\u3ci\u3eUncle Tom’s Cabin\u3c/i\u3e in \u3ci\u3eThe National Era\u3c/i\u3e: Commentary on Chapter 1 and 2

In the first chapter of Uncle Tom’s Cabin, Stowe warns her readers that the “indulgence” of slave owners and the “affectionate loyalty” of the slaves themselves towards their masters have misled some observers to believe the “poetic legend” of slavery as a benevolent “patriarchal institution.” She does not deny the genuineness of these emotions, but she warns that “the shadow of a Law” makes a mockery of the human relationships that develop between masters and slaves: “So long as the law considers all these human beings, with beating hearts and living affections, only as so many things belonging to a master—so long as the failure, or misfortune, or imprudence, or death, of the kindest owner, may cause them any day to exchange a life of kind protection and indulgence for one of hopeless misery and toil, so long it is impossible to make anything beautiful or desirable in the best regulated administration of slavery.” We begin the novel, then, in what seems to be the model benevolent Shelby plantation in Kentucky, not the cruel Legree plantation in Louisiana, where the novel ends. Nevertheless, the “shadow of the law,” in the form of Mr. Shelby’s obligation to pay his debts, endangers the residents of the Shelby plantation. Stowe derived her portrait of slavery primarily from reading, not from direct experience and observation in the slave states of the South. She describes Eliza Harris as “not a fancy sketch, but taken from a remembrance, as we saw her years ago in Kentucky”—that is, during Stowe’s one brief trip South of the Mason-Dixon line during her years living in Cincinnati. Some white Southerners attacked Stowe for this lack of direct knowledge of the South and slavery. However, as historian William R. Taylor observed fifty years ago, what troubled them the most about Uncle Tom’s Cabin was not that she attacked their point of view, but that she understood it too well. As Taylor explains, beginning in the 1830s white Southerners invented the legend of “plantation paternalism,” “the image of sunshine and happiness around the plantation home,” to “justif[y] their peculiar institution to themselves and to others.”[1] Stowe only “[took] the Southerner at his word”: she did “not…deny the Southern defense of slavery but…suggested that it was inadequate, even if its claims were allowed.” Stowe set out to show, Taylor explains, that “kindness, generosity and affection provided no assurance against cruelty and brutality” and that “a slave could love his master and mistress and still wish to be free.”[2

Using Forums in Moodle to Provide Peer Feedback

In 2014, the Bloomsbury Learning Environment (BLE) Consortium initiated a wide-ranging, two-year-long research and dissemination project focusing on the use of technology in assessment and feedback. Our aim was to understand and improve processes, practices, opportunities and tools available to the institutional members of the BLE Consortium. From the project, we produced three research papers investigating current practice and 21 case studies describing both technology-enabled pedagogy and technical development. Now presented as a free ebook, co-edited by <strong>Leo Havemann</strong> and <strong>Sarah Sherman</strong>, we offer the flavour of the variety and breadth of the BLE’s activities relating to the project theme as a contribution to the education sector’s widening conversation about the interplay of assessment, feedback, pedagogy and technology

Effects of PPAR-β/-γ antagonists on nifedipine-mediated NO/cyclic-GMP formation and CD40L/sCD40L cascade.

<p>Platelets were incubated with various drugs, followed by addition of collagen. The levels of NOx (A) cyclic GMP formation (B) platelet surface CD40L expression (C) and sCD40L concentrations (D) were determined. Date were expressed as means ± SEM (<i>n</i> = 5). ^**<i>p</i> < 0.01, ^***<i>p</i> < 0.001 compared with collagen alone group; ⁺<i>p</i> < 0.05, ⁺⁺<i>p</i> < 0.01, ⁺⁺⁺<i>p</i> < 0.001 compared with respective collagen+nifedipine-treated group.</p

Mechanisms of Nifedipine-Downregulated CD40L/sCD40L Signaling in Collagen Stimulated Human Platelets

<div><p>The platelet-derived soluble CD40L (sCD40L) release plays a critical role in the development of atherosclerosis. Nifedipine, a dihydropyridine-based L-type calcium channel blocker (CCB), has been reported to have an anti-atherosclerotic effect beyond its blood pressure-lowering effect, but the molecular mechanisms remain unclear. The present study was designed to investigate whether nifedipine affects sCD40L release from collagen-stimulated human platelets and to determine the potential role of peroxisome proliferator-activated receptor-β/-γ (PPAR-β/-γ). We found that treatment with nifedipine significantly inhibited the platelet surface CD40L expression and sCD40L release in response to collagen, while the inhibition was markedly reversed by blocking PPAR-β/-γ activity with specific antagonist such as GSK0660 and GW9662. Meanwhile, nifedipine also enhanced nitric oxide (NO) and cyclic GMP formation in a PPAR-β/-γ-dependent manner. When the NO/cyclic GMP pathway was suppressed, nifedipine-mediated inhibition of sCD40L release was abolished significantly. Collagen-induced phosphorylation of p38MAPK, ERK1/2 and HSP27, matrix metalloproteinase-2 (MMP-2) expression/activity and reactive oxygen species (ROS) formation were significantly inhibited by nifedipine, whereas these alterations were all attenuated by co-treatment with PPAR-β/-γ antagonists. Collectively, these results demonstrate that PPAR-β/-γ-dependent pathways contribute to nifedipine-mediated downregulation of CD40L/sCD40L signaling in activated platelets through regulation of NO/ p38MAPK/ERK1/2/HSP27/MMP-2 signalings and provide a novel mechanism regarding the anti-atherosclerotic effect of nifedipine.</p></div

Hypothetical model of the signaling pathways of nifedipine-mediated reduction of sCD40L release from collagen-stimulated platelets.

<p>Nifedipine initially activates PPAR-β/-γ followed by increased formation of NO/cyclic GMP and down-regulation of p38MAPK/ERK1/2/HSP27 signaling as well as ROS generation, which then attenuates MMP-2 activity and ultimately inhibits sCD40L release from activated platelets.</p

Effects of PPAR-β/-γ antagonists on nifedipine-mediated phosphorylation of P38MAPK, ERK1/2 and HSP27.

<p>Platelets were pretreated with 5 μ M nifedipine or nifedipine combined with various drugs for 3 min followed by addition of collagen for 6 min. The expression of phospho-P38MAPK and total-P38MAPK (A), phospho-ERK1/2 and total ERK1/2 (B), phospho-HSP27 and total-HSP27 (C) were determined. Date were expressed as means ± SEM (<i>n</i> = 5). ^***<i>p</i> < 0.001 compared with collagen alone group; ⁺⁺<i>p</i> < 0.01, ⁺⁺⁺<i>p</i> < 0.001 compared with respective collagen+nifedipine-treated group.</p

Effects of nifedipine on the membrane CD40L expression and sCD40L release.

<p>Washed platelets were preincubated with various doses of nifedipine or nifedipine combined with GSK0660 (5 μ M) or GW9662 (5 μ M) for 3 min, followed by addition of collagen (10 μ g/ml) for 6 min. The platelet surface CD40L expression (A) and the levels of sCD40L (B) were determined. Data were presented as means ± SEM (<i>n</i> = 5). ^*<i>p</i> < 0.05, ^**<i>p</i> < 0.01, ^***<i>p</i> < 0.001 compared with the collagen alone group; ⁺<i>p</i> < 0.05, ⁺⁺<i>p</i> < 0.01, ⁺⁺⁺<i>p</i> < 0.001 compared with respective collagen+nifedipine-treated group.</p

Characteristics of surgical patients with renal dialysis and controls.^*

*<p>Renal dialysis: at least three times per week lasting more than three months for dialysis therapy within the 24-month preoperative period.</p><p>COPD, chronic obstructive pulmonary disease; CS, caesarean section.</p

The influence of FIR on the PI3K signaling pathway in HUVECs.

<p>(A) FIR exposure-influenced phosphatase and tensin homolog (PTEN) activity. HUVECs were treated with vascular endothelial growth factor (VEGF) (10 ng/ml) or FIR exposure as indicated for 30 min. PTEN activity in each sample was detected by PTEN Malachite Green Assay Kit. The relative level of FIR-induced PTEN activity is shown as the mean±S.D. from six experiments. (B) Western blotting of PI3K p85. GAPDH was detected as a loading control. (C) FIR exposure-induced RNA levels of PI3K p85. HUVECs were pretreated with FIR exposure for 30 min, and then cultured for the indicated periods. The mRNA quantity of PI3K in each sample was detected by a qPCR with specific primers for the PI3K subunits p85α and p85β. The relative mRNA level of FIR-induced PI3K is shown as the mean±S.D. from six experiments. C, control. * <i>p</i><0.05 vs. the control without FIR exposure.</p

Postoperative mortality and complications associated with hypertension or diabetes mellitus in surgical patients with preoperative regular dialysis.^*

*<p>Adjusted for age, sex, teaching hospital, coexisting disease and type of surgery and anesthesia.</p>†<p>The highest quintile of length of stay during the surgical admission (the patient percentage for each group belonged to the highest quintile of length of stay [≥18 days] of the total patients as percentage of increased length of stay).</p><p>OR, odds ratio; CI, confidence interval; ICU, intensive care unit.</p