Editorial: Remote Ischemic Conditioning (Pre, Per, and Post) as an Emerging Strategy of Neuroprotection in Ischemic Stroke

EDITORIAL articleThis study was funded by Carlos III Health Institute and cofunded by European Union (ERDF A way to make Europe) Project (PI17-01725) and the RICORS Research Network to FP, NIH Funding (R01 NS099455, 1UO1NS113356, and R01 NS112511) to DH, Italian Ministry of Health - PRIN 2017CY3J3W to SB. French National Minsitry of Health Grant 2014 AOR13032 to FP, TE is the Chief Investigator for the Remote ischaemic conditioning after stroke trial (RECAST), RECAST-2, and RECAST-3 funded through the NIHR Efficacy and Mechanism Evaluation (EME) Programme, Award ID NIHR128240

Horizontal gene transfer contributed to the evolution of extracellular surface structures

The single-cell layered ectoderm of the fresh water polyp Hydra fulfills the function of an epidermis by protecting the animals from the surrounding medium. Its outer surface is covered by a fibrous structure termed the cuticle layer, with similarity to the extracellular surface coats of mammalian epithelia. In this paper we have identified molecular components of the cuticle. We show that its outermost layer contains glycoproteins and glycosaminoglycans and we have identified chondroitin and chondroitin-6-sulfate chains. In a search for proteins that could be involved in organising this structure we found PPOD proteins and several members of a protein family containing only SWT (sweet tooth) domains. Structural analyses indicate that PPODs consist of two tandem β-trefoil domains with similarity to carbohydrate-binding sites found in lectins. Experimental evidence confirmed that PPODs can bind sulfated glycans and are secreted into the cuticle layer from granules localized under the apical surface of the ectodermal epithelial cells. PPODs are taxon-specific proteins which appear to have entered the Hydra genome by horizontal gene transfer from bacteria. Their acquisition at the time Hydra evolved from a marine ancestor may have been critical for the transition to the freshwater environment

Diasporas and secessionist conflicts : the mobilization of the Armenian, Albanian and Chechen diasporas

This article examines the impact of diasporas on secessionist conflicts, focusing on the Albanian, Armenian and Chechen diasporas and the conflicts in Kosovo, Karabakh and Chechnya during the 1990s. How do diasporas radicalize these conflicts? I argue that despite differences in diaspora communal characteristics and the types of the secessionist conflicts, a common pattern of mobilization develops. Large-scale diasporic support for secessionism emerges only after independence is proclaimed by the local elites. From that point onwards diasporas become engaged in a conflict spiral, and transnational coalitions are formed between local secessionist and diaspora groups. Depending on the organizational strength of the local strategic centre and the diasporic institutions, these coalitions endure or dissipate. Diasporas exert radicalization influences on the conflict spiral on two specific junctures – when grave violations of human rights occur in the homeland and when local moderate elites start losing credibility that they can achieve the secessionist goal

Biomarkers of rapid chronic kidney disease progression in type 2 diabetes.

Here we evaluated the performance of a large set of serum biomarkers for the prediction of rapid progression of chronic kidney disease (CKD) in patients with type 2 diabetes. We used a case-control design nested within a prospective cohort of patients with baseline eGFR 30-60 ml/min per 1.73 m(2). Within a 3.5-year period of Go-DARTS study patients, 154 had over a 40% eGFR decline and 153 controls maintained over 95% of baseline eGFR. A total of 207 serum biomarkers were measured and logistic regression was used with forward selection to choose a subset that were maximized on top of clinical variables including age, gender, hemoglobin A1c, eGFR, and albuminuria. Nested cross-validation determined the best number of biomarkers to retain and evaluate for predictive performance. Ultimately, 30 biomarkers showed significant associations with rapid progression and adjusted for clinical characteristics. A panel of 14 biomarkers increased the area under the ROC curve from 0.706 (clinical data alone) to 0.868. Biomarkers selected included fibroblast growth factor-21, the symmetric to asymmetric dimethylarginine ratio, β2-microglobulin, C16-acylcarnitine, and kidney injury molecule-1. Use of more extensive clinical data including prebaseline eGFR slope improved prediction but to a lesser extent than biomarkers (area under the ROC curve of 0.793). Thus we identified several novel associations of biomarkers with CKD progression and the utility of a small panel of biomarkers to improve prediction.We acknowledge all the SUMMIT partners (http://www.imi-summit.eu/) for their assistance with this project. This work was funded by the Innovative Medicine Initiative under grant agreement no. IMI/115006 (the SUMMIT consortium) and the Go-DARTS cohort was funded by the Chief Scientists Office Scotland.This is the accepted manuscript of a paper published in Kidney International (Looker et al., Kidney International, 2015 doi: 10.1038/ki.2015.199). The final version is available at http://dx.doi.org/10.1038/ki.2015.19

Human Rights and the War on Terror: Complete 2005 - 2007 Topical Research Digest

“9/11 changed everything.” Not really. In fact, there has been far more continuity than change over the past six years in both international and domestic politics. Nonetheless, human rights often have been harmed—although not by terrorism but by “the war on terror.

Cops, Teachers, and the Art of the Impossible: Explaining the lack of diffusion of impossible job innovations

In their now classic Impossible Jobs in Public Management, Hargrove and Glidewell (1990) argue that public agencies with limited legitimacy, high conflict, low professional authority, and weak agency myths have essentially impossible jobs. Leaders of such agencies can do little more than cope, which is also a theme of James Q. Wilson (1989), among others. Yet in the years since publication of Impossible Jobs, one such position, that of police commissioner has proven possible. Over a sustained 17-year period, the New York City Police Department has achieved dramatic reductions in crime with relatively few political repercussions, as described by Kelling and Sousa (2001). A second impossible job discussed by Wilson and also by Frederick Hess (1999), city school superintendent, has also proven possible, with Houston and Edmonton having considerable academic success educating disadvantaged children. In addition, Atlanta and Pittsburgh enjoyed significant success in elementary schooling, though the gains were short-lived for reasons we will describe. More recently, under Michelle Rhee, Washington D.C. schools have made the most dramatic gains among city school systems. These successes in urban crime control and public schooling have not been widely copied. Accordingly, we argue that the real conundrum of impossible jobs is why agency leaders fail to copy successful innovations. Building on the work of Teodoro (2009), we will discuss how the relative illegitimacy of clients and inflexibility of personnel systems combine with the professional norms, job mobility and progressive ambition of agency leaders to limit the diffusion of innovations in law enforcement and schooling. We will conclude with ideas about how to overcome these barriers

The Grizzly, November 12, 1991

Evaluations Show Drop in Pledge Grades • SAC Changes to AFAC • Voters Choose Wofford • Tri-Lamba Meets • Salk to Speak on Founders\u27 Day • Haley Visits Nearby High School • Crucible Captivates • WVOU at Music Marathon • Environmental Corner • Bench Art • Killer CAB Comedy • Fantasia • National Chemistry Week Unveils The Alchemist • Changing Life\u27s Blueprints • The Trouble With Wofford • The Black Hole of Greek Life • Face Off: Pros and Cons of GALA • Adopt a Flower Bed • IFC and The Illusion of Good Faith • Bears Squeak by King\u27s Point • Lady Bears Run Strong • Field Hockey Ends Season with a Tie • \u27Mers Submerge • Lady Swimmers Defeat Dickinsonhttps://digitalcommons.ursinus.edu/grizzlynews/1283/thumbnail.jp

Phase I/pharmacokinetic study of CCI-779 in patients with recurrent malignant glioma on enzyme-inducing antiepileptic drugs

Objectives : CCI-779 is an ester of the immunosuppressive agent sirolimus (rapamycin) that causes cell-cycle arrest at G1 via inhibition of key signaling pathways resulting in inhibition of RNA translation. Antitumor activity has been demonstrated using cell lines and animal models of malignant glioma. Patients receiving enzyme-inducing anti-epileptic drugs (EIAEDs) can have altered metabolism of drugs like CCI-779 that are metabolized through the hepatic cytochrome P450 enzyme system. The objectives of this study were to determine the pharmacokinetic profile and the maximum tolerated dose of CCI-779 in patients with recurrent malignant gliioma taking EIAEDs. Study design: The starting dose of CCI-779 was 250 mg intravenously (IV) administered weekly on a continuous basis. Standard dose escalation was performed until the maximum tolerated dose was established. Toxicity was assessed using the National Cancer Institute common toxicity criteria. Results : Two of 6 patients treated at the second dose level of 330 mg sustained a dose-limiting toxicity: grade III stomatitis, grade 3 hypercholesterolemia, or grade 4 hypertriglyceridemia. The maximum tolerated dose was reached at 250 mg IV. Pharmacokinetic profiles were similar to those previously described, but the area under the whole blood concentration-time curve of rapamycin was 1.6 fold lower for patients on EIAEDs. Conclusions : The recommended phase II dose of CCI 779 for patients on enzyme-inducing antiepileptic drugs is 250 mg IV weekly. A phase II study is ongoing to determine the efficacy of this agent.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/45250/1/10637_2004_Article_5273867.pd

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts