An Investment Case for Addressing Social Drivers of Structural Stigma and Discrimination Against Refugees in Resource-Poor Urban Areas

Investment in addressing structural stigma and discrimination against refugees in resource-poor urban areas is both needed, and possible. The large population of refugees residing in resource-poor urban areas is likely to grow, and tensions in a number of settings are now documented. Without interventions to adequately address such tensions, both the protection needs of refugee populations and the stability of hosting countries could be affected. Through qualitative analysis of an urban refugee dataset in Uganda, this dissertation identified community-level drivers of structural stigma and discrimination as safeguarding one’s body and property, defending status, and perpetuating exploitation. The designs of potentially successful programs to address these drivers were then identified though systematic review, and included one or more of the following: 1) the utilization of multiple intervention components; 2) direct information provision (e.g., lecture, role-play, other active engagement) or direct contact with stigmatized groups; 3) cooperative work between community members and stigmatized groups to better livelihoods; 4) popular opinion leaders who have authority to make change, and 5) traditional ceremonies valued by the communities for cleansing and healing. One such design involving an agricultural livelihood program in a resource-poor urban area of the Northeast United States was costed, utilizing a primarily bottom-up approach and a societal perspective in the collection of both financial and economic costs. The unit cost per participating family was significantly lower than government services that provide comparable nutritional support, but did not include components of working with the community to reduce stigma and discrimination. Thus, the studied program provided more services for a lower cost. In addition, it empowered stigmatized refugees to advocate for and support themselves, and engendered goodwill in the community by involving community members to work alongside refugee participants, improving upon a neglected piece of land, and providing fresh produce. Further research is needed to better measure the social and financial dividends of programs to address structural stigma and discrimination, particularly against urban refugees. Such research can only come in tandem with further investment, the imperative and potential of which are compellingly clear

Geometry of s-space and its using for modeling and optimization complex systems

Описано компоненти хвильової моделі С-простору - аксіоми, теореми самоорганізації, діаграми. Розглянуто загальну модель “людина - навколишнє середовище” й деякі з робочих моделей, приклади застосування теорії самоорганізації С-простору при оптимізації складних технологічних системОписаны компоненты волновой модели С-пространства - аксиомы, теоремы самоорганизации, диаграммы. Рассмотрены общая модель «человек - окружающая среда» и некоторые из рабочих моделей, примеры применения теории самоорганизации С-пространства при оптимизации сложных технологических системComponents of the S-space wave model - axioms, self-organization theory, mappings - are described.The general model “human-environment” and some of the working models are considered. Also contains examples of application of the S-space self-organization theory by optimization of complex technological system

The fall and rise of Pennsylvania Station : changing attitudes toward historic preservation in New York City

Thesis (M.C.P.)--Massachusetts Institute of Technology, Dept. of Urban Studies and Planning, February 2000."February 2000." Vita.Includes bibliographical references (p. 73-79).In 1910, the Pennsylvania Railroad constructed Pennsylvania Station, its New York City terminal. Built and designed as a "monumental gateway," an important civic structure as well as a transportation hub, the station became an important part of New York's urban fabric. Its success inspired the United States government to construct the adjacent Farley Post Office as an architectural and functional complement to Penn Station. By 1963, changing economic conditions and the evolving nature of passenger transportation prompted the Pennsylvania Railroad to announce plans to sell development rights on the Penn Station site. The station would be demolished and replaced with a new Madison Square Garden complex; the railroad would create a new underground "Penn Station" beneath the Garden. These plans prompted tremendous public and editorial outcry on a scale never before seen, thus beginning the historic-preservation movement in New York City. Although in 1963 the city had no authority to intervene, and Penn Station was indeed demolished as planned, Mayor Robert Wagner in 1965 signed New York City's Landmarks Law, establishing the Landmarks Preservation Commission. The Commission had the power to protect designated landmarks from demolition. By the 1990s, the city's attitude toward historic preservation had come full circle, as vividly illustrated by new plans to renovate a portion of the Farley Post Office as a new Penn Station waiting area and concourse. This thesis uses the example of Penn Station's fall and rise to chronicle and analyze New York's change in attitude toward historic preservation.by Eric J. Plosky.M.C.P

ATR-mediated phosphorylation of DNA polymerase η is needed for efficient recovery from UV damage

DNA polymerase η (polη) belongs to the Y-family of DNA polymerases and facilitates translesion synthesis past UV damage. We show that, after UV irradiation, polη becomes phosphorylated at Ser601 by the ataxia-telangiectasia mutated and Rad3-related (ATR) kinase. DNA damage–induced phosphorylation of polη depends on its physical interaction with Rad18 but is independent of PCNA monoubiquitination. It requires the ubiquitin-binding domain of polη but not its PCNA-interacting motif. ATR-dependent phosphorylation of polη is necessary to restore normal survival and postreplication repair after ultraviolet irradiation in xeroderma pigmentosum variant fibroblasts, and is involved in the checkpoint response to UV damage. Taken together, our results provide evidence for a link between DNA damage–induced checkpoint activation and translesion synthesis in mammalian cells

Regulation of proliferating cell nuclear antigen ubiquitination in mammalian cells

After exposure to DNA-damaging agents that block the progress of the replication fork, monoubiquitination of proliferating cell nuclear antigen (PCNA) mediates the switch from replicative to translesion synthesis DNA polymerases. We show that in human cells, PCNA is monoubiquitinated in response to methyl methanesulfonate and mitomycin C, as well as UV light, albeit with different kinetics, but not in response to bleomycin or camptothecin. Cyclobutane pyrimidine dimers are responsible for most of the PCNA ubiquitination events after UV-irradiation. Failure to ubiquitinate PCNA results in substantial sensitivity to UV and methyl methanesulfonate, but not to camptothecin or bleomycin. PCNA ubiquitination depends on Replication Protein A (RPA), but is independent of ATR-mediated checkpoint activation. After UV-irradiation, there is a temporal correlation between the disappearance of the deubiquitinating enzyme USP1 and the presence of PCNA ubiquitination, but this correlation was not found after chemical mutagen treatment. By using cells expressing photolyases, we are able to remove the UV lesions, and we show that PCNA ubiquitination persists for many hours after the damage has been removed. We present a model of translesion synthesis behind the replication fork to explain the persistence of ubiquitinated PCNA

The business case for investing in social and behavior change for family planning

Although the development field generally considers social and behavior change interventions essential parts of quality health programs, lack of synthesized information on costs and effectiveness means that decision-makers under-appreciate and under-fund social and behavior change efforts. This business case uses evidence to answer questions about the effectiveness, cost, cost-effectiveness, and return on investment from social and behavior change efforts. To develop this family planning social and behavior change business case, nearly 200 studies were evaluated. All USAID strategic priorities for global health—preventing child and maternal deaths, controlling the HIV/AIDS epidemic, and combating infectious diseases—employ social and behavior change approaches to varying degrees. This is the first in a planned series of complementary, health area-specific business cases

129-derived Strains of Mice Are Deficient in DNA Polymerase ι and Have Normal Immunoglobulin Hypermutation

Recent studies suggest that DNA polymerase η (polη) and DNA polymerase ι (polι) are involved in somatic hypermutation of immunoglobulin variable genes. To test the role of polι in generating mutations in an animal model, we first characterized the biochemical properties of murine polι. Like its human counterpart, murine polι is extremely error-prone when catalyzing synthesis on a variety of DNA templates in vitro. Interestingly, when filling in a 1 base-pair gap, DNA synthesis and subsequent strand displacement was greatest in the presence of both pols ι and η. Genomic sequence analysis of Poli led to the serendipitous discovery that 129-derived strains of mice have a nonsense codon mutation in exon 2 that abrogates production of polι. Analysis of hypermutation in variable genes from 129/SvJ (Poli−/−) and C57BL/6J (Poli+/+) mice revealed that the overall frequency and spectrum of mutation were normal in polι-deficient mice. Thus, either polι does not participate in hypermutation, or its role is nonessential and can be readily assumed by another low-fidelity polymerase

Regulation of Translesion Synthesis DNA Polymerase η by Monoubiquitination

DNA polymerase eta is a Y family polymerase involved in translesion synthesis (TLS). Its action is initiated by simultaneous interaction between the PIP box in pol eta and PCNA and between the UBZ in pol eta and monoubiquitin attached to PCNA. Whereas monoubiquitination of PCNA is required for its interaction with pol eta during TLS, we now show that monoubiquitination of pol eta inhibits this interaction, preventing its functions in undamaged cells. Identification of monoubiquitination sites within pol eta nuclear localization signal (NLS) led to the discovery that pol eta NLS directly contacts PCNA, forming an extended pol eta-PCNA interaction surface. We name this the PCNA-interacting region (PIR) and show that its monoubiquitination is downregulated by various DNA-damaging agents. We propose that this mechanism ensures optimal availability of nonubiquitinated, TLS-competent pol eta after DNA damage. Our work shows how monoubiquitination can either positively or negatively regulate the assembly of a protein complex, depending on which substrates are targeted by ubiquitin

Addressing Inequity to Achieve the Maternal and Child Health Millennium Development Goals: Looking Beyond Averages.

Inequity in access to and use of child and maternal health interventions is impeding progress towards the maternal and child health Millennium Development Goals. This study explores the potential health gains and equity impact if a set of priority interventions for mothers and under fives were scaled up to reach national universal coverage targets for MDGs in Tanzania. We used the Lives Saved Tool (LiST) to estimate potential reductions in maternal and child mortality and the number of lives saved across wealth quintiles and between rural and urban settings. High impact maternal and child health interventions were modelled for a five-year scale up, by linking intervention coverage, effectiveness and cause of mortality using data from Tanzania. Concentration curves were drawn and the concentration index estimated to measure the equity impact of the scale up. In the poorest population quintiles in Tanzania, the lives of more than twice as many mothers and under-fives were likely to be saved, compared to the richest quintile. Scaling up coverage to equal levels across quintiles would reduce inequality in maternal and child mortality from a pro rich concentration index of -0.11 (maternal) and -0.12 (children) to a more equitable concentration index of -0,03 and -0.03 respectively. In rural areas, there would likely be an eight times greater reduction in maternal deaths than in urban areas and a five times greater reduction in child deaths than in urban areas. Scaling up priority maternal and child health interventions to equal levels would potentially save far more lives in the poorest populations, and would accelerate equitable progress towards maternal and child health MDGs