Shaper Nations: Stategies for a Changing World

Shaper Nations provides illuminating perspectives on the national strategies of eight emerging and established countries that are shaping global politics at the beginning of the twenty-first century. The volume’s authors offer a unique viewpoint: they live and work primarily in the country about which they write, bringing an insider’s feel for national debates and politics. The conventional wisdom on national strategy suggests that these states have clear central authority, coherently connect means to ends, and focus on their geopolitical environment. These essays suggest a different conclusion. In seven key countries―Brazil, China, Germany, India, Israel, Russia, and Turkey―strategy is dominated by nonstate threats, domestic politics, the distorting effect of history and national identity, economic development concerns, and the sheer difficulty, in the face of many powerful internal and external constraints, of pursuing an effective national strategy. The shapers represent a new trend in the international arena with important consequences. Among them is a more uncertain world in which countries concentrate on their own development rather than on shared problems that might divert precious resources, and attend more to regional than to global order. In responding to these shaper states, the United States must understand the sources of their national strategies in determining its own role on the global stage.https://scholarship.richmond.edu/bookshelf/1274/thumbnail.jp

Prospectus, December 10, 1980

HAPPY HOLIDAYS FROM PARKLAND COLLEGE; Pres. Staerkel sends greetings; Letters to the editor: Copy-editor raises questions, Volleyball coach resigns; Author of \u27Paper Lion,\u27 Plimpton lives nightmare; Construction of art gallery, remodeling planned at Parkland during new year; Star Wars, Digital Derby reflect technology in toys; Cobra men and women busy during holidays; Classifieds; Special Ed courses at Parkland next semester; Merry Christmas from the Prospectus; Sanders beats wife with poker, but life--and the soaps--go on; U of I holiday T.V., radio special to be on WCIA, WICD, and Cable; Concert Choir presents Gloria; Stroke Club to celebrate Dec. 13; Feature editor ready to \u27blow this thing\u27: Finals, deadlines just don\u27t mix with holiday cheer; Doomsday Schedule Fall, 1980; 50¢ charge for check cashing; REO\u27s \u27Hi Infidelity\u27 keeps pushin\u27 on; PC Community Band to give second concert; Three new courses offered in Spring \u2781; Christmas time...It makes you feel like a kid again: Merry Christmas!; Memories of 1980 fall semester; Prospectus Christmas Hide-A-Word; Christmas Personals; PC holiday certificate- perfect for anyone; Christmas magic seems special to parents of young children; PSI club to raffle radio; PC to offer Year-End Tax Planning Workshop; Science You Can See: The Christmas Star: A misinterpretation?; Looks, intelligence, money matter most (?); Get in the Holiday Spirit with mouth-watering aromas; Cobras beat Belleville; PC men whip John Logan: Offense comes alive; Patience pays off as Cobras beat Richland; Women\u27s Basketball 1980-81; Men\u27s Basketball 1980-81; National champ remains undecided; Balanced scoring paces Cobras; Defense, Defense, Defense....; Ingrum scores 31 to pace the Cobras: Cobras end Vols win streak at 20 games; Tom Smith is this week\u27s winner: After good start, Freddy hits major slump; Fast Freddy Contest; Bench Warmer: Cobra women even better than last yearhttps://spark.parkland.edu/prospectus_1980/1010/thumbnail.jp

Ion permeation and block of the gating pore in the voltage sensor of NaV1.4 channels with hypokalemic periodic paralysis mutations

Hypokalemic periodic paralysis and normokalemic periodic paralysis are caused by mutations of the gating charge–carrying arginine residues in skeletal muscle NaV1.4 channels, which induce gating pore current through the mutant voltage sensor domains. Inward sodium currents through the gating pore of mutant R666G are only ∼1% of central pore current, but substitution of guanidine for sodium in the extracellular solution increases their size by 13- ± 2-fold. Ethylguanidine is permeant through the R666G gating pore at physiological membrane potentials but blocks the gating pore at hyperpolarized potentials. Guanidine is also highly permeant through the proton-selective gating pore formed by the mutant R666H. Gating pore current conducted by the R666G mutant is blocked by divalent cations such as Ba2+ and Zn2+ in a voltage-dependent manner. The affinity for voltage-dependent block of gating pore current by Ba2+ and Zn2+ is increased at more negative holding potentials. The apparent dissociation constant (Kd) values for Zn2+ block for test pulses to −160 mV are 650 ± 150 µM, 360 ± 70 µM, and 95.6 ± 11 µM at holding potentials of 0 mV, −80 mV, and −120 mV, respectively. Gating pore current is blocked by trivalent cations, but in a nearly voltage-independent manner, with an apparent Kd for Gd3+ of 238 ± 14 µM at −80 mV. To test whether these periodic paralyses might be treated by blocking gating pore current, we screened several aromatic and aliphatic guanidine derivatives and found that 1-(2,4-xylyl)guanidinium can block gating pore current in the millimolar concentration range without affecting normal NaV1.4 channel function. Together, our results demonstrate unique permeability of guanidine through NaV1.4 gating pores, define voltage-dependent and voltage-independent block by divalent and trivalent cations, respectively, and provide initial support for the concept that guanidine-based gating pore blockers could be therapeutically useful

HpARI protein secreted by a helminth parasite suppresses interleukin-33

Infection by helminth parasites is associated with amelioration of allergic reactivity, but mechanistic insights into this association are lacking. Products secreted by the mouse parasite Heligmosomoides polygyrus suppress type 2 (allergic) immune responses through interference in the interleukin-33 (IL-33) pathway. Here, we identified H. polygyrus Alarmin Release Inhibitor (HpARI), an IL-33-suppressive 26-kDa protein, containing three predicted complement control protein (CCP) modules. In vivo, recombinant HpARI abrogated IL-33, group 2 innate lymphoid cell (ILC2) and eosinophilic responses to Alternaria allergen administration, and diminished eosinophilic responses to Nippostrongylus brasiliensis, increasing parasite burden. HpARI bound directly to both mouse and human IL-33 (in the cytokine's activated state) and also to nuclear DNA via its N-terminal CCP module pair (CCP1/2), tethering active IL-33 within necrotic cells, preventing its release, and forestalling initiation of type 2 allergic responses. Thus, HpARI employs a novel molecular strategy to suppress type 2 immunity in both infection and allergy. Osbourn et al identified HpARI, a protein secreted by a helminth parasite that is capable of suppressing allergic responses. HpARI binds to IL-33 (a critical inducer of allergy) and nuclear DNA, preventing the release of IL-33 from necrotic epithelial cells

A Functional Proteomic Method for Biomarker Discovery

The sequencing of the human genome holds out the hope for personalized medicine, but it is clear that analysis of DNA or RNA content alone is not sufficient to understand most disease processes. Proteomic strategies that allow unbiased identification of proteins and their post-transcriptional and -translation modifications are an essential complement to genomic strategies. However, the enormity of the proteome and limitations in proteomic methods make it difficult to determine the targets that are particularly relevant to human disease. Methods are therefore needed that allow rational identification of targets based on function and relevance to disease. Screening methodologies such as phage display, SELEX, and small-molecule combinatorial chemistry have been widely used to discover specific ligands for cells or tissues of interest, such as tumors. Those ligands can be used in turn as affinity probes to identify their cognate molecular targets when they are not known in advance. Here we report an easy, robust and generally applicable approach in which phage particles bearing cell- or tissue-specific peptides serve directly as the affinity probes for their molecular targets. For proof of principle, the method successfully identified molecular binding partners, three of them novel, for 15 peptides specific for pancreatic cancer

Genome-wide association meta-analysis in 269,867 individuals identifies new genetic and functional links to intelligence

Intelligence is highly heritable(1) and a major determinant of human health and well-being(2). Recent genome-wide meta-analyses have identified 24 genomic loci linked to variation in intelligence3-7, but much about its genetic underpinnings remains to be discovered. Here, we present a large-scale genetic association study of intelligence (n = 269,867), identifying 205 associated genomic loci (190 new) and 1,016 genes (939 new) via positional mapping, expression quantitative trait locus (eQTL) mapping, chromatin interaction mapping, and gene-based association analysis. We find enrichment of genetic effects in conserved and coding regions and associations with 146 nonsynonymous exonic variants. Associated genes are strongly expressed in the brain, specifically in striatal medium spiny neurons and hippocampal pyramidal neurons. Gene set analyses implicate pathways related to nervous system development and synaptic structure. We confirm previous strong genetic correlations with multiple health-related outcomes, and Mendelian randomization analysis results suggest protective effects of intelligence for Alzheimer's disease and ADHD and bidirectional causation with pleiotropic effects for schizophrenia. These results are a major step forward in understanding the neurobiology of cognitive function as well as genetically related neurological and psychiatric disorders.Peer reviewe

Factors Associated with Revision Surgery after Internal Fixation of Hip Fractures

Background: Femoral neck fractures are associated with high rates of revision surgery after management with internal fixation. Using data from the Fixation using Alternative Implants for the Treatment of Hip fractures (FAITH) trial evaluating methods of internal fixation in patients with femoral neck fractures, we investigated associations between baseline and surgical factors and the need for revision surgery to promote healing, relieve pain, treat infection or improve function over 24 months postsurgery. Additionally, we investigated factors associated with (1) hardware removal and (2) implant exchange from cancellous screws (CS) or sliding hip screw (SHS) to total hip arthroplasty, hemiarthroplasty, or another internal fixation device. Methods: We identified 15 potential factors a priori that may be associated with revision surgery, 7 with hardware removal, and 14 with implant exchange. We used multivariable Cox proportional hazards analyses in our investigation. Results: Factors associated with increased risk of revision surgery included: female sex, [hazard ratio (HR) 1.79, 95% confidence interval (CI) 1.25-2.50; P = 0.001], higher body mass index (fo

A Statistical Method for Circulation Analysis

published or submitted for publicatio