A molecular anchor for stabilizing triple-helical DNA.

Molecular modeling has been used to predict that 2,6-disubstituted amidoanthraquinones, and not the 1,4 series, should preferentially interact with and stabilize triple-stranded DNA structures over duplex DNA. This is due to marked differences in the nature of chromophore-base stacking and groove accessibility for the two series. A DNA foot-printing method that monitors the extent of protection from DNase I cleavage on triplex formation has been used to examine the effects of a number of synthetic isomer compounds in the 1,4 and 2,6 series. The experimental results are in accord with the predicted behavior and confirm that the 1,4 series bind preferentially to double- rather than triple-stranded DNA, whereas the isomeric 2,6 derivatives markedly favor binding to triplex DNA.

Crystal structure of an H-2Kb-ovalbumin peptide complex reveals the interplay of primary and secondary anchor positions in the major histocompatibility complex binding groove.

Sequence analysis of peptides naturally presented by major histocompatibility complex (MHC) class I molecules has revealed allele-specific motifs in which the peptide length and the residues observed at certain positions are restricted. Nevertheless, peptides containing the standard motif often fail to bind with high affinity or form physiologically stable complexes. Here we present the crystal structure of a well-characterized antigenic peptide from ovalbumin [OVA-8, ovalbumin-(257-264), SIINFEKL] in complex with the murine MHC class I H-2Kb molecule at 2.5-A resolution. Hydrophobic peptide residues Ile-P2 and Phe-P5 are packed closely together into binding pockets B and C, suggesting that the interplay of peptide anchor (P5) and secondary anchor (P2) residues can couple the preferred sequences at these positions. Comparison with the crystal structures of H-2Kb in complex with peptides VSV-8 (RGYVYQGL) and SEV-9 (FAPGNYPAL), where a Tyr residue is used as the C pocket anchor, reveals that the conserved water molecule that binds into the B pocket and mediates hydrogen bonding from the buried anchor hydroxyl group could not be likewise positioned if the P2 side chain were of significant size. Based on this structural evidence, H-2Kb has at least two submotifs: one with Tyr at P5 (or P6 for nonamer peptides) and a small residue at P2 (i.e., Ala or Gly) and another with Phe at P5 and a medium-sized hydrophobic residue at P2 (i.e., Ile). Deciphering of these secondary submotifs from both crystallographic and immunological studies of MHC peptide binding should increase the accuracy of T-cell epitope prediction.

Ethnic Violence on Kenya's Periphery: Informal Institutions and Local Resilience in Conflict-Affected Communities

Deadly, inter-ethnic group conflict remains a threat to international security in a world where the majority of armed violence occurs not only within states but in the most ungoverned areas within states. Conflicts that occur between groups living in largely ungoverned areas often become deeply protracted and are difficult to resolve when the state is weak and harsh environmental conditions place human security increasingly under threat. However, even under these conditions, why do some local conflicts between ethnic groups escalate, whereas others do not? To analyze this puzzle, the dissertation employs comparative methods to investigate the conditions under which violence erupts or stops and armed actors choose to preserve peace. The project draws upon qualitative data derived from semi-structured interviews, focus group dialogues, and participant observation of local peace processes during field research conducted in six conflict-affected counties in Northern Kenya. Comparative analysis of fifteen conflict episodes with variable outcomes reveals the conditions under which coalitions of civic associations, including local peace committees, faith-based organizations, and councils of elders, inter alia, enhance informal institutional arrangements that contain escalation. Violence is less likely to escalate in communities where cohesive coalitions provide platforms for threat-monitoring, informal pact making, and enforcement of traditional codes of restitution. However, key scope conditions affect whether or not informal organizational structures are capable of containing escalation. In particular, symbolic acts of violence and the use of indiscriminant force by police and military actors commonly undermine local efforts to contain conflict. The dissertation contributes to the literatures on civil society and peacebuilding, demonstrating the importance of comparing processes of escalation and non-escalation and accounting for interactive effects between modes of state and non-state response to local, inter-ethnic group conflict.

Influence of Religious Institutions in the Creation and Implementation of Public Policy: The Case of Roman Catholic Argentina and Secular Uruguay

The strong presence of religious institutions in Latin America, especially the Roman Catholic Church, and their participation in the creation and implementation of public policy within a sovereign state can be counter-productive for the social development and progress of that specific country. Argentina and Uruguay and the social controversy of social issues of abortion and same-sex marriage are used as examples to establish the accuracy of the above statement. Historical, statistical, and legislative information about both topics in both countries show that the political power that the Roman Catholic Church has in the region is more an outdated influence than a reality, and the principle of secularization appears to be the most stabilizing philosophy for modern nations.

Management of subluxated cataract with capsule anchor implantation

We describe a small case series that provides preliminary evidence of the usefulness of a new capsule-anchoring device for the management of subluxated cataracts. Three eyes of 3 patients with traumatic subluxated cataract causing a significant visual loss were enrolled. Phacoemulsification was performed in all cases with implantation of a capsule-anchoring device (AssiAnchor) because partial zonular dehiscence was present. A significant visual improvement was achieved in the 3 cases. The capsular bag was well centered and the anchors firmly attached to the capsulorhexis and sclera at 12 months postoperatively. The capsule-anchoring device was helpful in managing traumatic subluxated cataracts, enabling effective centration of the intraocular lens–capsular bag complex and, consequently, effective visual restoration.