Re-imagining DDR Ex-combatants, leadership and moral agency in conflict transformation

Drawing upon criminological studies in the field of prisoner rehabilitation, this essay explores the relevance of the Demobilisation, Disarmament and Reintegration (DDR) framework to the process of conflict transformation in Northern Ireland. In a similar fashion to the critique of 'passivity' offered by, for example, the 'strengths based' or 'good lives' approach to prisoner resettlement and reintegration more generally, the authors contend that the Northern Ireland peace process offers conspicuous examples of former prisoners and combatants as agents and indeed leaders in the process of conflict transformation. They draw out three broad styles of leadership which have emerged amongst ex-combatants over the course of the Northern Ireland transition from conflict-political, military and communal. They suggest that cumulatively such leadership speaks to the potential of ex-prisoners and ex-combatants as moral agents in conflict transformation around which peacemaking can be constructed rather than as obstacles which must be 'managed' out of existence.

Expanding DDR: The Transformative Role of Former Prisoners in Community-Based Reintegration in Northern Ireland

This article explores the process of Disarmament, Demobilization and Reintegration (DDR) in Northern Ireland. In particular, it examines the role and experiences of former combatants, who were incarcerated during the Troubles. It is shown that upon release from prison, many of these former combatants have played key roles in the development of community-based initiatives, which have not only facilitated the reintegration of former prisoners, but have also contributed to a broader process of post-conflict regeneration and social development. The author considers the notion of expanding the ‘R’ phase of DDR, and contends that additional attention needs to be paid to both to the specific needs of former combatants/former prisoners and to their involvement in the overall process of reintegration and peacebuilding.

High performance IP lookup circuit using DDR SDRAM

DDR-SDRAM based data lookup techniques are evolving into a core technology for packet lookup applications for data network, benefitting from the features of high density, high bandwidth and low price of DDR memory products in the market. Our proposed DDR-SDRAM based lookup circuit is capable of achieving IP header lookup for network line-rates of up to 10Gbps, providing a solution on high-performance and economic packet header inspections. ©2008 IEEE.

The Liedertheater of Wenzel and Mensching: Subversive Use of the Agitprop and Clowning Tradition in the GDR

The East German poet-clowns Hans-Eckardt Wenzel and Steffen Mensching rose to prominence during the GDR's (German Democratic Republic; Deutsche Demokratische Republik, DDR) Peaceful Revolution of autumn 1989 with their cabaret production Letztes aus der Da Da eR. A film adaptation of the production was made by Jörg Foth in 1990, which was finally released on DVD with English subtitles in the United Kingdom and North America in 2009 (Latest from the Da-Da-R). In light of this long-overdue interest in Wenzel & Mensching, this article will attempt to put the work of the duo in historical and aesthetic context. Their use of character, masks, music, and philosophy combined to create the distinctly grotesque world that constituted their Liedertheater performances.

Valved Dataflow For FPGA Memory Hierarchy Synthesis

For modern FPGA, implementation of memory intensive processing applications such as high end image and video processing systems necessitates manual design of complex multilevel memory hierarchies incorporating off-chip DDR and onchip BRAM and LUT RAM. In fact, automated synthesis of multi-level memory hierarchies is an open problem facing high level synthesis technologies for FPGA devices. In this paper we describe the first automated solution to this problem.
By exploiting a novel dataflow application modelling dialect, known as Valved Dataflow, we show for the first time how, not only can such architectures be automatically derived, but also that the resulting implementations support real-time processing for current image processing application standards such as H.264. We demonstrate the viability of this approach by reporting the performance and cost of hierarchies automatically generated for Motion Estimation, Matrix Multiplication and Sobel Edge Detection applications on Virtex-5 FPGA.

A theoretical examination of known and hypothetical clathrate hydrate materials

The recent synthesis of a new hydrogen binary hydrate with the sH structure has highlighted the potential storage capabilities of water clathrates [T. A. Strobel, C. A. Koh, and E. D. Sloan, J. Phys. Chem. B 112, 1885 (2008) and A. R. C. Duarte, A. Shariati, L. J. Rovetto, and C. J. Peters, J. Phys. Chem. B 112, 1888 (2008)]. In this work, the absorption of hydrogen and the promoters used in the experimental work are considered using a simplified model for the host-guest interaction, which allows one to understand the stabilizing effects of multiple help molecules. Two further hypothetical clathrates, which are isostructural with known zeolite structures, are also investigated. It is shown that the energy gained by absorbing adamantane into these two frameworks is far greater than that gained upon absorption of adamantane into the sH structure. Hence, a clathrate with the same topology as the DDR (Sigma 1) zeolite may be synthesizable with adamantane and hydrogen as guest molecules as, in the conditions explored here, this phase appears to be more stable than the sH structure. (C) 2009 American Institute of Physics. [DOI: 10.1063/1.3142503]

Identification and Validation of an Anthracycline/Cyclophosphamide–Based Chemotherapy Response Assay in Breast Cancer

Background: There is no method routinely used to predict response to anthracycline and cyclophosphamide–based chemotherapy in the clinic; therefore patients often receive treatment for breast cancer with no benefit. Loss of the Fanconi anemia/BRCA (FA/BRCA) DNA damage response (DDR) pathway occurs in approximately 25% of breast cancer patients through several mechanisms and results in sensitization to DNA-damaging agents. The aim of this study was to develop an assay to detect DDR-deficient tumors associated with loss of the FA/BRCA pathway, for the purpose of treatment selection.

Methods: DNA microarray data from 21 FA patients and 11 control subjects were analyzed to identify genetic processes associated with a deficiency in DDR. Unsupervised hierarchical clustering was then performed using 60 BRCA1/2 mutant and 47 sporadic tumor samples, and a molecular subgroup was identified that was defined by the molecular processes represented within FA patients. A 44-gene microarray-based assay (the DDR deficiency assay) was developed to prospectively identify this subgroup from formalin-fixed, paraffin-embedded samples. All statistical tests were two-sided.

Results: In a publicly available independent cohort of 203 patients, the assay predicted complete pathologic response vs residual disease after neoadjuvant DNA-damaging chemotherapy (5-fluorouracil, anthracycline, and cyclophosphamide) with an odds ratio of 3.96 (95% confidence interval [Cl] =1.67 to 9.41; P = .002). In a new independent cohort of 191 breast cancer patients treated with adjuvant 5-fluorouracil, epirubicin, and cyclophosphamide, a positive assay result predicted 5-year relapse-free survival with a hazard ratio of 0.37 (95% Cl = 0.15 to 0.88; P = .03) compared with the assay negative population.

Conclusions: A formalin-fixed, paraffin-embedded tissue-based assay has been developed and independently validated as a predictor of response and prognosis after anthracycline/cyclophosphamide–based chemotherapy in the neoadjuvant and adjuvant settings. These findings warrant further validation in a prospective clinical study.

Financial reintegration assistance for veterans of the Irish revolution (1916-23): post-conflict policy in an historical setting

In the aftermath of the Irish revolution and Civil War the governments of independent Ireland introduced various compensation schemes to provide financial reintegration assistance to revolutionary veterans. This would be recognised today as part of a programme for DDR. This paper will examine various service and disability pensions paid to veterans in the context of literature on post-conflict reintegration. It will examine various challenges to reintegration in an effort to analyse the success of revolutionary compensation as a post-conflict reintegration mechanism in independent Ireland after 1922.

Mechanistic Rationale to Target PTEN-Deficient Tumor Cells with Inhibitors of the DNA Damage Response Kinase ATM

Ataxia telangiectasia mutated (ATM) is an important signaling molecule in the DNA damage response (DDR). ATM loss of function can produce a synthetic lethal phenotype in combination with tumor-associated mutations in FA/BRCA pathway components. In this study, we took an siRNA screening strategy to identify other tumor suppressors that, when inhibited, similarly sensitized cells to ATM inhibition. In this manner, we determined that PTEN and ATM were synthetically lethal when jointly inhibited. PTEN-deficient cells exhibited elevated levels of reactive oxygen species, increased endogenous DNA damage, and constitutive ATM activation. ATM inhibition caused catastrophic DNA damage, mitotic cell cycle arrest, and apoptosis specifically in PTEN-deficient cells in comparison with wild-type cells. Antioxidants abrogated the increase in DNA damage and ATM activation in PTEN-deficient cells, suggesting a requirement for oxidative DNA damage in the mechanism of cell death. Lastly, the ATM inhibitor KU-60019 was specifically toxic to PTEN mutant cancer cells in tumor xenografts and reversible by reintroduction of wild-type PTEN. Together, our results offer a mechanistic rationale for clinical evaluation of ATM inhibitors in PTEN-deficient tumors.

The Nuclear Oncogene SET Controls DNA Repair by KAP1 and HP1 Retention to Chromatin

Cells experience damage from exogenous and endogenous sources that endanger genome stability. Several cellular pathways have evolved to detect DNA damage and mediate its repair. Although many proteins have been implicated in these processes, only recent studies have revealed how they operate in the context of high-ordered chromatin structure. Here, we identify the nuclear oncogene SET (I2PP2A) as a modulator of DNA damage response (DDR) and repair in chromatin surrounding double-strand breaks (DSBs). We demonstrate that depletion of SET increases DDR and survival in the presence of radiomimetic drugs, while overexpression of SET impairs DDR and homologous recombination (HR)-mediated DNA repair. SET interacts with the Kruppel-associated box (KRAB)-associated co-repressor KAP1, and its overexpression results in the sustained retention of KAP1 and Heterochromatin protein 1 (HP1) on chromatin. Our results are consistent with a model in which SET-mediated chromatin compaction triggers an inhibition of DNA end resection and HR.

Per-Flow State Management Technique for High-Speed Networks

Flow processing is a fundamental element of stateful traffic classification and it has been recognized as an essential factor for delivering today’s application-aware network operations and security services. The basic function within a flow processing engine is to search and maintain a flow table, create new flow entries if no entry matches and associate each entry with flow states and actions for future queries. Network state information on a per-flow basis must be managed in an efficient way to enable Ethernet frame transmissions at 40 Gbit/s (Gbps) and 100 Gbps in the near future. This paper presents a hardware solution of flow state management for implementing large-scale flow tables on popular computer memories using DDR3 SDRAMs. Working with a dedicated flow lookup table at over 90 million lookups per second, the proposed system is able to manage 512-bit state information at run time.

AURKA overexpression accompanies dysregulation of DNA-damage response genes in invasive urothelial cell carcinoma

Invasive urothelial cell carcinoma (UCC) is characterized by increased chromosomal instability and follows an aggressive clinical course in contrast to non-invasive disease. To identify molecular processes that confer and maintain an aggressive malignant phenotype, we used a high-throughput genome-wide approach to interrogate a cohort of high and low clinical risk UCC tumors. Differential expression analyses highlighted cohesive dysregulation of critical genes involved in the G(2)/M checkpoint in aggressive UCC. Hierarchical clustering based on DNA Damage Response (DDR) genes separated tumors according to a pre-defined clinical risk phenotype. Using array-comparative genomic hybridization, we confirmed that the DDR was disrupted in tumors displaying high genomic instability. We identified DNA copy number gains at 20q13.2-q13.3 (AURKA locus) and determined that overexpression of AURKA accompanied dysregulation of DDR genes in high risk tumors. We postulated that DDR-deficient UCC tumors are advantaged by a selective pressure for AURKA associated override of M phase barriers and confirmed this in an independent tissue microarray series. This mechanism that enables cancer cells to maintain an aggressive phenotype forms a rationale for targeting AURKA as a therapeutic strategy in advanced stage UCC.