed) in the tissues of the mouse may lead to understanding the mechanisms of inorganic arsenic injury in human. The Superfund Basic Research Program NIEHS Grant Number ES 04940 from the National Institute of Environmental Health Sciences supported this work. Additional support for the mass spectrometry analyses was provided by grants from NIWHS ES 06694, NCI CA 023074 and the BIO5 Institute of the University of Arizona. Acknowledge:The Authorwantsto dedicate this paper to the memory of Dr. H. VaskenAposhian and Dr. Mary M. Aposhian who collected urine and bloodsamples from Mexican population. The work was done under Prof. H. V. Aposhian sole supervision and with his great contribution. References NRC (National Research Council). Arsenic in Drinking Water. Update to the 1999 Arsenic in Drinking Water Report. National Academy Press, Washington, DC. 2001. Gomez-Caminero, A.; Howe, P.; Hughes, M.; Kenyon, ; Lewis, D. R.; Moore, J.; Mg, J.; Aitio, A.; Becking, G. Environmental Health Criteria 224. Arsenic and Arsenic Compounds (Second Edition). 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Heavy metals contamination is a serious threat to all life forms. Long term exposure of heavy metals can lead to different life-threatening medical conditions including cancers of different body parts. Phytoremediation and bioremediation offer a potential eco-friendly solution to such problems. Different microbes can interact with heavy metals in a variety of ways such as biotransformation, oxidation/reduction, and biosorption. Phytoremediation of the heavy metals using plants mostly involves rhizofilteration, phytoextraction, phytovolatization, and Phyto stabilization. A synergistic approach using both plants and microbes has proven much more efficient as compared to the individual applications of microbes or plants. This article aims to highlight the synergistic methods used in bioremediation, emphasizing the potent collaboration between bacteria and plants for environmental cleaning, along with the discussion of the importance of site-specific variables and potential constraints. 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Hamsters were exposed to sodium arsenite (173 mg As/L) in drinking water for 6 days. Equal amounts of proteins from urinary bladder or liver extracts of control and arsenic-treated hamsters were labeled with Cy3 and Cy5 dyes, respectively. After differential in gel electrophoresis and analysis by the DeCyder software, several protein spots were found to be down-regulated and several were up regulated. Our experiments indicated that in the bladder tissues of hamsters exposed to arsenite, transgelin was down-regulated and GST-pi was up-regulated. The loss of transgelin expression has been reported to be an important early event in tumor progression and a diagnostic marker for cancer development [29-32]. Down-regulation of transgelin expression may be associated with the carcinogenicity of inorganic arsenic in the urinary bladder. In the liver of arsenite-treated hamsters, ornithine aminotransferase was up-regulated, and senescence marker protein 30 and fatty acid binding protein were down-regulated. The volume ratio changes of these proteins in the bladder and liver of hamsters exposed to arsenite were significantly different than that of control hamsters. Introduction Chronic exposure to inorganic arsenic can cause cancer of the skin, lungs, urinary bladder, kidneys, and liver [1-6]. The molecular mechanisms of the carcinogenicity and toxicity of inorganic arsenic are not well understood [7-9). Humans chronically exposed to inorganic arsenic excrete MMA(V), DMA(V) and the more toxic +3 oxidation state arsenic biotransformants MMA(III) and DMA (III) in their urine [10, 11], which are carcinogen [12]· After injection of mice with sodium arsenate, the highest concentrations of the very toxic MMA(III) and DMA(III) were in the kidneys and urinary bladder tissue, respectively, as shown by experiments of Chowdhury et al [13]. Many mechanisms of arsenic toxicity and carcinogenicity have been suggested [1, 7, 14] including chromosome abnormalities [15], oxidative stress [16, 17], altered growth factors [18], cell proliferation [19], altered DNA repair [20], altered DNA methylation patterns [21], inhibition of several key enzymes [22], gene amplification [23] etc. Some of these mechanisms result in alterations in protein expression. Methods for analyzing multiple proteins have advanced greatly in the last several years. In particularly, mass spectrometry (MS) and tandem MS (MS/MS) are used to analyze peptides following protein isolation using two-dimensional (2-D) gel electrophoresis and proteolytic digestion [24]. In the present study, Differential In Gel Electrophoresis (DIGE) coupled with Mass Spectrometry (MS) has been used to study some of the proteomic changes in the urinary bladder and liver of hamsters exposed to sodium arsenite in their drinking water. Our results indicated that transgelin was down-regulated and GST-pi was up-regulated in the bladder tissues. In the liver tissues ornithine aminotransferase was up-regulated, and senescence marker protein 30, and fatty acid binding protein were down-regulated. Materials and Methods Chemicals Tris, Urea, IPG strips, IPG buffer, CHAPS, Dry Strip Cover Fluid, Bind Silane, lodoacetamide, Cy3 and Cy5 were from GE Healthcare (formally known as Amersham Biosciences, Uppsala, Sweden). Thiourea, glycerol, SDS, DTT, and APS were from Sigma-Aldrich (St. Louis, MO, USA). Glycine was from USB (Cleveland, OH, USA). Acrylamide Bis 40% was from Bio-Rad (Hercules, CA, USA). All other chemicals and biochemicals used were of analytical grade. All solutions were made with Milli-Q water. Animals Male hamsters (Golden Syrian), 4 weeks of age, were purchased from Harlan Sprague Dawley, USA. Upon arrival, hamsters were acclimated in the University of Arizona animal care facility for at least 1 week and maintained in an environmentally controlled animal facility operating on a 12-h dark/12-h light cycle and at 22-24°C. They were provided with Teklad (Indianapolis, IN) 4% Mouse/Rat Diet # 7001 and water, ad libitum, throughout the acclimation and experimentation periods. Sample preparation and labelling Hamsters were exposed to sodium arsenite (173 mg) in drinking water for 6 days and the control hamsters were given tap water. On the 6th day hamsters were decapitated rapidly by guillotine. Urinary bladder tissues and liver were removed, blotted on tissue papers (Kimtech Science, Precision Wipes), and weighed. Hamster urinary bladder or liver tissues were homogenized in lysis buffer (30mMTris, 2M thiourea, 7M urea, and 4% w/w CHAPS adjusted to pH 8.5 with dilute HCI), at 4°C using a glass homogenizer and a Teflon coated steel pestle; transferred to a 5 ml acid-washed polypropylene tube, placed on ice and sonicated 3 times for 15 seconds. The sonicate was centrifuged at 12,000 rpm for 10 minutes at 4°C. Small aliquots of the supernatants were stored at -80°C until use (generally within one week). Protein concentration was determined by the method of Bradford [25] using bovine serum albumin as a standard. Fifty micrograms of lysate protein was labeled with 400 pmol of Cy3 Dye (for control homogenate sample) and Cy5 Dye (for arsenic-treated urinary bladder or liver homogenate sample). The samples containing proteins and dyes were incubated for 30 min on ice in the dark. To stop the labeling reaction, 1uL of 10 mM lysine was added followed by incubation for 10 min on ice in the dark. To each of the appropriate dye-labeled protein samples, an additional 200 ug of urinary bladderor liver unlabeled protein from control hamster sample or arsenic-treated hamster sample was added to the appropriate sample. Differentially labeled samples were combined into a single Microfuge tube (total protein 500 ug); protein was mixed with an equal volume of 2x sample buffer [2M thiourea, 7M urea, pH 3-10 pharmalyte for isoelectric focusing 2% (v/v), DTT 2% (w/v), CHAPS 4% (w/v)]; and was incubated on ice in the dark for 10 min. The combined samples containing 500 ug of total protein were mixed with rehydration buffer [CHAPS 4% (w/v), 8M urea, 13mM DTT, IPG buffer (3-10) 1% (v/v) and trace amount of bromophenol blue]. The 450 ul sample containing rehydration buffer was slowly pipetted into the slot of the ImmobilinedryStripReswelling Tray and any large bubbles were removed. The IPG strip (linear pH 3-10, 24 cm) was placed (gel side down) into the slot, covered with drystrip cover fluid (Fig. 1), and the lid of the Reswelling Tray was closed. The ImmobillineDryStrip was allowed to rehydrate at room temperature for 24 hours. First dimension Isoelectric focusing (IEF) The labeled sample was loaded using the cup loading method on universal strip holder. IEF was then carried out on EttanIPGphor II using multistep protocol (6 hr @ 500 V, 6 hr @ 1000 V, 8 hr @ 8000 V). The focused IPG strip was equilibrated in two steps (reduction and alkylation) by equilibrating the strip for 10 min first in 10 ml of 50mM Tris (pH 8.8), 6M urea, 30% (v/v) glycerol, 2% (w/v) SDS, and 0.5% (w/v) DTT, followed by another 10 min in 10 ml of 50mM Tris (pH 8.8), 6M urea, 30% (v/v) glycerol, 2% (w/v) SDS, and 4.5% (w/v) iodoacetamide to prepare it for the second dimension electrophoresis. Second dimension SDS-PAGE The equilibrated IPG strip was used for protein separation by 2D-gel electrophoresis (DIGE). The strip was sealed at the top of the acrylamide gel for the second dimension (vertical) (12.5% polyacrylamide gel, 20x25 cm x 1.5 mm) with 0.5% (w/v) agarose in SDS running buffer [25 mMTris, 192 mM Glycine, and 0.1% (w/v) SDS]. Electrophoresis was performed in an Ettan DALT six electrophoresis unit (Amersham Biosciences) at 1.5 watts per gel, until the tracking dye reached the anodic end of the gel. Image analysis and post-staining The gel then was imaged directly between glass plates on the Typhoon 9410 variable mode imager (Sunnyvale, CA, USA) using optimal excitation/emission wavelength for each DIGE fluor: Cy3 (532/580 nm) and Cy5 (633/670 nm). The DIGE images were previewed and checked with Image Quant software (GE Healthcare) where all the two separate gel images could be viewed as a single gel image. DeCyde v.5.02 was used to analyze the DIGE images as described in the Ettan DIGE User Manual (GE Healthcare). The appropriate up-/down regulated spots were filtered based on an average volume ratio of ± over 1.2 fold. After image acquisition, the gel was fixed overnight in a solution containing 40% ethanol and 10% acetic acid. The fixed gel was stained with SyproRuby (BioRad) according to the manufacturer protocol (Bio-Rad Labs., 2000 Alfred Nobel Drive, Hercules, CA 94547). Identification of proteins by MS Protein spot picking and digestion Sypro Ruby stained gels were imaged using an Investigator ProPic and HT Analyzer software, both from Genomic Solutions (Ann Arbor, MI). Protein spots of interest that matched those imaged using the DIGE Cy3/Cy5 labels were picked robotically, digested using trypsin as described previously [24] and saved for mass spectrometry identification. Liquid chromatography (LC)- MS/MS analysis LC-MS/MS analyses were carried out using a 3D quadrupole ion trap massspectrometer (ThermoFinnigan LCQ DECA XP PLUS; ThermoFinnigan, San Jose, CA) equipped with a Michrom Paradigm MS4 HPLC (MichromBiosources, Auburn, CA) and a nanospray source, or with a linear quadrupole ion trap mass spectrometer (ThermoFinnigan LTQ), also equipped with a Michrom MS4 HPLC and a nanospray source. Peptides were eluted from a 15 cm pulled tip capillary column (100 um I.D. x 360 um O.D.; 3-5 um tip opening) packed with 7 cm Vydac C18 (Vydac, Hesperia, CA) material (5 µm, 300 Å pore size), using a gradient of 0-65% solvent B (98% methanol/2% water/0.5% formic acid/0.01% triflouroacetic acid) over a 60 min period at a flow rate of 350 nL/min. The ESI positive mode spray voltage was set at 1.6 kV, and the capillary temperature was set at 200°C. Dependent data scanning was performed by the Xcalibur v 1.3 software on the LCQ DECA XP+ or v 1.4 on the LTQ [27], with a default charge of 2, an isolation width of 1.5 amu, an activation amplitude of 35%, activation time of 50 msec, and a minimal signal of 10,000 ion counts (100 ion counts on the LTQ). Global dependent data settings were as follows: reject mass width of 1.5 amu, dynamic exclusion enabled, exclusion mass width of 1.5 amu, repeat count of 1, repeat duration of a min, and exclusion duration of 5 min. Scan event series were included one full scan with mass range of 350-2000 Da, followed by 3 dependent MS/MS scans of the most intense ion. Database searching Tandem MS spectra of peptides were analyzed with Turbo SEQUEST, version 3.1 (ThermoFinnigan), a program that allows the correlation of experimental tandem MS data with theoretical spectra generated from known protein sequences. All spectra were searched against the latest version of the non redundant protein database from the National Center for Biotechnology Information (NCBI 2006; at that time, the database contained 3,783,042 entries). Statistical analysis The means and standard error were calculated. The Student's t-test was used to analyze the significance of the difference between the control and arsenite exposed hamsters. P values less than 0.05 were considered significant. The reproducibility was confirmed in separate experiments. Results Analysis of proteins expression After DIGE (Fig. 1), the gel was scanned by a Typhoon Scanner and the relative amount of protein from sample 1 (treated hamster) as compared to sample 2 (control hamster) was determined (Figs. 2, 3). A green spot indicates that the amount of protein from sodium arsenite-treated hamster sample was less than that of the control sample. A red spot indicates that the amount of protein from the sodium arsenite-treated hamster sample was greater than that of the control sample. A yellow spot indicates sodium arsenite-treated hamster and control hamster each had the same amount of that protein. Several protein spots were up-regulated (red) or down-regulated (green) in the urinary bladder samples of hamsters exposed to sodium arsenite (173 mg As/L) for 6 days as compared with the urinary bladder of controls (Fig. 2). In the case of liver, several protein spots were also over-expressed (red) or under-expressed (green) for hamsters exposed to sodium arsenite (173 mg As/L) in drinking water for 6 days (Fig. 3). The urinary bladder samples were collected from the first and second experiments in which hamsters were exposed to sodium arsenite (173 mg As/L) in drinking water for 6 days and the controls were given tap water. The urinary bladder samples from the 1st and 2nd experiments were run 5 times in DIGE gels on different days. The protein expression is shown in Figure 2 and Table 1. The liver samples from the 1st and 2nd experiments were also run 3 times in DIGE gels on different days. The proteins expression were shown in Figure 3 and Table 2. The volume ratio changed of the protein spots in the urinary bladder and liver of hamsters exposed to arsenite were significantly differences than that of the control hamsters (Table 1 and 2). Protein spots identified by LC-MS/MS Bladder The spots of interest were removed from the gel, digested, and their identities were determined by LC-MS/MS (Fig. 2 and Table 1). The spots 1, 2, & 3 from the gel were analyzed and were repeated for the confirmation of the results (experiments; 173 mg As/L). The proteins for the spots 1, 2, and 3 were identified as transgelin, transgelin, and glutathione S-transferase Pi, respectively (Fig. 2). Liver We also identified some of the proteins in the liver samples of hamsters exposed to sodium arsenite (173 mg As/L) in drinking water for 6 days (Fig. 3). The spots 4, 5, & 6 from the gels were analyzed and were repeated for the confirmation of the results. The proteins for the spots 4, 5, and 6 were identified as ornithine aminotransferase, senescence marker protein 30, and fatty acid binding protein, respectively (Fig. 3) Discussion The identification and functional assignment of proteins is helpful for understanding the molecular events involved in disease. Weexposed hamsters to sodium arsenite in drinking water. Controls were given tap water. DIGE coupled with LC-MS/MS was then used to study the proteomic change in arsenite-exposed hamsters. After electrophoresis DeCyder software indicated that several protein spots were down-regulated (green) and several were up-regulated (red). Our overall results as to changes and functions of the proteins we have studied are summarized in Table 3. Bladder In the case of the urinary bladder tissue of hamsters exposed to sodium arsenite (173 mg As/L) in drinking water for 6 days, transgelin was down-regulated and GST-pi was up-regulated. This is the first evidence that transgelin is down-regulated in the bladders of animals exposed to sodium arsenite. Transgelin, which is identical to SM22 or WS3-10, is an actin cross linking/gelling protein found in fibroblasts and smooth muscle [28, 29]. It has been suggested that the loss of transgelin expression may be an important early event in tumor progression and a diagnostic marker for cancer development [30-33]. It may function as a tumor suppressor via inhibition of ARA54 (co-regulator of androgen receptor)-enhanced AR (androgen receptor) function. Loss of transgelin and its suppressor function in prostate cancer might contribute to the progression of prostate cancer [30]. Down-regulation of transgelin occurs in the urinary bladders of rats having bladder outlet obstruction [32]. Ras-dependent and Ras-independent mechanisms can cause the down regulation of transgelin in human breast and colon carcinoma cell lines and patient-derived tumorsamples [33]. Transgelin plays a role in contractility, possibly by affecting the actin content of filaments [34]. In our experiments loss of transgelin expression may be associated or preliminary to bladder cancer due to arsenic exposure. Arsenite is a carcinogen [1]. In our experiments, LC-MS/MS analysis showed that two spots (1 and 2) represent transgelin (Fig. 2 and Table 1). In human colonic neoplasms there is a loss of transgelin expression and the appearance of transgelin isoforms (31). GST-pi protein was up-regulated in the bladders of the hamsters exposed to sodium arsenite. GSTs are a large family of multifunctional enzymes involved in the phase II detoxification of foreign compounds [35]. The most abundant GSTS are the classes alpha, mu, and pi classes [36]. They participate in protection against oxidative stress [37]. GST-omega has arsenic reductase activity [38]. Over-expression of GST-pi has been found in colon cancer tissues [39]. Strong expression of GST-pi also has been found in gastric cancer [40], malignant melanoma [41], lung cancer [42], breast cancer [43] and a range of other human tumors [44]. GST-pi has been up-regulated in transitional cell carcinoma of human urinary bladder [45]. Up-regulation of glutathione – related genes and enzyme activities has been found in cultured human cells by sub lethal concentration of inorganic arsenic [46]. There is evidence that arsenic induces DNA damage via the production of ROS (reactive oxygen species) [47]. GST-pi may be over-expressed in the urinary bladder to protect cells against arsenic-induced oxidative stress. Liver In the livers of hamsters exposed to sodium arsenite, ornithine amino transferase was over-expressed, senescence marker protein 30 was under-expressed, and fatty acid binding protein was under-expressed. Ornithine amino transferase has been found in the mitochondria of many different mammalian tissues, especially liver, kidney, and small intestine [48]. Ornithine amino transferase knockdown inhuman cervical carcinoma and osteosarcoma cells by RNA interference blocks cell division and causes cell death [49]. It has been suggested that ornithine amino transferase has a role in regulating mitotic cell division and it is required for proper spindle assembly in human cancer cells [49]. Senescence marker protein-30 (SMP30) is a unique enzyme that hydrolyzes diisopropylphosphorofluoridate. SMP30, which is expressed mostly in the liver, protects cells against various injuries by stimulating membrane calcium-pump activity [50]. SMP30 acts to protect cells from apoptosis [51]. In addition it protects the liver from toxic agents [52]. The livers of SMP30 knockout mice accumulate phosphatidylethanolamine, cardiolipin, phosphatidyl-choline, phosphatidylserine, and sphingomyelin [53]. Liver fatty acid binding protein (L-FABP) also was down- regulated. Decreased liver fatty acid-binding capacity and altered liver lipid distribution hasbeen reported in mice lacking the L-FABP gene [54]. High levels of saturated, branched-chain fatty acids are deleterious to cells and animals, resulting in lipid accumulation and cytotoxicity. The expression of fatty acid binding proteins (including L-FABP) protected cells against branched-chain saturated fatty acid toxicity [55]. Limitations: we preferred to study the pronounced spots seen in DIGE gels. Other spots were visible but not as pronounced. Because of limited funds, we did not identify these others protein spots. In conclusion, urinary bladders of hamsters exposed to sodium arsenite had a decrease in the expression of transgelin and an increase in the expression of GST-pi protein. Under-expression of transgelin has been found in various cancer systems and may be associated with arsenic carcinogenicity [30-33). Inorganic arsenic exposure has resulted in bladder cancer as has been reported in the past [1]. Over-expression of GST-pi may protect cells against oxidative stress caused by arsenite. In the liver OAT was up regulated and SMP-30 and FABP were down regulated. These proteomic results may be of help to investigators studying arsenic carcinogenicity. The Superfund Basic Research Program NIEHS Grant Number ES 04940 from the National Institute of Environmental Health Sciences supported this work. Additional support for the mass spectrometry analyses was provided by grants from NIWHS ES06694, NCI CA023074 and the BIOS Institute of the University of Arizona. Acknowledgement The Author wants to dedicate this paper to the memory of his former supervisor Dr. H. VaskenAposhian who passed away in September 6, 2019. He was an emeritus professor of the Department of Molecular and Cellular Biology at the University of Arizona. 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This study aimed to analyze the correlation between Human Capital Sustainability Leadership style and manager resilience through a pragmatic worldview. Using explanatory sequential mixed methods research design (QUAN→qual), respondents covered were managers from the Airline Operations Group of an AIRLINE Company with at least one year of managerial experience within the organization. In the quantitative phase, Human Capital Sustainability Leadership Scale by Di Fabio and Peiro (2018) and Domain-Specific Resilient Systems Scales (DRSSWork) by Maltby, Day, Hall, and Chivers (2019) were used for the online survey. Forty-five (45) eligible respondents have participated. Mean, standard deviation, and Spearman rank correlation coefficient were employed. To further explain the quantitative results, one-on-one qualitative interviews were done with eight (8) key informants, face-toface and online. Themes were identified. Results showed that Human Capital Sustainability Leadership style was exhibited by the Airline Operations Group managers to a very high degree while resilience was exhibited to a high degree. There was a linear, positive, and highly significant correlation between Human Capital Sustainability Leadership style and resilience. Each aspect of the Human Capital Sustainability Leadership style was positively, highly, and significantly correlated with manager resilience. Through triangulation, a model of leadership styles and manager resiliency was built. To implement the model, implications for a management development program were identified.ReferencesAcosta, H., Cruz-Ortiz, V., Salanova, M., & Llorens S. (2015). Healthy organization: Analysing its meaning based on the HERO model. Revista de Psicologia Social, 30 (2), 323-350. http://dx.doi.org/10.1080/21711976.2015.1016751.Ashegi, M. & Hashemi, E. (2019). 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Herbal extract, rich with natural compounds, has been used for medicinal purpose such as treating neurological disorders such as cognitive defection for a long period of time, often without significant adverse effects. We compared AChE and BuChE – inhibition effect of total extracts and fractions of Huperzia serrata (Thunb.) Trevis. with alcaloid-rich extract. Our samples were subjected under supersonic extraction with ethanol 50o as solvent and fractionally extracted with n-hexane, EtOAc and n-butanol, respectively; alcaloid-rich extract was collected simutaneously. Ellman’s method was used to assay AChE and BuChE inhibition activity. Results: Alcaloid-rich extraction proved to be the superior AChE inhibiting agent, its activity nearly 6 fold of the most active Huperzia serrata extraction with IC50 value of 7.93 (5.43-10.98) µg/ml. While the fractions as well as the total extract did not provide any BuChE inhibition activity, alcaloid-rich extract showed weak ability (IC50 at 76.67 (64.78 – 91.84) µg/ml). Overall, the superior enzyme inhibition effect of alcaloid-rich extract might open a new approach in preventing and treating neurological disorders such as alzheimer’s. Keywords Huperzia serrata (Thunb.) Trevis, alcaloid, Acetylcholinesrerase inhibitors (AChE); butyrylcholinesterase (BuChE), Alzheimer. References [1] Dos Santos Picanco, Leide C et al., Alzheimer's disease: A review from the pathophysiology to diagnosis, new perspectives for pharmacological treatment, Current medicinal chemistry 25(26) (2018) 3141 - 3159. https://doi.org/10.2174/0929867323666161213101126.[2] B.M. McGleenon, K.B. Dynan, A.P. 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Canadian Journal of Chemistry 64(4) (1986) 837-839. https://doi.org/10.1139/v86-137.[7] Takuya Ohba, Yuta Yoshino et al., Japanese Huperzia serrata extract and the constituent, huperzine A, ameliorate the scopolamine-induced cognitive impairment in mice, Bioscience biotechnology and biochemistry 79(11) (2015) 1838-1844. https://doi.org/10.1080/09168451.2015.1052773.[8] Ju-Yeon Park, Hyuck Kim et al., Ethanol Extract of Lycopodium serratum Thunb. Attenuates Lipopolysaccharide-Induced C6 Glioma Cells Migration via Matrix Metalloproteinase-9 Expression, Chinese Journal of Integrative Medicine 24(11) (2018) 860-866. https://doi.org/10.1007/s11655-017-2923-9.[9] M. Maridass, G. Raju, Investigation of phytochemical and antimicrobial activity of Huperzia species, Pharmacologyonline 3 (2009) 688-692.[10] George.L.Ellman, K.Diane Courtney, et al., A new and rapid colorimetric determination of acetylcholinesterase activity, Biochemical Pharmacology 7(2) (1961) 88-95. https://doi.org/10.1016/0006-2952(61)90145-9.[11] Paul T Francis, et al., The cholinergic hypothesis of Alzheimer’s disease: a review of progress. Journal of Neurology, Neurosurgery & Psychiatry, 66(2) (1999) 137-147. http://dx.doi.org/10.1136/jnnp.66.2.137.[12] Prerna Upadhyaya, Vikas Seth, Mushtaq Ahmad, Therapy of Alzheimer’s disease: An update, African Journal of Pharmacy and Pharmacology 4(6) (2010) 408-421.[13] Hachiro Sugimoto, Hiroo Ogura, et al., Research and development of donepezil hydrochloride, a new type of acetylcholinesterase inhibitor, The Japanese journal of pharmacology 89(1) (2002) 7-20.[14] N.T.K. Thu, et al., Acetylcholinesterase and butyrylcholinesterase inhibition effect of fractions extract of Huperzia serrata (Thunb.) Trevis. The journal of Pharmeceutical 56(11) 49-53 (in Vietnamese).[15] Xiaoqiang Ma, Changheng Tan, et al, Is there a better source of huperzine A than Huperzia serrata? Huperzine A content of Huperziaceae species in China. J Agric Food Chem, 53(5) (2005)1393-8. https://doi.org/10.1021/jf048193n.[16] Ya-Bing Yang, Xue-Qiong Yang, et al., A New Flavone Glycoside from Huperzia serrata. Chinese Journal of Natural Medicines 6(6) (2008) 408-410.[17] G.T. Ha, R.K. Wong, Y. Zhang, Huperzine a as potential treatment of Alzheimer's disease: an assessment on chemistry, pharmacology, and clinical studies, Chemistry & biodiversity 8(7) (2011) 1189-1204. https://doi.org/10.1002/cbdv.201000269.[18] H.Y. Zhang, X.C. Tang, Neuroprotective effects of huperzine A: new therapeutic targets for neurodegenerative disease, Trends in pharmacological sciences 27(12) (2006) 619-625. https://doi.org/10.1016/j.tips.2006.10.004.[19] Y. Wang, X.C. Tang, H.Y. Zhang, Huperzine A alleviates synaptic deficits and modulates amyloidogenic and nonamyloidogenic pathways in APPswe/PS1dE9 transgenic mice, Journal of neuroscience research 90(2) (2012) 508-517. https://doi.org/10.1002/jnr.22775.[20] C.Y. Wang, et al., Huperzine A activates Wnt/β-catenin signaling and enhances the nonamyloidogenic pathway in an Alzheimer transgenic mouse model, Neuropsychopharmacology 36(5) (2011) 1073-1089. https://doi.org/10.1038/npp.2010.245.[21] R.K. Gordon, et al., The NMDA receptor ion channel: a site for binding of Huperzine A, Journal of applied toxicology 21(S1) (2001) S47-S51. https://doi.org/10.1002/jat.805.[22] M. 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This study uses an in silico screening docking model to evaluate the ACE2 inhibitory activity of natural compounds and drugs. The study collected 49 compounds and evaluated the ACE2 inhibitory effect in silico. The study results show that 11 out of the 49 compounds had stronger inhibitory activity on ACE2 than MLN-4760. Lipinski’s rule of five criteria and predictive pharmacokinetic-toxicity analysis show that eight compounds including quercetin, galangin, quisinostat, fluprofylline, spirofylline, RS 504393, TNP and GNF-5 had drug-likeness. These compounds could be potential drug for the Covid-19 treatment. Keywords SARS-CoV-2S, Covid-19, ACE2, molecular docking, in silico. References [[1] C. Wang, P.W. Horby, F.G. Hayden, G.F. Gao. A novel coronavirus outbreak of global health concern. The Lancet 395(10223) (2020) 470.[2] WHO. WHO Coronavirus Disease (COVID-19) Dashboard. WHO, 2020.[3] N. Chen, M. Zhou, X. Dong, J. Qu, F. Gong, Y. Han, et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. The Lancet 395(10223) (2020) 507.[4] J. Yang, Y. Zheng, X. Gou, K. Pu, Z. Chen, Q. Guo, et al. Prevalence of comorbidities and its effects in patients infected with SARS-CoV-2: a systematic review and meta-analysis. International Journal of Infectious Diseases 94 (2020) 91.[5] R. Lu, X. Zhao, J. Li, P. Niu, B. Yang, H. Wu, et al. Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. The Lancet 395(10224) (2020) 565.[6] R. Hilgenfeld. From SARS to MERS: crystallographic studies on coronaviral proteases enable antiviral drug design. The FEBS journal 281(18) (2014) 4085.[7] D. Wrapp, N. Wang, K.S. Corbett, J.A. Goldsmith, C.L. Hsieh, O. Abiona, et al. Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation. Science (New York, NY) 367(6483) (2020) 1260.[8] P.A. Rota, M.S. 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Penelitian ini bertujuan untuk menguji dan menganalisa pengaruh konflik peran dan ambiguitas terhadap kinerja melalui kepuasan kerja pada tenaga fungsional RSUD Sekadau. Metode penelitian yang digunakan merupakan jenis penelitian non-eksperimental dengan pendekatan kuantitatif, deskriptif korelasi dan desain cross-sectional. Populasi dalam penelitian ini adalah seluruh tenaga fungsional RSUD Sekadau yang berjumlah 181 orang dengan sampel yang diambil adalah 123 orang tenaga fungsional RSUD Sekadau. Alat analisis yang digunakan adalah analisis jalur (path analysis) dengan metode SEM (structural equation modelling) menggunakan WarpPLS versi 6.0. Hasil penelitian menunjukkan terdapat pengaruh positif signifikan konflik peran terhadap kinerja, terdapat pengaruh negatif signifikan ambiguitas terhadap kinerja, terdapat pengaruh negatif signifikan antara konflik peran dan ambiguitas terhadap kepuasan kerja, terdapat pengaruh negatif signifikan kepuasan kerja terhadap kinerja, terdapat pengaruh positif signifikan antara konflik peran dan ambiguitas terhadap kinerja melalui kepuasan kerja. Nilai profesionalisme menjadi penting untuk variabel konflik peran, tanggung jawab menjadi faktor penting untuk variabel ambiguitas, hubungan yang baik dengan profesi lain di Rumah Sakit menjadi penting untuk variabel kepuasan kerja dan karyawan memahami harapan pekerjaan dan tetap melaksanakannya sesuai dengan tanggung jawab merupakan nilai penting untuk variabel kinerja. Kata kunci : Konflik Peran, Ambiguitas, Kepuasan Kerja, KinerjaDAFTAR PUSTAKAAhmed, S., Manaf, N.H.A., & Islam, R. (2017). 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Diabetes Mellitus has been becoming a disease of the century, and disease incidence is still rising worldwide. It causes many serious complications, especially in the eye, heart, kidneys, brain, and vascular system, such as diabetic nephropathy, diabetic retinopathy, liver fa­ilure, etc. Moreover, the process of controlling this disease is complicated. Meanwhile, the antidiabetic drugs on the market are facing some problems with a wide range of adverse reactions. Therefore, finding new drugs to treat diabetes has always been a topic that many researchers are interested in, especially drugs derived from nature like microorganisms and medicinal plants. This review is to provide knowledge concerning the effects of α-glucosidase inhibitors, which are oral antidiabetic drugs commonly used for diabetes mellitus type 2. Besides, we show readers the variety of active ingredients originating from nature, particularly the secondary metabolites of Aspergillus spp., which have many applications in the chemical and medicinal industry. Keywords: Diabetes, α-glucosidase inhibitors, Aspergillus. References [1] W. H. Organization, Classification of Diabetes Mellitus, https://www.who.int/westernpacific/health-topics/diabetes (accessed on: May 11th, 2021).[2] J. Thrasher, Pharmacologic Management of Type 2 Diabetes Mellitus: Available Therapies, Am J Cardiol, Vol. 120, No. 1, 2017, pp. S4-S16, https://doi.org/10.1016/j.amjcard.2017.05.009.[3] W. Hakamata, M. Kurihara, H. Okuda, T. Nishio, T. Oku, Design and Screening Strategies for Alpha-glucosidase Inhibitors Based on Enzymological Information, Curr Top Med Chem, Vol. 9, No. 1, 2009, pp. 3-12, https://doi.org/10.2174/156802609787354306.[4] US, Patent Version Number: US4062950A, Amino Sugar Derivatives, https://patents.google.com/patent/US4062950A/en(accessed on: May 11th, 2021).[5] A. S. Dabhi, N. R. Bhatt, M. J. Shah, Voglibose: an Alpha- glucosidase Inhibitor, J Clin Diagn Res, Vol. 7, No. 12, 2013, pp. 3023-3027, https://doi.org/10.7860/JCDR/2013/6373.3838.[6] P. Durruty, M. Sanzana, L. Sanhueza, Pathogenesis of Type 2 Diabetes Mellitus, Type 2 Diabetes - from Pathophysiology to Modern Management, Intechopen, United Kingdom, 2019, pp. 1-18.[7] L. N. Khue, T. H. Dang, T. H. Quang, N. T. Khue et al., Guidelines for Diagnosis and Treatment of Diabetes Type 2, Ministry of Health, Vietnam, 2021 (in Vietnamese).[8] M. Okuyama, W. Saburi, H. Mori, A. 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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel coronavirus , is causing a serious worldwide COVID-19 pandemic. The emergence of strains with rapid spread and unpredictable changes is the cause of the increase in morbidity and mortality rates. A number of drugs as well as vaccines are currently being used to relieve symptoms, prevent and treat the disease caused by this virus. However, the number of approved drugs is still very limited due to their effectiveness and side effects. In such a situation, medicinal plants and bioactive compounds are considered a highly valuable source in the development of new antiviral drugs against SARS-CoV-2. This review summarizes medicinal plants and bioactive compounds that have been shown to act on molecular targets involved in the infection and replication of SARS-CoV-2. Keywords: Medicinal plants, bioactive compounds, antivirus, SARS-CoV-2, COVID-19 References [1] R. Lu, X. Zhao, J. Li, P. Niu, B. Yang, H. 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Concentrations of 16 polycyclic aromatic hydrocarbons (PAHs) were determined in settled house dust and road dust samples collected from a core urban area of Hanoi. Levels of PAHs ranged from 830 to 3500 (median 2000) ng/g in house dust, and from 1400 to 4700 (median 1700) ng/g in road dust. Concentrations of PAHs in dust samples of this study were within the moderate range as compared with those from other countries in the world. Toxic equivalents to benzo[a]pyrene (BaP-EQs) in our samples ranged from 81 to 850 (median 330) ng BaP-EQ/g with principal contributors as BaP and dibenz[a,h]anthracene, which accounted for 69% to 93% of BaP-EQs. In almost all the samples, proportions of high-molecular-weight PAHs (HMW-PAHs with 4–6 rings) were higher than those of low-molecular-weight PAHs (LMW-PAHs with 2–3 rings), suggesting emission sources from combustion processes rather than direct contamination by petrogenic sources. 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About half way through Yann Arthus-Bertrand’s film Home (2009) the narrator describes the fall of the Rapa Nui, the indigenous people of the Easter Islands. The narrator posits that the Rapa Nui culture collapsed due to extensive environmental degradation brought about by large-scale deforestation. The Rapa Nui cut down their massive native forests to clear spaces for agriculture, to heat their dwellings, to build canoes and, most importantly, to move their enormous rock sculptures—the Moai. The disappearance of their forests led to island-wide soil erosion and the gradual disappearance of arable land. Caught in the vice of overpopulation but with rapidly dwindling basic resources and no trees to build canoes, they were trapped on the island and watched helplessly as their society fell into disarray. The sequence ends with the narrator’s biting remark: “The real mystery of the Easter Islands is not how its strange statues got there, we know now; it's why the Rapa Nui didn't react in time.” In their unrelenting desire for development, the Rapa Nui appear to have overlooked the role the environment plays in maintaining a society. The island’s Moai accompanying the sequence appear as memento mori, a lesson in the mortality of human cultures brought about by their own misguided and short-sighted practices. Arthus-Bertrand’s Home, a film composed almost entirely of aerial photographs, bears witness to present-day environmental degradation and climate change, constructing society as a fragile structure built upon and sustained by the environment. Home is a call to recognise how contemporary practices of post-industrial societies have come to shape the environment and how they may impact the habitability of Earth in the near future. Through reflexivity and a ritualised structure the text invites spectators to look at themselves in a new light and remake their self-image in the wake of global environmental risk by embracing new, alternative core practices based on balance and interconnectedness. Arthus-Bertrand frames climate change not as a burden, but as a moment of profound realisation of the potential for change and humans ability to create a desirable future through hope and our innate capacity for renewal. This article examines how Arthus-Bertrand’s ritualised construction of climate change aims to remake viewers’ perception of present-day environmental degradation and investigates Home’s place in contemporary climate change communication discourse. Climate change, in its capacity to affect us globally, is considered a world risk. The most recent peer-reviewed Synthesis Report of the Intergovernmental Panel on Climate Change suggests that the concentration of atmospheric greenhouse gases has increased markedly since human industrialisation in the 18th century. Moreover, human activities, such as fossil fuel burning and agricultural practices, are “very likely” responsible for the resulting increase in temperature rise (IPPC 37). The increased global temperatures and the subsequent changing weather patterns have a direct and profound impact on the physical and biological systems of our planet, including shrinking glaciers, melting permafrost, coastal erosion, and changes in species distribution and reproduction patterns (Rosenzweig et al. 353). Studies of global security assert that these physiological changes are expected to increase the likelihood of humanitarian disasters, food and water supply shortages, and competition for resources thus resulting in a destabilisation of global safety (Boston et al. 1–2). Human behaviour and dominant practices of modernity are now on a path to materially impact the future habitability of our home, Earth. In contemporary post-industrial societies, however, climate change remains an elusive, intangible threat. Here, the Arctic-bound species forced to adapt to milder climates or the inhabitants of low-lying Pacific islands seeking refuge in mainland cities are removed from the everyday experience of the controlled and regulated environments of homes, offices, and shopping malls. Diverse research into the mediated and mediatised nature of the environment suggests that rather than from first-hand experiences and observations, the majority of our knowledge concerning the environment now comes from its representation in the mass media (Hamilton 4; Stamm et al. 220; Cox 2). Consequently the threat of climate change is communicated and constructed through the news media, entertainment and lifestyle programming, and various documentaries and fiction films. It is therefore the construction (the representation of the risk in various discourses) that shapes people’s perception and experience of the phenomenon, and ultimately influences behaviour and instigates social response (Beck 213). By drawing on and negotiating society’s dominant discourses, environmental mediation defines spectators’ perceptions of the human-nature relationship and subsequently their roles and responsibilities in the face of environmental risks. Maxwell Boykoff asserts that contemporary modern society’s mediatised representations of environmental degradation and climate change depict the phenomena as external to society’s primary social and economic concerns (449). Julia Corbett argues that this is partly because environmental protection and sustainable behaviour are often at odds with the dominant social paradigms of consumerism, economic growth, and materialism (175). Similarly, Rowan Howard-Williams suggests that most media texts, especially news, do not emphasise the link between social practices, such as consumerist behaviour, and their environmental consequences because they contradict dominant social paradigms (41). The demands contemporary post-industrial societies make on the environment to sustain economic growth, consumer culture, and citizens’ comfortable lives in air-conditioned homes and offices are often left unarticulated. While the media coverage of environmental risks may indeed have contributed to “critical misperceptions, misleading debates, and divergent understandings” (Boykoff 450) climate change possesses innate characteristics that amplify its perception in present-day post-industrial societies as a distant and impersonal threat. Climate change is characterised by temporal and spatial de-localisation. The gradual increase in global temperature and its physical and biological consequences are much less prominent than seasonal changes and hence difficult to observe on human time-scales. Moreover, while research points to the increased probability of extreme climatic events such as droughts, wild fires, and changes in weather patterns (IPCC 48), they take place over a wide range of geographical locations and no single event can be ultimately said to be the result of climate change (Maibach and Roser-Renouf 145). In addition to these observational obstacles, political partisanship, vested interests in the current status quo, and general resistance to profound change all play a part in keeping us one step removed from the phenomenon of climate change. The distant and impersonal nature of climate change coupled with the “uncertainty over consequences, diverse and multiple engaged interests, conflicting knowledge claims, and high stakes” (Lorenzoni et al. 65) often result in repression, rejection, and denial, removing the individual’s responsibility to act. Research suggests that, due to its unique observational obstacles in contemporary post-industrial societies, climate change is considered a psychologically distant event (Pawlik 559), one that is not personally salient due to the “perceived distance and remoteness [...] from one’s everyday experience” (O’Neill and Nicholson-Cole 370). In an examination of the barriers to behaviour change in the face of psychologically distant events, Robert Gifford argues that changing individuals’ perceptions of the issue-domain is one of the challenges of countering environmental inertia—the lack of initiative for environmentally sustainable social action (5). To challenge the status quo a radically different construction of the environment and the human-nature relationship is required to transform our perception of global environmental risks and ultimately result in environmentally consequential social action. Yann Arthus-Bertrand’s Home is a ritualised construction of contemporary environmental degradation and climate change which takes spectators on a rite of passage to a newfound understanding of the human-nature relationship. Transformation through re-imagining individuals’ roles, responsibilities, and practices is an intrinsic quality of rituals. A ritual charts a subjects path from one state of consciousness to the next, resulting in a meaningful change of attitudes (Deflem 8). Through a lifelong study of African rituals British cultural ethnographer Victor Turner refined his concept of rituals in a modern social context. Turner observed that rituals conform to a three-phased processural form (The Ritual Process 13–14). First, in the separation stage, the subjects are selected and removed from their fixed position in the social structure. Second, they enter an in-between and ambiguous liminal stage, characterised by a “partial or complete separation of the subject from everyday existence” (Deflem 8). Finally, imbued with a new perspective of the outside world borne out of the experience of reflexivity, liminality, and a cathartic cleansing, subjects are reintegrated into the social reality in a new, stable state. The three distinct stages make the ritual an emotionally charged, highly personal experience that “demarcates the passage from one phase to another in the individual’s life-cycle” (Turner, “Symbols” 488) and actively shapes human attitudes and behaviour. Adhering to the three-staged processural form of the ritual, Arthus-Bertrand guides spectators towards a newfound understanding of their roles and responsibilities in creating a desirable future. In the first stage—the separation—aerial photography of Home alienates viewers from their anthropocentric perspectives of the outside world. This establishes Earth as a body, and unearths spectators’ guilt and shame in relation to contemporary world risks. Aerial photography strips landscapes of their conventional qualities of horizon, scale, and human reference. As fine art photographer Emmet Gowin observes, “when one really sees an awesome, vast place, our sense of wholeness is reorganised [...] and the body seems always to diminish” (qtd. in Reynolds 4). Confronted with a seemingly infinite sublime landscape from above, the spectator’s “body diminishes” as they witness Earth’s body gradually taking shape. Home’s rushing rivers of Indonesia are akin to blood flowing through the veins and the Siberian permafrost seems like the texture of skin in extreme close-up. Arthus-Bertrand establishes a geocentric embodiment to force spectators to perceive and experience the environmental degradation brought about by the dominant social practices of contemporary post-industrial modernity. The film-maker visualises the maltreatment of the environment through suggested abuse of the Earth’s body. Images of industrial agricultural practices in the United States appear to leave scratches and scars on the landscape, and as a ship crosses the Arctic ice sheets of the Northwest Passage the boat glides like the surgeon’s knife cutting through the uppermost layer of the skin. But the deep blue water that’s revealed in the wake of the craft suggests a flesh and body now devoid of life, a suffering Earth in the wake of global climatic change. Arthus-Bertrand’s images become the sublime evidence of human intervention in the environment and the reflection of present-day industrialisation materially altering the face of Earth. The film-maker exploits spectators’ geocentric perspective and sensibility to prompt reflexivity, provide revelations about the self, and unearth the forgotten shame and guilt in having inadvertently caused excessive environmental degradation. Following the sequences establishing Earth as the body of the text Arthus-Bertrand returns spectators to their everyday “natural” environment—the city. Having witnessed and endured the pain and suffering of Earth, spectators now gaze at the skyscrapers standing bold and tall in the cityscape with disillusionment. The pinnacles of modern urban development become symbols of arrogance and exploitation: structures forced upon the landscape. Moreover, the images of contemporary cityscapes in Home serve as triggers for ritual reflexivity, allowing the spectator to “perceive the self [...] as a distanced ‘other’ and hence achieve a partial ‘self-transcendence’” (Beck, Comments 491). Arthus-Bertrand’s aerial photographs of Los Angeles, New York, and Tokyo fold these distinct urban environments into one uniform fusion of glass, metal, and concrete devoid of life. The uniformity of these cultural landscapes prompts spectators to add the missing element: the human. Suddenly, the homes and offices of desolate cityscapes are populated by none other than us, looking at ourselves from a unique vantage point. The geocentric sensibility the film-maker invoked with the images of the suffering Earth now prompt a revelation about the self as spectators see their everyday urban environments in a new light. Their homes and offices become blemishes on the face of the Earth: its inhabitants, including the spectators themselves, complicit in the excessive mistreatment of the planet. The second stage of the ritual allows Arthus-Bertrand to challenge dominant social paradigms of present day post-industrial societies and introduce new, alternative moral directives to govern our habits and attitudes. Following the separation, ritual subjects enter an in-between, threshold stage, one unencumbered by the spatial, temporal, and social boundaries of everyday existence. Turner posits that a subjects passage through this liminal stage is necessary to attain psychic maturation and successful transition to a new, stable state at the end of the ritual (The Ritual Process 97). While this “betwixt and between” (Turner, The Ritual Process 95) state may be a fleeting moment of transition, it makes for a “lived experience [that] transforms human beings cognitively, emotionally, and morally.” (Horvath et al. 3) Through a change of perceptions liminality paves the way toward meaningful social action. Home places spectators in a state of liminality to contrast geocentric and anthropocentric views. Arthus-Bertrand contrasts natural and human-made environments in terms of diversity. The narrator’s description of the “miracle of life” is followed by images of trees seemingly defying gravity, snow-covered summits among mountain ranges, and a whale in the ocean. Grandeur and variety appear to be inherent qualities of biodiversity on Earth, qualities contrasted with images of the endless, uniform rectangular greenhouses of Almeria, Spain. This contrast emphasises the loss of variety in human achievements and the monotony mass-production brings to the landscape. With the image of a fire burning atop a factory chimney, Arthus-Bertrand critiques the change of pace and distortion of time inherent in anthropocentric views, and specifically in contemporary modernity. Here, the flames appear to instantly eat away at resources that have taken millions of years to form, bringing anthropocentric and geocentric temporality into sharp contrast. A sequence showing a night time metropolis underscores this distinction. The glittering cityscape is lit by hundreds of lights in skyscrapers in an effort, it appears, to mimic and surpass daylight and thus upturn the natural rhythm of life. As the narrator remarks, in our present-day environments, “days are now the pale reflections of nights.” Arthus-Bertrand also uses ritual liminality to mark the present as a transitory, threshold moment in human civilisation. The film-maker contrasts the spectre of our past with possible visions of the future to mark the moment of now as a time when humanity is on the threshold of two distinct states of mind. The narrator’s descriptions of contemporary post-industrial society’s reliance on non-renewable resources and lack of environmentally sustainable agricultural practices condemn the past and warn viewers of the consequences of continuing such practices into the future. Exploring the liminal present Arthus-Bertrand proposes distinctive futurescapes for humankind. On the one hand, the narrator’s description of California’s “concentration camp style cattle farming” suggests that humankind will live in a future that feeds from the past, falling back on frames of horrors and past mistakes. On the other hand, the example of Costa Rica, a nation that abolished its military and dedicated the budget to environmental conservation, is recognition of our ability to re-imagine our future in the face of global risk. Home introduces myths to imbue liminality with the alternative dominant social paradigm of ecology. By calling upon deep-seated structures myths “touch the heart of society’s emotional, spiritual and intellectual consciousness” (Killingsworth and Palmer 176) and help us understand and come to terms with complex social, economic, and scientific phenomena. With the capacity to “pattern thought, beliefs and practices,” (Maier 166) myths are ideal tools in communicating ritual liminality and challenging contemporary post-industrial society’s dominant social paradigms. The opening sequence of Home, where the crescent Earth is slowly revealed in the darkness of space, is an allusion to creation: the genesis myth. Accompanied only by a gentle hum our home emerges in brilliant blue, white, and green-brown encompassing most of the screen. It is as if darkness and chaos disintegrated and order, life, and the elements were created right before our eyes. Akin to the Earthrise image taken by the astronauts of Apollo 8, Home’s opening sequence underscores the notion that our home is a unique spot in the blackness of space and is defined and circumscribed by the elements. With the opening sequence Arthus-Bertrand wishes to impart the message of interdependence and reliance on elements—core concepts of ecology. Balance, another key theme in ecology, is introduced with an allusion to the Icarus myth in a sequence depicting Dubai. The story of Icarus’s fall from the sky after flying too close to the sun is a symbolic retelling of hubris—a violent pride and arrogance punishable by nemesis—destruction, which ultimately restores balance by forcing the individual back within the limits transgressed (Littleton 712). In Arthus-Bertrand’s portrayal of Dubai, the camera slowly tilts upwards on the Burj Khalifa tower, the tallest human-made structure ever built. The construction works on the tower explicitly frame humans against the bright blue sky in their attempt to reach ever further, transgressing their limitations much like the ill-fated Icarus. Arthus-Bertrand warns that contemporary modernity does not strive for balance or moderation, and with climate change we may have brought our nemesis upon ourselves. By suggesting new dominant paradigms and providing a critique of current maxims, Home’s retelling of myths ultimately sees spectators through to the final stage of the ritual. The last phase in the rite of passage “celebrates and commemorates transcendent powers,” (Deflem 8) marking subjects’ rebirth to a new status and distinctive perception of the outside world. It is at this stage that Arthus-Bertrand resolves the emotional distress uncovered in the separation phase. The film-maker uses humanity’s innate capacity for creation and renewal as a cathartic cleansing aimed at reconciling spectators’ guilt and shame in having inadvertently exacerbated global environmental degradation. Arthus-Bertrand identifies renewable resources as the key to redeeming technology, human intervention in the landscape, and finally humanity itself. Until now, the film-maker pictured modernity and technology, evidenced in his portrayal of Dubai, as synonymous with excess and disrespect for the interconnectedness and balance of elements on Earth. The final sequence shows a very different face of technology. Here, we see a mechanical sea-snake generating electricity by riding the waves off the coast of Scotland and solar panels turning towards the sun in the Sahara desert. Technology’s redemption is evidenced in its ability to imitate nature—a move towards geocentric consciousness (a lesson learned from the ritual’s liminal stage). Moreover, these human-made structures, unlike the skyscrapers earlier in the film, appear a lot less invasive in the landscape and speak of moderation and union with nature. With the above examples Arthus-Bertrand suggests that humanity can shed the greed that drove it to dig deeper and deeper into the Earth to acquire non-renewable resources such as oil and coal, what the narrator describes as “treasures buried deep.” The incorporation of principles of ecology, such as balance and interconnectedness, into humanity’s behaviour ushers in reconciliation and ritual cleansing in Home. Following the description of the move toward renewable resources, the narrator reveals that “worldwide four children out of five attend school, never has learning been given to so many human beings” marking education, innovation, and creativity as the true inexhaustible resources on Earth. Lastly, the description of Antarctica in Home is the essence of Arthus-Bertrand’s argument for our innate capacity to create, not simply exploit and destroy. Here, the narrator describes the continent as possessing “immense natural resources that no country can claim for itself, a natural reserve devoted to peace and science, a treaty signed by 49 nations has made it a treasure shared by all humanity.” Innovation appears to fuel humankind’s transcendence to a state where it is capable of compassion, unification, sharing, and finally creating treasures. With these examples Arthus-Bertrand suggests that humanity has an innate capacity for creative energy that awaits authentic expression and can turn humankind from destroyer to creator. In recent years various risk communication texts have explicitly addressed climate change, endeavouring to instigate environmentally consequential social action. Home breaks discursive ground among them through its ritualistic construction which seeks to transform spectators’ perception, and in turn roles and responsibilities, in the face of global environmental risks. Unlike recent climate change media texts such as An Inconvenient Truth (2006), The 11th Hour (2007), The Age of Stupid (2009), Carbon Nation (2010) and Earth: The Operator’s Manual (2011), Home eludes simple genre classification. On the threshold of photography and film, documentary and fiction, Arthus-Bertrand’s work is best classified as an advocacy film promoting public debate and engagement with a universal concern—the state of the environment. The film’s website, available in multiple languages, contains educational material, resources to organise public screenings, and a link to GoodPlanet.info: a website dedicated to environmentalism, including legal tools and initiatives to take action. The film-maker’s approach to using Home as a basis for education and raising awareness corresponds to Antonio Lopez’s critique of contemporary mass-media communications of global risks. Lopez rebukes traditional forms of mediatised communication that place emphasis on the imparting of knowledge and instead calls for a participatory, discussion-driven, organic media approach, akin to a communion or a ritual (106). Moreover, while texts often place a great emphasis on the messenger, for instance Al Gore in An Inconvenient Truth, Leonardo DiCaprio in The 11th Hour, or geologist Dr. Richard Alley in Earth: The Operator’s Manual, Home’s messenger remains unseen—the narrator is only identified at the very end of the film among the credits. The film-maker’s decision to forego a central human character helps dissociate the message from the personality of the messenger which aids in establishing and maintaining the geocentric sensibility of the text. Finally, the ritual’s invocation and cathartic cleansing of emotional distress enables Home to at once acknowledge our environmentally destructive past habits and point to a hopeful, environmentally sustainable future. While The Age of Stupid mostly focuses on humanity’s present and past failures to respond to an imminent environmental catastrophe, Carbon Nation, with the tagline “A climate change solutions movie that doesn’t even care if you believe in climate change,” only explores the potential future business opportunities in turning towards renewable resources and environmentally sustainable practices. The three-phased processural form of the ritual allows for a balance of backward and forward-looking, establishing the possibility of change and renewal in the face of world risk. The ritual is a transformative experience. As Turner states, rituals “interrupt the flow of social life and force a group to take cognizance of its behaviour in relation to its own values, and even question at times the value of those values” (“Dramatic Ritual” 82). Home, a ritualised media text, is an invitation to look at our world, its dominant social paradigms, and the key element within that world—ourselves—with new eyes. It makes explicit contemporary post-industrial society’s dependence on the environment, highlights our impact on Earth, and reveals our complicity in bringing about a contemporary world risk. The ritual structure and the self-reflexivity allow Arthus-Bertrand to transform climate change into a personally salient issue. This bestows upon the spectator the responsibility to act and to reconcile the spectre of the past with the vision of the future.Acknowledgments The author would like to thank Dr. Angi Buettner whose support, guidance, and supervision has been invaluable in preparing this article. 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