325 research outputs found

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    A 'Whole-of-Society Approach' to Refugee Protection in Asia

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    This thesis challenges common assumptions in the literature about an Asian rejection of refugee rights. It argues that legal protection for refugees is available in both State Parties and Non-State Parties to the Refugee Convention and Protocol in Asia, even if the systems and practices vary. A review of legal frameworks and State practice demonstrates that every State reviewed recognizes certain legal obligations and standards of treatment towards refugees. Importantly, these include non-refoulement, temporary refuge, and respect for human and some refugee-specific rights. The thesis utilzes a historical and comparative methodology, emphasizing the impact of colonial legacies, the cold war, and modern power politics on Asian State perspectives and policies. It compares how refugee protection is actually managed in practice on the ground in 10 jurisdictions across Asia. This provides an evidence base with empirical material detailing the existing structures and systems of protection as they currently exist. A stakeholder analysis demonstrates that while States and UNHCR have legal obligations, effective refugee protection requires collaboration among a diverse set of stakeholders with the capacities required to meet the needs of refugee and host communities. On the basis of evidence provided, the thesis finds that there are legal standards, common typologies, and common characteristics among systems that can be used to inform the development of new structures and to support the evaluation and strenghtening of existing systems. The thesis concludes that the starting point for improved protection outcomes in Asia is not accession to the Refugee Convention. It is the more pragmatic work of developing local protection capacity among a diverse set of collaborating stakeholders across a ‘whole-of-society approach’

    Transferring cultures across imagined borders: a look at Quentin Compson and Martin Arrowsmith

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    The purpose of this thesis is to examine two of American modernism's more successful authors, and the unconventional pairing of two of their more recognized characters, in an attempt to provide a new regionalist argument for the rejection of socially created local values when those values are transferred across imagined regional lines. Chapter I presents the argument based on research in American regionalism, American modernism, and criticism of the mass market culture that developed at the turn of the twentieth-century. Chapter II examines William Faulkner's Quentin Compson and his role as a mobile narrative that moves from the South of Faulkner's Mississippi in The Sound and the Fury and Absalom, Absalom! to Cambridge, MA through close readings of both novels in conjunction with recent and traditional criticism of both Faulkner and Quentin. Chapter III examines Sinclair Lewis's Martin Arrowsmith and his role as a mobile narrative that represents a group of politicized American values, and the effects of his travels through different regions within the text of Arrowsmith. The result of this thesis will be to expose a critical approach to modern regionalism that has not been effectively used to its fullest potential in literary scholarship of the past

    HIV-1/HSV-2 Co-Infected Adults in Early HIV-1 Infection Have Elevated CD4+ T Cell Counts

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    Introduction. HIV-1 is often acquired in the presence of pre-existing co-infections, such as Herpes Simplex Virus 2 (HSV-2). We examined the impact of HSV-2 status at the time of HIV-1 acquisition for its impact on subsequent clinical course, and total CD4+ T cell phenotypes. Methods. We assessed the relationship of HSV-1/HSV-2 co-infection status on CD4+ T cell counts and HIV-1 RNA levels over time prior in a cohort of 186 treatment naive adults identified during early HIV-1 infection. We assessed the activation and differentiation state of total CD4+ T cells at study entry by HSV-2 status. Results. of 186 recently HIV-1 infected persons, 101 (54%) were sero-positive for HSV-2. There was no difference in initial CD8+ T cell count, or differences between the groups for age, gender, or race based on HSV-2 status. Persons with HIV-1/HSV-2 co-infection sustained higher CD4+ T cell counts over time (+69 cells/ul greater (SD = 33.7, p = 0.04) than those with HIV-1 infection alone (Figure 1), after adjustment for HIV-1 RNA levels (-57 cells per 1 log(10) higher HIV-1 RNA, p<0.0001). We did not observe a relationship between HSV-2 infection status with plasma HIV-1 RNA levels over time. HSV-2 acquistion after HIV-1 acquisition had no impact on CD4+ count or viral load. We did not detect differences in CD4+ T cell activation or differentiation state by HSV-2+ status. Discussion. We observed no effect of HSV-2 status on viral load. However, we did observe that treatment naive, recently HIV-1 infected adults co-infected with HSV-2+ at the time of HIV-1 acquisition had higher CD4+ T cell counts over time. If verified in other cohorts, this result poses a striking paradox, and its public health implications are not immediately clear.Brazilian Program for STD and AIDS, Ministry of HealthSão Paulo City Health DepartmentFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)NIAID/NIHJohn E. Fogarty International CenterAIDS Research Institute of the AIDS Biology Program at UCSFCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Brazilian Ministry of EducationUniversidade Federal de São Paulo, Div Infect Dis, São Paulo, BrazilUniv Calif San Francisco, San Francisco Gen Hosp, Div HIV AIDS, San Francisco, CA USAUniv Calif San Francisco, Dept Expt Med, San Francisco, CA USASao Paula City Hlth Syst, São Paulo, BrazilUniversidade Federal de São Paulo, Div Infect Dis, São Paulo, BrazilBrazilian Program for STD and AIDS, Ministry of Health: 914/BRA/3014 UNESCO/KallasSão Paulo City Health Department: 2004-0.168.922-7/KallasFAPESP: 04/15856-9/KallasNIAID/NIH: AI066917/BarbourNIAID/NIH: AI064520/NixonJohn E. Fogarty International Center: D43 TW00003Web of Scienc

    Benchmark Acetylene Binding Affinity and Separation through Induced Fit in a Flexible Hybrid Ultramicroporous Material

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    Structural changes at the active site of an enzyme induced by binding to a substrate molecule can result in enhanced activity in biological systems. Herein, we report that the new hybrid ultramicroporous material sql-SIFSIX-bpe-Zn exhibits an induced fit binding mechanism when exposed to acetylene, C₂H₂. The resulting phase change affords exceptionally strong C₂H₂ binding that in turn enables highly selective C₂H₂/C₂H₄ and C₂H₂/CO₂ separation demonstrated by dynamic breakthrough experiments. sql-SIFSIX-bpe-Zn was observed to exhibit at least four phases: as-synthesised (α); activated (β); and C₂H₂ induced phases (β' and γ). sql-SIFSIX-bpe-Zn-β exhibited strong affinity for C₂H₂ at ambient conditions as demonstrated by benchmark isosteric heat of adsorption (Qst ) of 67.5 kJ mol⁻¹ validated through in situ pressure gradient differential scanning calorimetry (PG-DSC). Further, in situ characterisation and DFT calculations provide insight into the mechanism of the C₂H₂ induced fit transformation, binding positions and the nature of host-guest and guest-guest interactions

    The Lantern Vol. 62, No. 2, Summer 1995

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    • In the Season of Grief • Subtleties • Crazehaze • Blacksmith • I Feel Your Weight • L\u27Amour Manque • Sense of You • Greed • Gender (Rolled) • Soliloquy of a Punter • Nightmares • God is a Frisbee • Cleansing • Flat • Chemistry of Mind • Louderback • Ritual • Rebuilding Mother • Scott Lomba • The Acting Bug • Untitled • The Seek • Gluttony • Great South Bay • Archangel • Suburban Zeus • Vespers • At Change of A-Dress • The Hierarchy of Coolness • The Apology • I Know it is Evening There • Pridehttps://digitalcommons.ursinus.edu/lantern/1146/thumbnail.jp

    Ubiquitin ligase RNF8 suppresses Notch signaling to regulate mammary development and tumorigenesis

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    The E3 ubiquitin ligase RNF8 plays critical roles in maintaining genomic stability by promoting the repair of DNA double-strand breaks (DSBs) through ubiquitin signaling. Abnormal activation of Notch signaling and defective repair of DSBs promote breast cancer risk. Here, we found that low expression of the full-length RNF8 correlated with poor prognosis for breast cancer patients. Our data revealed that in addition to its role in the repair of DSBs, RNF8 regulated Notch1 signaling and cell-fate determination of mammary luminal progenitors. Mechanistically, RNF8 acted as a negative regulator of Notch signaling by ubiquitylating the active NOTCH1 protein (N1ICD), leading to its degradation. Consistent with abnormal activation of Notch signaling and impaired repair of DSBs in Rnf8-mutant mammary epithelial cells, we observed increased risk of mammary tumorigenesis in mouse models for RNF8 deficiency. Notably, deficiency of RNF8 sensitized breast cancer cells to combination of pharmacological inhibitors of Notch signaling and poly(AOP-ribose) polymerase (PARP), suggesting implications for treatment of breast cancer associated with impaired RNF8 expression or function

    Randomized, Controlled Trial of Therapy Interruption in Chronic HIV-1 Infection

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    BACKGROUND: Approaches to limiting exposure to antiretroviral therapy (ART) drugs are an active area of HIV therapy research. Here we present longitudinal follow-up of a randomized, open-label, single-center study of the immune, viral, and safety outcomes of structured therapy interruptions (TIs) in patients with chronically suppressed HIV-1 infection as compared to equal follow-up of patients on continuous therapy and including a final therapy interruption in both arms. METHODS AND FINDINGS: Forty-two chronically HIV-infected patients on suppressive ART with CD4 counts higher than 400 were randomized 1:1 to either (1) three successive fixed TIs of 2, 4, and 6 wk, with intervening resumption of therapy with resuppression for 4 wk before subsequent interruption, or (2) 40 wk of continuous therapy, with a final open-ended TI in both treatment groups. Main outcome was analysis of the time to viral rebound (>5,000 copies/ml) during the open-ended TI. Secondary outcomes included study-defined safety criteria, viral resistance, therapy failure, and retention of immune reconstitution. There was no difference between the groups in time to viral rebound during the open-ended TI (continuous therapy/single TI, median [interquartile range] = 4 [1–8] wk, n = 21; repeated TI, median [interquartile range] = 5 [4–8] wk, n = 21; p = 0.36). No differences in study-related adverse events, viral set point at 12 or 20 wk of open-ended interruption, viral resistance or therapy failure, retention of CD4 T cell numbers on ART, or retention of lymphoproliferative recall antigen responses were noted between groups. Importantly, resistance detected shortly after initial viremia following the open-ended TI did not result in a lack of resuppression to less than 50 copies/ml after reinitiation of the same drug regimen. CONCLUSION: Cycles of 2- to 6-wk time-fixed TIs in patients with suppressed HIV infection failed to confer a clinically significant benefit with regard to viral suppression off ART. Also, secondary analysis showed no difference between the two strategies in terms of safety, retention of immune reconstitution, and clinical therapy failure. Based on these findings, we suggest that further clinical research on the long-term consequences of TI strategies to decrease drug exposure is warranted
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