R2P ten years after the World Summit: Explaining ongoing contestation over Pillar III

This article examines how and why contrasting interpretations of the international community’s role in preventing and responding to mass atrocity crimes continue to exist a decade after the Responsibility to Protect (R2P) was unanimously endorsed at the 2005 World Summit. Building on recent critical constructivist insights into the fluid, dynamic nature of norms, it advances two main arguments. The first is that continuing contestation over R2P’s third pillar is a product of a combination of internal and external sources of norm dynamism. R2P’s inherently complex normative structure, coupled with several external factors, including the broader normative environment, norm implementation experiences and a shift in global power towards the BRICS, have contributed to a period of renewed contestation and triggered attempts to re-formulate R2P thorough Brazil’s ‘Responsibility while Protecting’ (RwP) proposal and China’s semi-official ‘Responsible Protection’ concept. The second central argument is that such contestation is affecting R2P’s distinct normative prescriptions in different ways. While resistance to the implementation of coercive pillar III measures is currently impeding the normative progress of that component of the norm, this contestation has not prevented consensual pillar II assistance from becoming more deeply embedded in international practice and discourse.

Dissection of class III major histocompatibility complex haplotypes associated with rheumatoid arthritis

Objective. We have previously identified a single-nucleotide polymorphism (SNP) haplotype involving the lymphotoxin α (LTA) and tumor necrosis factor (TNF) loci (termed haplotype LTA-TNF2) on chromosome 6 that shows differential association with rheumatoid arthritis (RA) on HLA-DRB1*0404 and *0401 haplotypes, suggesting the presence of additional non-HLA-DRB1 RA susceptibility genes on these haplotypes. To refine this association, we performed a case-control association study using both SNPs and microsatellite markers in haplotypes matched either for HLA-DRB1*0404 or for HLA-DRB1*0401. Methods. Fourteen SNPs lying between HLA-DRB1 and LTA were genotyped in 87 DRB1*04-positive families. High-density microsatellite typing was performed using 24 markers spanning 2,500 kb centered around the TNF gene in 305 DRB1*0401 or *0404 cases and 400 DRB1*0401 or *0404 controls. Single-marker, 2-marker, and 3-marker minihaplotypes were constructed and their frequencies compared between the DRB1*0401 and DRB1*0404 matched case and control haplotypes. Results. Marked preservation of major histocompatibility complex haplotypes was seen, with chromosomes carrying LTA-TNF2 and either DRB1*0401 or DRB1*0404 both carrying an identical SNP haplotype across the 1-Mb region between TNF and HLA-DRB1. Using microsatellite markers, we observed two 3-marker minihaplotypes that were significantly overrepresented in the DRB1*0404 case haplotypes (P = 0.00024 and P = 0.00097). Conclusion. The presence of a single extended SNP haplotype between LTA-TNF2 and both DRB1*0401 and DRB1*0404 is evidence against this region harboring the genetic effects in linkage disequillbrium with LTA-TNF2. Two RA-associated haplotypes on the background of DRB1*0404 were identified in a 126-kb region surrounding and centromeric to the TNF locus.

Fine mapping of the MHC Class III region demonstrates association of AIF1 and rheumatoid arthritis

Objective. The heritability of RA has been estimated to be ∼55%, of which the MHC contributes about one-third. HLA-DRB1 alleles are strongly associated with RA, but it is likely that significant non-DRB1 MHC genetic susceptibility factors are involved. Previously, we identified two three-marker haplotypes in a 106-kb region in the MHC class III region immediately centromeric to TNF, which are strongly associated with RA on HLA-DRB1*0404 haplotypes. In the present study, we aimed to refine these associations further using a combination of genotyping and gene expression studies. Methods. Thirty-nine nucleotide polymorphisms (SNPs) were genotyped in 95 DRB1*0404 carrying unrelated RA cases, 125 DRB1*0404 - carrying healthy controls and 87 parent-case trio RA families in which the affected child carried HLA-DRB1*04. Quantitative RT-PCR was used to assess the expression of the positional candidate MHC class III genes APOM, BAT2, BAT3, BAT4, BAT5, AIF1, C6orf47, CSNK2β and LY6G5C, and the housekeeper genes, hypoxanthine-guanine phosphoribosyltransferase (HPRT) and β2-microglobulin (B2M) in 31 RA cases and 21 ethnically, age- and sex-matched healthy controls. Synovial membrane specimens from RA, PsA and OA cases were stained by an indirect immunoperoxidase technique using a mouse-anti-human AIF1 monoclonal antibody. Results. Association was observed between RA and single markers or two marker haplotypes involving AIF1, BAT3 and CSNK. AIF1 was also significantly overexpressed in RA mononuclear cells (1.5- to 1.9-fold difference, P = 0.02 vs HPRT, P = 0.002 vs B2M). AIF1 protein was clearly expressed by synovial macrophages in all the inflammatory synovial samples in contrast to the non-inflammatory OA samples. Conclusions. The results of the genotyping and expression studies presented here suggest a role for AIF1 in both the aetiology and pathogenesis of RA.

An asymmetric homodinuclear complex containing the mu-x-oxobis(mu-x-carboxylato)diruthenium(III) core: X-ray structure of [Ru20(o2ec6H4-p-OMe)3(en) (PPh3)2] (C104)" 3CHC13

Asymmetric tri-bridged diruthenium(III) complexes, [Ru2O(O(2)CR)(3)(en) (PPh(3))(2)](ClO4) (R = C6H4-p-X: X = OMe (1a), Me (1b); en=1,2-diaminoethane), were prepared and structurally characterized. Complex 1a 3CHCl(3), crystallizes in the triclinic space group P (1) over bar with a = 14.029(5), b = 14.205(5), c = 20.610(6) Angstrom, alpha= 107.26(3), beta = 101.84(3), gamma= 97.57(3)degrees, V= 3756(2) Angstrom(3) and Z = 2. The complex has an {Ru-2(mu-O)(mu-O(2)CR)(2)(2+)} core and exhibits [O4PRu(mu-O)RuPO2N2](+) coordination environments for the metal centers. The novel structural feature is the asymmetric arrangement of ligands at the terminal sites of the core which shows an Ru... Ru separation of 3.226(3) Angstrom and an Ru-O-Ru angle of 119.2(5)degrees. An intense visible band observed near 570 nm is assigned to a charge transfer transition involving the d pi-Ru(III) and p pi-mu-O Orbitals. Cyclic voltammetry of the complexes displays a reversible Ru-2(III,III) reversible arrow Ru-2(III,IV) couple near 0.8 V (versus SCE) in MeCN-0.1 M TBAP.

Axial binding of 2-methylimidazole to the tetraarylcarboxylatodiruthenium (II, III) core: X-ray crystal structure of [Ru-2(O2CC6H4-p-OMe)(4)(2-mimH)(2)](ClO4). 1.75CH(2)Cl(2).H2O

Diruthenium (II. III) complexes of the type [Ru-2(O2CAr)(4) (2-mimH)(2)](ClO4) (Ar = C6H4-p-X : X=OMe,1, X=Me, 2, 2-mimH=2-methylimidazole) have been isolated from the reaction of Ru2Cl(O2CAr)(4) with 2-mimH in CH2Cl2 followed by the addition of NaClO4. The crystal structure of 1.1.75CH(2)Cl(2).H2O has been determined. The crystal belongs to the monoclinic space group p2(1)/c with the following unit cell dimensions for the C40H40N4O16ClRu2.1.75CH(2)Cl(2).H2O (M = 1237.0) : a = 12.347(3)Angstrom, b = 17.615(5)Angstrom, c = 26.148(2)Angstrom,beta = 92.88(1)degrees. v = 5679(2)Angstrom(3). Z=4, D-c = 1.45 g cm(-3). lambda(Mo-K-alpha) = 0.7107 Angstrom, mu(Mo-K-alpha) = 8.1 cm(-1), T = 293 K, R = 0.0815 (wR(2) = 0.2118) for 5834 reflections with 1 > 2 sigma(I). The complex has a tetracarboxylatodiruthenium (II, III) core and two axially bound 2-methylimidazole ligands. The Ru-Ru bond length is 2.290(1)Angstrom. The Ru-Ru bond order is 2.5 and the complex is three-electron paramagnetic. The complex shows an irreversible Ru-2(II,III)-->Ru-2(Il,II) reduction near -0.2 V vs SCE in CH2Cl2-0. 1 MTBAP. The complexes exemplify the first adduct of the tetracarboxylatodiruthenium (II,III) core having N-donor ligands

Localisation of Plasmodium falciparum uroporphyrinogen III decarboxylase of the heme-biosynthetic pathway in the apicoplast and characterisation of its catalytic properties

Uroporphyrinogen decarboxylase (UROD) is a key enzyme in the heme-biosynthetic pathway and in Plasmodium falciparum it occupies a strategic position in the proposed hybrid pathway for heme biosynthesis involving shuttling of intermediates between different subcellular compartments in the parasite. In the present study, we demonstrate that an N-terminally truncated recombinant P. falciparum UROD (r(Δ)PfUROD) over-expressed and purified from Escherichia coli cells, as well as the native enzyme from the parasite were catalytically less efficient compared with the host enzyme, although they were similar in other enzyme parameters. Molecular modeling of PfUROD based on the known crystal structure of the human enzyme indicated that the protein manifests a distorted triose phosphate isomerase (TIM) barrel fold which is conserved in all the known structures of UROD. The parasite enzyme shares all the conserved or invariant amino acid residues at the active and substrate binding sites, but is rich in lysine residues compared with the host enzyme. Mutation of specific lysine residues corresponding to residues at the dimer interface in human UROD enhanced the catalytic efficiency of the enzyme and dimer stability indicating that the lysine rich nature and weak dimer interface of the wild-type PfUROD could be responsible for its low catalytic efficiency. PfUROD was localised to the apicoplast, indicating the requirement of additional mechanisms for transport of the product coproporphyrinogen to other subcellular sites for its further conversion and ultimate heme formation.

Antithrombin III associated with fibrinogen predicts the risk of cerebral ischemic stroke

Background and purpose: The purpose of this study is to examine the feasibility of developing plasma predictive value biomarkers of cerebral ischemic stroke before imaging evidence is acquired. Methods: Blood samples were obtained from 198 patients who attended our neurology department as emergencies - with symptoms of vertigo, numbness, limb weakness, etc. - within 4.5 h of symptom onset, and before imaging evidence was obtained and medical treatment. After the final diagnosis was made by MRI/DWI/MRA or CTA in the following 24-72 h, the above cases were divided into two groups: stroke group and non-stroke group according to the imaging results. The levels of baseline plasma antithrombin III (AT-III), thrombin-antithrombin III (TAT), fibrinogen, D-dimer and high-sensitivity C-reactive protein (hsCRP) in the two groups were assayed. Results: The level of the baseline AT-III in the stroke group was 118.07 ± 26.22%, which was lower than that of the non-stroke group (283.83 ± 38.39%). The levels of TAT, fibrinogen, hsCRP were 7.24 ± 2.28 μg/L, 5.49 ± 0.98 g/L, and 2.17 ± 1.07 mg/L, respectively, which were higher than those of the non-stroke group (2.53 ± 1.23 μg/L, 3.35 ± 0.50 g/L, 1.82 ± 0.67 mg/L). All the P-values were less than 0.001. The D-dimer level was 322.57 ± 60.34 μg/L, which was slightly higher than that of the non-stroke group (305.76 ± 49.52 μg/L), but the P-value was 0.667. The sensitivities of AT-III, TAT, fibrinogen, D-dimer and hsCRP for predicting ischemic stroke tendency were 97.37%, 96.05%, 3.29%, 7.89%, but the specificity was 93.62%, 82.61%, 100% and 100%, respectively, and all the P-values were less than 0.001. High levels of D-dimer and hsCRP were mainly seen in the few cases with severe large-vessel infarction. Conclusions: Clinical manifestations of acute focal neurological deficits were associated with plasma AT-III and fibrinogen. These tests might help the risk assessment of acute cerebral ischemic stroke and/or TIA with infarction tendency in the superacute stage before positive imaging evidence is obtained.

Synthesis, crystal structures and protease activity of amino acid Schiff base iron(III) complexes

Iron(III) complexes, (NHEt3)[Fe(III)(sal-met)(2)] and (NHEt3)[Fe(III)(sal-phe)(2)], of amino acid Schiffbase ligands, viz., N-salicylidene-L-methionine and N-salicylidene L-phenylalanine, have been prepared and their binding to bovine serum albumin (BSA) and photo-induced BSA cleavage activity have been investigated. The complexes are structurally characterized by single crystal X-ray crystallography. The crystal Structures of the discrete mononuclear rnonoanionic complexes show FeN2O4 octahedral coordination geometry in which the tridentate dianionic amino acid Schiff base ligand binds through phenolate and carboxylate oxygen and imine nitrogen atoms. The imine nitrogen atoms are trans to each other. The Fe-O and Fe-N bond distances range between 1.9 and 2.1 angstrom. The sal-met complex has two pendant thiomethyl groups. The high-spin iron(III) complexes (mu(eff) similar to 5.9 mu(B)) exhibit quasi-reversible Fe(III)/Fe(II) redox process near -0.6 V vs. SCE in water. These complexes display a visible electronic hand near 480 nm in tris-HCl buffer assignable to the phenolate-to-iron(III) charge transfer transition. The water soluble complexes bind to BSA giving binding constant values of similar to 10(5) M-1. The Complexes show non-specific oxidative cleavage of BSA protein on photo-irradiation with UV-A light of 365 nm.

Adsorption isotherms for neutral organic compounds-A hierarchy in modelling: Part III

A simple three-state model permitting two different configurational states for the solvent, together with one for the organic adsorbate, is analysed to derive the adsorption isotherm. The implications of this model regarding pseudo-two-state and pseudo-Frumkin adsorption isotherms are indicated. A critique of the earlier theory of Bockris, Devanathan and Müller is presented in brief.

Effect of chelating anions on metal-crown interaction. Part III. X-ray structure of potassium picrate complex of benzo-15-crown-5

The cr~¢stal structure of [potassium(benzo-15-crown-5)](picrate) shows that in the complex the metal is sandwiched between two crowns andhas no interaction with plcrate.

Gustaf III inför sina undersåtar : Konsten att härska och politikens kulturhistoria

The dissertation analyses the political culture of Sweden during the reign of King Gustav III (1771-1792). This period commonly referred to as the Gustavian era followed the so-called Age of Liberty ending half a century of strong parliamentary rule in Sweden. The question at the heart of this study engages with the practice of monarchical rule under Gustav III, its ideological origins and power-political objectives as well as its symbolic expression. The study thereby addresses the very nature of kingship. In concrete terms, why did Gustav III, his court, and his civil service vigorously pursue projects that contemporaneous political opponents and, in particular, subsequent historiography have variously pictured as irrelevant, superficial, or as products of pure vanity? The answer, the study argues, is to be found in patterns of political practice as developed and exercised by Gustav III and his administration, which formed a significant part of the political culture of Gustavian Sweden. The dissertation is divided into three parts. The first traces the use and development of royal graces chivalric orders, medals, titles, privileges, and other gifts issued by the king. The practice of royal reward is illustrated through two case studies: the 1772 coup d état that established Gustav III s rule, and the birth and baptism of the crown prince, Gustav Adolf, in 1778. The second part deals with the establishment of the Court of Appeal in Vasa in 1776. The formation of the Appeals Court was accompanied by a host of ceremonial, rhetorical, emblematic, and architectural features solidifying its importance as one of Gustav III s most symbolic administrative reform projects and hence portraying the king as an enlightened monarch par excellence. The third and final part of the thesis engages with war as a cultural phenomenon and focuses on the Russo-Swedish War of 1788-1790. In this study, the war against Russia is primarily seen as an arena for the king and other players to stage, create and re-create as well as articulate themselves through scenes and roles adhering to a particular cultural idiom. Its codes and symbolic forms, then, were communicated by means of theatre, literature, art, history, and classical mythology. The dissertation makes use of a host of sources: protocols, speeches, letters, diaries, newspapers, poetry, art, medals, architecture, inscriptions and registers. Traditional political source material and literary and art sources are studied as totalities, not as separate entities. Also it is argued that political and non-fictional sources cannot be understood properly without acknowledging the context of genre, literary conventions, and artistic modes. The study critically views the futile, but nonetheless almost habitual juxtaposition of the reality of images, ideas, and metaphors, and the reality of supposedly factual historical events. Significantly, the thesis presumes the symbolic dimension to be a constitutive element of reality, not its cooked up misrepresentation. This presumption is reflected in a discussion of the concept of role , which should not be anachronistically understood as roles in which the king cast himself at different times and in different situations. Neither Gustav III nor other European sovereigns of this period played the roles as rulers or majesties. Rather, they were monarchs both in their own eyes and in the eyes of their contemporaries as well as in all relations and contexts. Key words: Eighteenth-Century, Gustav III, Cultural History, Monarchs, Royal Graces, the Vasa Court of Appeal, the Russo-Swedish War 1788–1790.

Many-body effects in electrochemisorption : Part III. Beyond mean field and hartree-fock

Several channels provided by many-body couplings — both fermion-fermion and fermion-boson — for the evolution of the chemisorption system are discussed. This provides an opportunity of a systematic study of the effects of correlations reflected through the intricate pole structure of the absorbate Green functions. The results of Newns, Anda and others in the context of chemisorption are generalized.

Photo-induced double-strand DNA and site-specific protein cleavage activity of L-histidine (mu-oxo)diiron(III) complexes of heterocyclic bases

Three oxo-bridged diiron(III) complexes of L-histidine and heterocyclic bases [Fe-2(mu-O)(L-his)(2)(B)(2)](ClO4)(2) (1-3), where B is 2,2'-bipyridine (bpy),1,10-phenanthroline (phen), dipyrido[3,2-d:2',3'-f]quinoxaline (dpq), were prepared and characterized. The bpy complex 1 was structurally characterized by X-ray crystallography. The molecular structure showed a {Fe-2(mu-O)} core in which iron(III) in a FeN4O2 coordination is bound to tridentate monoanionic L-histidine and bidentate bpy ligands. The Fe center dot center dot center dot Fe distance is similar to 3.5 angstrom. The Fe-O-Fe unit is essentially linear, giving a bond angle of similar to 172 degrees. The complexes showed irreversible cyclic voltammetric cathodic response near -0.1 V vs. SCE in H2O-0.1 M KCl. The binuclear units displayed antiferromagnetic interaction between two high-spin (S = 5/2) iron(III) centers giving a -J value of -110 cm(-1). The complexes showed good DNA binding propensity giving a binding constant value of similar to 10(5) M-1. Isothermal titration calorimetric data indicated single binding mode to the DNA. The binding was found to be driven by negative free energy change and enthalpy. The dpq complex 3 showed oxidative double-strand DNA cleavage on exposure to UV-A and visible light. The phen complex 2 displayed single-strand photocleavage of DNA. The DNA double-strand breaks were rationalized from theoretical molecular docking calculations. Mechanistic investigations showed formation of hydroxyl radicals as the reactive species through photodecarboxylation of the L-histidine ligand. The complexes exhibited good binding propensity to bovine serum albumin (BSA) protein in Tris-HCl/NaCl buffer medium. The dpq complex 3 showed UV-A light-induced site-specific oxidative BSA cleavage forming fragments of similar to 45 kDa and similar to 20 kDa molecular weights via SOH pathway.

A Magnetic Susceptibility Study of Spin-state Transitions in Rare-earth TrioxocobaItates( III)

Rare-earth trioxocobaltates(lll), Ln[CoO,], with Ln = Pr, Nd, Tb, Dy. and Yb exhibit low-spin to high-spin transitions of cobalt characterised by a maximum in the Ax-l against temperature plots where Ax is the cobalt contribution to the magnetic susceptibility. The susceptibility behaviour is distinct from that of La[CoO,] which shows a plateau in the x-I-T curve accompanied by a structural transition. The temperature at which the AX- I-T curve shows a maximum increases with the decrease in the size of the rare-earth ion. The susceptibility behavior of solid solutions of La,,Nd,CoO, has been investigated to see how the behaviour characteristic of Nd[CoO,] changes to that of La[CoO,].