DataSheet1_Carbon emission reductions, pricing and social welfare of three-echelon supply chain considering consumer environmental awareness under carbon tax policy.docx

With the rapid growth in carbon emissions from transport, reducing these emissions is becoming as important as reducing emissions from production. We took a transporter as a member of the supply chain system and constructed a three-echelon supply chain composed of a manufacturer, transporter, and retailer. This study applies the Stackelberg game and Nash game to research the optimal carbon emission reductions, pricing, and social welfare when the government imposes a carbon tax on carbon emitters and consumers are environmentally conscious. The four scenarios were designed as follows: 1) non-cooperative decision-making (NN model), in which neither carbon emission reduction cooperation nor pricing cooperation takes place; 2) local-cooperative decision-making Ⅰ (CN model), in which only cooperation in the field of carbon emission reductions takes place; 3) local-cooperative decision-making Ⅱ (NC model), in which cooperation in the field of pricing without cooperation in the area of carbon emission reductions takes place; and 4) overall-cooperative decision-making (CC model), in which both cooperation in the field of carbon emission reductions and cooperation in the area of pricing take place. The results show that economic (as profit of the supply chain system), social (as pricing and social welfare), and environmental benefits (as the optimal carbon emission reductions) for the three-echelon supply chain will improve with the deepening of cooperation among the supply chain members. Carbon tax policies have different impacts on clean and polluting supply chains. High carbon tax can encourage clean supply chain to increase carbon emission reduction, but will lead to the reduction of carbon emission of polluting supply chain. A cross-shareholding contract is designed to coordinate the supply chain and achieve the optimal state of the overall cooperative decision. Finally, the paper provides suggestions on carbon emission reductions for enterprises and policymaking for the government.</p

Increased Arf6-GTP elevates Nox4 through Erk1/2 in Ang II-treated human podocyte.

Human podocytes were treated with 1 μM of angiotensin II (Ang II) for 24 h in the absence or presence of 10 μM of secinH3 (SH3). A. The levels of Nox4 were evaluated and compared. Data are presented as mean ± SD. n = 3. *p .01 vs. CTL, #p .05 vs. Ang II. B. Indirect immunofluorescence staining was performed for Nox4 (green color). The secondary antibody Alexa 488-conjugated goat anti-rabbit antibody alone was used for the blank control (A488 only). Magnification x 20. C. The activation level of Erk1/2 was assessed using immunoblot assay. Data are presented as mean ± SD. n = 3. *p .01 vs. 0 h. D. Human podocytes were pretreated for 1 h with the Erk1/2 inhibitor LY3214996 (1 μM; LY), and then Ang II was added at the final concentration of 1 μM and incubated for 24 h in the presence of 1 μM of LY3214996. The protein levels of Nox4 were evaluated. Data are presented as mean ± SD. n = 3. *p .01 vs. AngII-0min, #p S4 Fig.</p

Arf6 is related to Ang II-induced human podocyte injury.

A. Human podocytes were treated with angiotensin II (Ang II) as indicated. Apoptosis was evaluated with caspase 3 activity. Data are presented as mean ± SD. n = 5. *p .01 vs. 0 h or as indicated comparison. B and C. Human podocytes were treated with 1 μM of Ang II for 12, 24 and 48 h, respectively. The mRNA (B) and protein (C) levels of Arf6 was assessed and compared. Data are presented as mean ± SD. n = 3. *p S1 Fig. D. Human podocytes were treated with 1 μM of Ang II for 24 h, and indirect immunofluorescence was performed for Arf6 staining (green color). The non-treated cells were used as the controls (CTL). The 2nd antibody only was used for the blank control. Magnification x 40.</p

Angiotensin II promotes podocyte injury by activating Arf6-Erk1/2-Nox4 signaling pathway

Angiotensin II (Ang II) is a key contributor to glomerular disease by predominantly resulting in podocyte injury, whereas the underlying molecular mechanisms has not been fully understood. This study aimed to investigate if and how ADP-ribosylation factor 6 (Arf6), a small GTP-binding protein, involves Ang II-induced cellular injury in cultured human podocytes. Cellular injury was evaluated with caspase 3 activity, reactive oxygen species (ROS) level and TUNEL assay. Arf6 activity was measured using an Arf6-GTP Pull-Down Assay. Ang II significantly enhanced Arf6 expressions accompanied by increase of Arf6-GTP. The TUNEL-positive cells as well as activated caspase 3, NADPH oxidase 4 protein (Nox4) and ROS levels were dramatically increased in Ang II-treated podocytes, which was prevented by secinH3, an Arf6 activity inhibitor. Induction of ROS by Ang II was inhibited in podocytes with Nox4 knockdown. Ang II-induced elevation of Nox4 and ROS was prevented by Arf6 knockdown. Phpspho-Erk1/2Thr202/Tyr204 levels were upregulated remarkably following Ang II treatment, and Erk inhibitor LY3214996 significantly downregulated Nox4 expression. In addition, Ang II decreased CD2AP expression. Overexpression of CD2AP prevented Ang II-induced upregulation of Arf6-GTP. Our data demonstrated that Ang II promotes ROS production and podocytes injury through activation of Arf6-Erk1/2-Nox4 signaling. We also provided evidence that Ang II activates Arf6 by degradation of CD2AP.</div

Ang II increases ROS production through Arf6 in human podocytes.

A. Human podocytes were treated with 1 μM of angiotensin II (Ang II) for 12, 24 and 48 h, respectively. The ROS levels were measured using DCF assay and compared. Data are presented as mean ± SD. n = 6. *p .01 vs. 0 h. B. Human podocytes were treated with 1 μM of Ang II for 24 h in the absence or presence of 10 μM of secinH3 (SCH3). The non-treated cell was used as the controls (CTL). The ROS levels were measured and compared. Data are presented as mean ± SD. n = 6. *p .01 vs. CTL, #p .05 vs. Ang II.</p

Codes for reflective journals.

This mixed methods sequential explanatory study identified and explained the features of engagement strategies for MOOC forum discussion that help low-achieving students make significant progress. Triangulated data were collected from MOOC learners’ (n = 335) scores in two reading assessments, their posts to the embedded online discussion forum, and their self-reflection learning journals. Based on learning progress between pre- and post-assessment tasks, MOOC learners are divided into three groups: 1) little, 2) moderate, and 3) significant progress. According to a statistical analysis of the quantified posts, surprisingly, the low-scoring students from the pre-test who demonstrated significant progress later engaged in significantly fewer peer-peer and peer-teacher interactions in the online discussion forum. Guided by self-efficacy literature, the reflective journals of these learners suggested that 1) learner-content interactions may help them advance learning and obtain new information and linguistic knowledge from the peer-made learning materials in the discussion forum; 2) they did not share and exchange ideas and answers with their peers. Instead, they prefer learning from others’ discussions and wish to get quick feedback and suggestions on their contributions to the discussion forum; and 3) peer-peer and peer-teacher interactions were proposed as two solutions to regulate their online learning experience as they lack self-discipline and time-management skills. Implications include teachers’ continuous support to encourage low-achieving students to learn peer-generated content and quick feedback on their contributions to the discussion forum.</div

Ang II increases ROS production through Nox4 in human podocyte.

A. Human podocytes were treated with 1 μM of angiotensin II (Ang II) for 12, 24, and 48 h, and the protein levels of Nox4 were assessed and compared. Data are presented as mean ± SD. n = 3. *p .01 vs. 0 h. B and C. Podocytes stably expressing siRNA-Nox4 (siNox4) or siRNA-control (siCTL) were treated with 1 μM of Ang II for 24 h. The non-treated podocytes were used as the controls (CTL). The protein levels of Nox4 (B) and the ROS (C) were assessed and compared. Data are presented as mean ± SD. n = 3 (B) and 6 (C). *p .01 vs. CTL, #p .05 vs. Ang II or Ang II + siCTL. D and E. Podocytes were transduced with 15 μl of lentiviral shRNA-Arf6 (shArf6) and the control shRNA (shCTL), respectively. The non-treated cells were used as the controls (CTL). The protein levels of Nox4 and Arf6 (D) and the ROS level (E) were assessed. Data are presented as mean ± SD. n = 3 (D) and 4 (E). *p .01 vs. CTL, #p .05 vs. Ang II or Ang II + shCTL. Full length blots of A, B and D are provided in S3 Fig.</p

Ang II increases Arf6 activity through downregulation of CD2AP.

Human podocytes were treated with 1 μM of angiotensin II (Ang II) for 12, 24 and 48 h. A. The protein levels of CD2AP were assessed using immunoblot assay. Data are presented as mean ± SD. n = 3. *p .01 vs. 0 h. B-E. Human podocytes were transfected with pcDNA3.1CD2AP and pcDNA3.1 blank vector, respectively. 24 h later, 1 μM of Ang II was added and incubated for 24 h. The expressions of CD2AP (B) and the levels of ROS (C), Arf6-GTP (D), and apoptosis (E) were evaluated and compared. Data are presented as mean ± SD. n = 3 (B and D) and 4 (C and E). *p .05 vs. CTL, #p S5 Fig.</p

Arf6 involves Ang II-induced human podocyte injury.

A. Human podocytes were treated with 1 μM of angiotensin II (Ang II) for 12, 24 and 48 h, respectively. The levels of Arf6-GTP and total Arf6 were analyzed and compared. GTP-γs and GDP treated samples were used as the positive and negative control, respectively. Data are presented as mean ± SD. n = 3. *p .01 vs. 0 h. B and C. Human podocytes were treated with Ang II for 24 h in the absence or presence of secinH3 (SH3). The non-treated cell was used as the controls (CTL). The levels of Arf6-GTP and total Arf6 were analyzed and compared (B). The effect of 10 μM of secinH3 was evaluated on caspase 3 activity in Ang II-treated podocytes (C). Data are presented as mean ± SD. n = 5. *p .001 vs. CTL, #p .05 vs. Ang II. D. Human podocytes were treated with Ang II for 24 h in the absence or presence of secinH3 (10 μM), losartan (1 μM) and v-ZAD-fmk (10 μM). The vehicle DMSO treated cells were used as the controls (CTL). TUNEL assay was performed for evaluation of apoptotic cell death (arrows). Data are presented as mean ± SD. n = 4. *p .01 vs. CTL, #p .01 vs. Ang II. Magnification x 10. Full length blots of A and B are provided in S2 Fig.</p

Descriptive data.

This mixed methods sequential explanatory study identified and explained the features of engagement strategies for MOOC forum discussion that help low-achieving students make significant progress. Triangulated data were collected from MOOC learners’ (n = 335) scores in two reading assessments, their posts to the embedded online discussion forum, and their self-reflection learning journals. Based on learning progress between pre- and post-assessment tasks, MOOC learners are divided into three groups: 1) little, 2) moderate, and 3) significant progress. According to a statistical analysis of the quantified posts, surprisingly, the low-scoring students from the pre-test who demonstrated significant progress later engaged in significantly fewer peer-peer and peer-teacher interactions in the online discussion forum. Guided by self-efficacy literature, the reflective journals of these learners suggested that 1) learner-content interactions may help them advance learning and obtain new information and linguistic knowledge from the peer-made learning materials in the discussion forum; 2) they did not share and exchange ideas and answers with their peers. Instead, they prefer learning from others’ discussions and wish to get quick feedback and suggestions on their contributions to the discussion forum; and 3) peer-peer and peer-teacher interactions were proposed as two solutions to regulate their online learning experience as they lack self-discipline and time-management skills. Implications include teachers’ continuous support to encourage low-achieving students to learn peer-generated content and quick feedback on their contributions to the discussion forum.</div