Designing a Collaborative Blog about Student Success

The term “web log,” or “blog,” was first coined in 1997 by Jorn Barger (Blood). Blogs have been used in education as online journals, discussion platforms, course websites, and alternatives to mainstream media publications (EDUCAUSE, 2005). Two of the more common blogging platforms, Wordpress and Blogger , are relatively simple to use, requiring no knowledge of HTML to post entries. One of the many advantages of using blogs is that they can foster interaction among peers, thereby building community (EDUCAUSE, 2005; Richardson). For further explanation of how blogs work, Common Craft has created an easy-to-follow video entitled Blogs in Plain English

An Infinite Swapping Approach to the Rare-Event Sampling Problem

We describe a new approach to the rare-event Monte Carlo sampling problem. This technique utilizes a symmetrization strategy to create probability distributions that are more highly connected and thus more easily sampled than their original, potentially sparse counterparts. After discussing the formal outline of the approach and devising techniques for its practical implementation, we illustrate the utility of the technique with a series of numerical applications to Lennard-Jones clusters of varying complexity and rare-event character.Comment: 24 pages, 16 figure

Imatinib Reverses Doxorubicin Resistance by Affecting Activation of STAT3-Dependent NF-κB and HSP27/p38/AKT Pathways and by Inhibiting ABCB1

Despite advances in cancer detection and prevention, a diagnosis of metastatic disease remains a death sentence due to the fact that many cancers are either resistant to chemotherapy (conventional or targeted) or develop resistance during treatment, and residual chemoresistant cells are highly metastatic. Metastatic cancer cells resist the effects of chemotherapeutic agents by upregulating drug transporters, which efflux the drugs, and by activating proliferation and survival signaling pathways. Previously, we found that c-Abl and Arg non-receptor tyrosine kinases are activated in breast cancer, melanoma, and glioblastoma cells, and promote cancer progression. In this report, we demonstrate that the c-Abl/Arg inhibitor, imatinib (imatinib mesylate, STI571, Gleevec), reverses intrinsic and acquired resistance to the anthracycline, doxorubicin, by inducing G2/M arrest and promoting apoptosis in cancer cells expressing highly active c-Abl and Arg. Significantly, imatinib prevents intrinsic resistance by promoting doxorubicin-mediated NF-κB/p65 nuclear localization and repression of NF-κB targets in a STAT3-dependent manner, and by preventing activation of a novel STAT3/HSP27/p38/Akt survival pathway. In contrast, imatinib prevents acquired resistance by inhibiting upregulation of the ABC drug transporter, ABCB1, directly inhibiting ABCB1 function, and abrogating survival signaling. Thus, imatinib inhibits multiple novel chemoresistance pathways, which indicates that it may be effective in reversing intrinsic and acquired resistance in cancers containing highly active c-Abl and Arg, a critical step in effectively treating metastatic disease. Furthermore, since imatinib converts a master survival regulator, NF-κB, from a pro-survival into a pro-apoptotic factor, our data suggest that NF-κB inhibitors may be ineffective in sensitizing tumors containing activated c-Abl/Arg to anthracyclines, and instead might antagonize anthracycline-induced apoptosis

KEAP1 Is Required for Artesunate Anticancer Activity in Non-Small-Cell Lung Cancer

Artesunate is the most common treatment for malaria throughout the world. Artesunate has anticancer activity likely through the induction of reactive oxygen species, the same mechanism of action utilized in Plasmodium falciparum infections. Components of the kelch-like ECH-associated protein 1 (KEAP1)/nuclear factor erythroid 2-related factor 2 (NRF2) pathway, which regulates cellular response to oxidative stress, are mutated in approximately 30% of non-small-cell lung cancers (NSCLC); therefore, we tested the hypothesis that KEAP1 is required for artesunate sensitivity in NSCLC. Dose response assays identified A549 cells, which have a G333C-inactivating mutation in KEAP1, as resistant to artesunate, with an IC50 of 23.6 µM, while H1299 and H1563 cells were sensitive to artesunate, with a 10-fold lower IC50. Knockdown of KEAP1 through siRNA caused increased resistance to artesunate in H1299 cells. Alternatively, the pharmacological inhibition of NRF2, which is activated downstream of KEAP1 loss, by ML385 partially restored sensitivity of A549 cells to artesunate, and the combination of artesunate and ML385 was synergistic in both A549 and H1299 cells. These findings demonstrate that KEAP1 is required for the anticancer activity of artesunate and support the further development of NRF2 inhibitors to target patients with mutations in the KEAP1/NRF2 pathway

Numbers and narratives: How qualitative methods can strengthen the science of paediatric antimicrobial stewardship

Antimicrobial and diagnostic stewardship initiatives have become increasingly important in paediatric settings. The value of qualitative approaches to conduct stewardship work in paediatric patients is being increasingly recognized. This article seeks to provide an introduction to basic elements of qualitative study designs and provide an overview of how these methods have successfully been applied to both antimicrobial and diagnostic stewardship work in paediatric patients. A multidisciplinary team of experts in paediatric infectious diseases, paediatric critical care and qualitative methods has written a perspective piece introducing readers to qualitative stewardship work in children, intended as an overview to highlight the importance of such methods and as a starting point for further work. We describe key differences between qualitative and quantitative methods, and the potential benefits of qualitative approaches. We present examples of qualitative research in five discrete topic areas of high relevance for paediatric stewardship work: provider attitudes; provider prescribing behaviours; stewardship in low-resource settings; parents\u27 perspectives on stewardship; and stewardship work focusing on select high-risk patients. Finally, we explore the opportunities for multidisciplinary academic collaboration, incorporation of innovative scientific disciplines and young investigator growth through the use of qualitative research in paediatric stewardship. Qualitative approaches can bring rich insights and critically needed new information to antimicrobial and diagnostic stewardship efforts in children. Such methods are an important tool in the armamentarium against worsening antimicrobial resistance, and a major opportunity for investigators interested in moving the needle forward for stewardship in paediatric patients

Renal Volume Loss During Partial Nephrectomy Due to Resected Healthy Parenchyma: A Tool for Quick Estimation

Purpose: Our objective is to evaluate a technique for estimating the amount of healthy margin resected during partial nephrectomy (PN). Materials and Methods: The resected healthy margin volume was determined by planimetry (gold standard), which was performed in a prospective manner on 30 freshly resected renal masses by cross-sectional slicing every ∼5 mm. A single cross-sectional slice containing the largest tumor diameter (bivalved tumor) was chosen to build a model for estimating the amount of healthy kidney removed. This single-slice technique was then applied to a second series of patients (n = 39) status post PN. Three-dimensional models were created using pre- and postoperative CT scans to determine the overall volume loss following PN. Results: The median (range) for tumor diameter and tumor volume was 3.2 cm (1–6.1) and 10.7 cm3 (0.5–101.9), respectively, for the 30 PN specimens used to build the single-slice estimation equation. The median (range) healthy margin volume calculated by planimetry and single slice technique was 9.0 cm3 (1.0–22.1) and 7.8 cm3 (1.0–31.0), respectively (p = 0.37). The Pearson correlation was 0.84, and the median (range) percent difference between the planimetry and single slice techniques was −0.5% (−39% to 57%). For the 39 PN patients, the median (range) total renal volume loss, 25.8 cm3 (3–79), was significantly greater than the volume of healthy margin removed during resection, 5.7 cm3 (1–22), p < 0.001. Conclusions: The healthy margin resected during PN differs widely and can be estimated from a single cross-section. The healthy margin resected accounted for <50% of the total volume loss seen during PN

Natural variability and anthropogenic trends in oceanic oxygen in a coupled carbon cycle–climate model ensemble

Author Posting. © American Geophysical Union, 2009. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Global Biogeochemical Cycles 23 (2009): GB1003, doi:10.1029/2008GB003316.Internal and externally forced variability in oceanic oxygen (O2) are investigated on different spatiotemporal scales using a six-member ensemble from the National Center for Atmospheric Research CSM1.4-carbon coupled climate model. The oceanic O2 inventory is projected to decrease significantly in global warming simulations of the 20th and 21st centuries. The anthropogenically forced O2 decrease is partly compensated by volcanic eruptions, which cause considerable interannual to decadal variability. Volcanic perturbations in oceanic oxygen concentrations gradually penetrate the ocean's top 500 m and persist for several years. While well identified on global scales, the detection and attribution of local O2 changes to volcanic forcing is difficult because of unforced variability. Internal climate modes can substantially contribute to surface and subsurface O2 variability. Variability in the North Atlantic and North Pacific are associated with changes in the North Atlantic Oscillation and Pacific Decadal Oscillation indexes. Simulated decadal variability compares well with observed O2 changes in the North Atlantic, suggesting that the model captures key mechanisms of late 20th century O2 variability, but the model appears to underestimate variability in the North Pacific. Our results suggest that large interannual to decadal variations and limited data availability make the detection of human-induced O2 changes currently challenging.This study is supported by the EU projects CARBOOCEAN (511176-2) and EUROCEANS (511106-2) and the Swiss National Science Foundation

Crystal structure of the dynamin tetramer

The mechanochemical protein dynamin is the prototype of the dynamin superfamily of large GTPases, which shape and remodel membranes in diverse cellular processes. Dynamin forms predominantly tetramers in the cytosol, which oligomerize at the neck of clathrin-coated vesicles to mediate constriction and subsequent scission of the membrane. Previous studies have described the architecture of dynamin dimers, but the molecular determinants for dynamin assembly and its regulation have remained unclear. Here we present the crystal structure of the human dynamin tetramer in the nucleotide-free state. Combining structural data with mutational studies, oligomerization measurements and Markov state models of molecular dynamics simulations, we suggest a mechanism by which oligomerization of dynamin is linked to the release of intramolecular autoinhibitory interactions. We elucidate how mutations that interfere with tetramer formation and autoinhibition can lead to the congenital muscle disorders Charcot-Marie-Tooth neuropathy and centronuclear myopathy, respectively. Notably, the bent shape of the tetramer explains how dynamin assembles into a right-handed helical oligomer of defined diameter, which has direct implications for its function in membrane constriction