• R-Roscovitine (Seliciclib) prevents DNA damage-induced cyclin A1 upregulation and hinders non-homologous end-joining (NHEJ) DNA repair

      Federico, M; Symonds, CE; Bagella, L; Rizzolio, F; Fanale, D; Russo, A; Giordano, A; Giordano, Antonio|0000-0002-5959-016X (2010-08-04)
      Background: CDK-inhibitors can diminish transcriptional levels of cell cycle-related cyclins through the inhibition of E2F family members and CDK7 and 9. Cyclin A1, an E2F-independent cyclin, is strongly upregulated under genotoxic conditions and functionally was shown to increase NHEJ activity. Cyclin A1 outcompetes with cyclin A2 for CDK2 binding, possibly redirecting its activity towards DNA repair. To see if we could therapeutically block this switch, we analyzed the effects of the CDK-inhibitor R-Roscovitine on the expression levels of cyclin A1 under genotoxic stress and observed subsequent DNA damage and repair mechanisms.Results: We found that R-Roscovitine alone was unable to alter cyclin A1 transcriptional levels, however it was able to reduce protein expression through a proteosome-dependent mechanism. When combined with DNA damaging agents, R-Roscovitine was able to prevent the DNA damage-induced upregulation of cyclin A1 on a transcriptional and post-transcriptional level. This, moreover resulted in a significant decrease in non-homologous end-joining (NHEJ) paired with an increase in DNA DSBs and overall DNA damage over time. Furthermore, microarray analysis demonstrated that R-Roscovitine affected DNA repair mechanisms in a more global fashion.Conclusions: Our data reveal a new mechanism of action for R-Roscovitine on DNA repair through the inhibition of the molecular switch between cyclin A family members under genotoxic conditions resulting in reduced NHEJ capability. © 2010 Federico et al; licensee BioMed Central Ltd.
    • Racial differences in the responses to shear stress in human umbilical vein endothelial cells

      Feairheller, DL; Park, JY; Rizzo, V; Kim, B; Brown, MD (2011-01-01)
      Background: African American ethnicity is an independent risk factor for exaggerated oxidative stress, which is related to inflammation, hypertension, and cardiovascular disease. Recently, we reported that in vitro oxidative stress and inflammation levels differ between African American and Caucasian human umbilical vein endothelial cells (HUVECs), African American HUVECs having higher levels of both. However, it remains to be shown whether the cells would respond differently to external stimuli. Methods: We used a cone and plate viscometer to apply laminar shear stress (LSS) as an aerobic exercise mimetic to compare the responses by race. HUVECs were exposed to static conditions (no LSS), low LSS (5 dyne/cm2), and moderate LSS (20 dyne/cm2). Results: It was found that African American HUVECs had higher levels of oxidative stress under static conditions, and when LSS was applied protein expression levels (NADPH oxidase NOX2, NOX4 and p47phox subunits, eNOS, SOD2, and catalase) and biomarkers (NO, SOD, and total antioxidant capacity) were modulated to similar levels between race. Conclusion: African American HUVECs may be more responsive to LSS stimulus indicating that aerobic exercise prescriptions may be valuable for this population since the potential exists for large in vivo improvements in oxidative stress levels along the endothelial layer in response to increased shear flow. © 2011 Feairheller et al, publisher and licensee Dove Medical Press Ltd.
    • Racial differences in tumor necrosis factor-α-induced endothelial microparticles and interleukin-6 production

      Brown, MD; Feairheller, DL; Thakkar, S; Veerabhadrappa, P; Park, JY (2011-01-01)
      African Americans (AA) tend to have heightened systemic inflammation and endothelial dysfunction. Endothelial microparticles (EMP) are released from activated/apoptotic endothelial cells (EC) when stimulated by inflammation. The purpose of our study was to assess EMP responses to inflammatory cytokine (TNF-α) and antioxidant (superoxide dismutase, SOD) conditions in human umbilical vein ECs (HUVECs) obtained from AA and Caucasians. EMPs were measured under four conditions: control (basal), TNF-α, SOD, and TNF-α + SOD. Culture supernatant was collected for EMP analysis by flow cytometry and IL-6 assay by ELISA. IL-6 protein expression was assessed by Western blot. AA HUVECs had greater EMP levels under the TNF-α condition compared to the Caucasian HUVECs (6.8 ± 1.1 vs 4.7% ± 0.4%, P = 0.04). The EMP level increased by 89% from basal levels in the AA HUVECs under the TNF-α condition (P = 0.01) compared to an 8% increase in the Caucasian HUVECs (P = 0.70). Compared to the EMP level under the TNF-α condition, the EMP level in the AA HUVECs was lower under the SOD only condition (2.9% ± 0.3%, P = 0.005) and under the TNF-α + SOD condition (2.1% ± 0.4%, P = 0.001). Basal IL-6 concentrations were 56.1 ± 8.8 pg/mL/μg in the AA and 30.9 ± 14.9 pg/mL/μg in the Caucasian HUVECs (P = 0.17), while basal IL-6 protein expression was significantly greater (P < 0.05) in the AA HUVECs. These preliminary observational results suggest that AA HUVECs may be more susceptible to the injurious effects of the proinflammatory cytokine, TNF-α. © 2011 Brown et al, publisher and licensee Dove Medical Press Ltd.
    • Racial/ethnic differences in health insurance adequacy and consistency among children: Evidence from the 2011/12 National Survey of Children’s Health

      Soylu, TG; Elashkar, E; Aloudah, F; Ahmed, M; Kitsantas, P; Soylu, Tulay G.|0000-0003-2620-766X (2018-02-05)
      © T.G. Soylu et al., 2018. As the number of minority US children increases, monitoring racial/ethnic differences in health insurance coverage becomes critical in creating insurance programs that can provide adequate and consistent coverage. Using a nationally representative sample, the findings of this study suggest that low income and poor maternal health can adversely affect insurance consistency and adequacy for both minority and white children. This indicates that research studies on inequalities of healthcare coverage should also focus on underserved white populations of children as their insurance coverage is affected by similar factors as those for minority children. Elimination of inequalities may require targeted interventions that include the well-being of the entire family, cross-cultural education of healthcare providers, policy changes to grant low-income children with appropriate and reliable health insurance, and an ongoing monitoring of disparities by health plans.
    • Radiotherapy prolongs the survival of advanced non-smallcell lung cancer patients undergone to an immune-modulating treatment with dose-fractioned cisplatin and metronomic etoposide and bevacizumab (mPEBev)

      Pastina, P; Nardone, V; Botta, C; Croci, S; Tini, P; Battaglia, G; Ricci, V; Cusi, MG; Gandolfo, C; Misso, G; Zappavigna, S; Caraglia, M; Giordano, A; Aldinucci, D; Tassone, P; Tagliaferri, P; Pirtoli, L; Correale, P; Giordano, Antonio|0000-0002-5959-016X (2017-01-01)
      © Pastina et al. Radiotherapy (RT), together with a direct cytolytic effect on tumor tissue, also elicits systemic immunological events, which sometimes result in the regression of distant metastases (abscopal effect). We have shown the safety and anti-tumor activity of a novel metronomic chemotherapy (mCH) regimen with dose-fractioned cisplatin, oral etoposide and bevacizumab, a mAb against the vasculo-endothelial-growthfactor (mPEBev regimen), in metastatic non-small-cell-lung cancer (mNSCLC). This regimen, designed on the results of translational studies, showed immune-modulating effects that could trigger and empower the immunological effects associated with tumor irradiation. In order to assess this, we carried out a retrospective analysis in a subset of 69 consecutive patients who received the mPEBev regimen within the BEVA2007 trial. Forty-five of these patients, also received palliative RT of one or more metastatic sites. Statistical analysis (a Log-rank test) revealed a much longer median survival in the group of patients who received RT [mCH vs mCH + RT: 12.1 +/-2.5 (95%CI 3.35-8.6) vs 22.12 +/-4.3 (95%CI 11.9-26.087) months; P=0.015] with no difference in progression-free survival. In particular, their survival correlated with the mPEBev regimen ability to induce the percentage of activated dendritic cells (DCs) (CD3-CD11b+CD15-CD83+CD80+) [Fold to baseline value (FBV) ≤1 vs > 1: 4+/-5.389 (95%CI,0-14.56) vs 56+/-23.05 (95%CI,10.8-101.2) months; P:0.049)] and central-memory-T-cells (CD3+CD8+CD45RA-CCR7+) [FBV ≤1 vs > 1: 8+/-5.96 (95%CI,0-19.68) vs 31+/-12.3 (95%CI,6.94-55.1) months; P:0.045].
    • Randomised trial to evaluate the effectiveness and impact of offering postvisit decision support and assistance in obtaining physician-recommended colorectal cancer screening: The e-assist: Colon Health study - A protocol study

      Lafata, JE; Shin, Y; Flocke, SA; Hawley, ST; Jones, RM; Resnicow, K; Schreiber, M; Shires, DA; Tu, SP; Jones, Resa Marie|0000-0002-0080-4047 (2019-01-01)
      © © Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. Introduction How to provide practice-integrated decision support to patients remains a challenge. We are testing the effectiveness of a practice-integrated programme targeting patients with a physician recommendation for colorectal cancer (CRC) screening. Methods and analysis In partnership with healthcare teams, we developed 'e-assist: Colon Health', a patient-targeted, postvisit CRC screening decision support programme. The programme is housed within an electronic health record (EHR)-embedded patient portal. It leverages a physician screening recommendation as the cue to action and uses the portal to enrol and intervene with patients. Programme content complements patient-physician discussions by encouraging screening, addressing common questions and assisting with barrier removal. For evaluation, we are using a randomised trial in which patients are randomised to receive e-assist: Colon Health or one of two controls (usual care plus or usual care). Trial participants are average-risk, aged 50-75 years, due for CRC screening and received a physician order for stool testing or colonoscopy. Effectiveness will be evaluated by comparing screening use, as documented in the EHR, between trial enrollees in the e-assist: Colon Health and usual care plus (CRC screening information receipt) groups. Secondary outcomes include patient-perceived benefits of, barriers to and support for CRC screening and patient-reported CRC screening intent. The usual care group will be used to estimate screening use without intervention and programme impact at the population level. Differences in outcomes by study arm will be estimated with hierarchical logit models where patients are nested within physicians. Ethics and dissemination All trial aspects have been approved by the Institutional Review Board of the health system in which the trial is being conducted. We will disseminate findings in diverse scientific venues and will target clinical and quality improvement audiences via other venues. The intervention could serve as a model for filling the gap between physician recommendations and patient action. Trial registration number NCT02798224; Pre-results.
    • Rapamycin re-directs lysosome network, stimulates er-remodeling, involving membrane CD317 and affecting exocytosis, in Campylobacter Jejuni-lysate-infected U937 cells

      Canonico, B; Cesarini, E; Montanari, M; Di Sario, G; Campana, R; Galluzzi, L; Sola, F; Gundogdu, O; Luchetti, F; Diotallevi, A; Baffone, W; Giordano, A; Papa, S; Giordano, Antonio|0000-0002-5959-016X (2020-03-02)
      © 2020 by the authors. Licensee MDPI, Basel, Switzerland. The Gram-negative Campylobacter jejuni is a major cause of foodborne gastroenteritis in humans worldwide. The cytotoxic effects of Campylobacter have been mainly ascribed to the actions of the cytolethal distending toxin (CDT): it is mandatory to put in evidence risk factors for sequela development, such as reactive arthritis (ReA) and Guillain-Barré syndrome (GBS). Several researches are directed to managing symptom severity and the possible onset of sequelae. We found for the first time that rapamycin (RM) is able to largely inhibit the action of C. jejuni lysate CDT in U937 cells, and to partially avoid the activation of specific sub-lethal effects. In fact, we observed that the ability of this drug to redirect lysosomal compartment, stimulate ER-remodeling (highlighted by ER–lysosome and ER–mitochondria contacts), protect mitochondria network, and downregulate CD317/tetherin, is an important component of membrane microdomains. In particular, lysosomes are involved in the process of the reduction of intoxication, until the final step of lysosome exocytosis. Our results indicate that rapamycin confers protection against C. jejuni bacterial lysate insults to myeloid cells.
    • RBL2/p130: a direct AKT substrate and mediator of AKT inhibition-induced apoptosis

      Ventura, Elisa; Pentimalli, Francesca; Giordano, Antonio; Giordano, Antonio|0000-0002-5959-016X (2018-08-28)
    • Real World Food Justice and the Enigma of the Scholar-Activist Label: A Reflection on Research Values

      Croog, Rebecca; Hayes-Conroy, Allison; Gutiérrez-Vélez, Víctor Hugo; Saenz-Montoya, Alexis (2018-10-04)
      Engaging Kate Derickson and Paul Routledge’s set of papers on scholar-activism, this paper reflects on what sorts of research values inspire and accompany scholar-activist research. We draw on multiple examples from research in Colombia and the United States, each of which speaks to the theme of food justice, broadly conceived. We pay attention to research “wants and needs,” finding that specific outcomes (such as usable or compelling data) are only part of a wider array of desires and obligations that make scholar-activist partnerships valuable. Our examples demonstrate four distinct research values— supportive networks, active science, productive discomfort, and affective moments, —that form a vision of scholar-activism that blurs the boundaries between research, political realities, and everyday lives, and seeks to confront real world challenges. The emphasis on active science is as intentional as it is surprising; scholar-activism has been pigeonholed by mainstream academia as a kind of research that doesn’t square well with scientific outcomes. Meanwhile, interdisciplinarity and transdisciplinarity are being espoused as essential to solving contemporary problems. Thus, we emphasize that the knowledge, skills and values gained through broad engagement between scholar-activists and others in and out of academia can make scientific inquiry more socially relevant.
    • Real-Time Loop-Mediated Isothermal Amplification (RealAmp) for the Species-Specific Identification of Plasmodium vivax

      Patel, JC; Oberstaller, J; Xayavong, M; Narayanan, J; DeBarry, JD; Srinivasamoorthy, G; Villegas, L; Escalante, AA; DaSilva, A; Peterson, DS; Barnwell, JW; Kissinger, JC; Udhayakumar, V; Lucchi, NW (2013-01-29)
      Plasmodium vivax infections remain a major source of malaria-related morbidity and mortality. Early and accurate diagnosis is an integral component of effective malaria control programs. Conventional molecular diagnostic methods provide accurate results but are often resource-intensive, expensive, have a long turnaround time and are beyond the capacity of most malaria-endemic countries. Our laboratory has recently developed a new platform called RealAmp, which combines loop-mediated isothermal amplification (LAMP) with a portable tube scanner real-time isothermal instrument for the rapid detection of malaria parasites. Here we describe new primers for the detection of P. vivax using the RealAmp method. Three pairs of amplification primers required for this method were derived from a conserved DNA sequence unique to the P. vivax genome. The amplification was carried out at 64°C using SYBR Green or SYTO-9 intercalating dyes for 90 minutes with the tube scanner set to collect fluorescence signals at 1-minute intervals. Clinical samples of P. vivax and other human-infecting malaria parasite species were used to determine the sensitivity and specificity of the primers by comparing with an 18S ribosomal RNA-based nested PCR as the gold standard. The new set of primers consistently detected laboratory-maintained isolates of P. vivax from different parts of the world. The primers detected P. vivax in the clinical samples with 94.59% sensitivity (95% CI: 87.48-98.26%) and 100% specificity (95% CI: 90.40-100%) compared to the gold standard nested-PCR method. The new primers also proved to be more sensitive than the published species-specific primers specifically developed for the LAMP method in detecting P. vivax.
    • Reasons low-income parents offer snacks to children: How feeding rationale influences snack frequency and adherence to dietary recommendations

      Blaine, RE; Fisher, JO; Taveras, EM; Geller, AC; Rimm, EB; Land, T; Perkins, M; Davison, KK (2015-07-21)
      © 2015 by the authors; licensee MDPI, Basel, Switzerland. Although American children snack more than ever before, the parental role in promoting snacking is not well understood. In 2012–2013 at baseline in an intervention study to prevent childhood obesity in low-income Massachusetts communities, n = 271 parents of children aged 2–12 years completed surveys regarding nutritive and non-nutritive reasons they offered children snacks, demographics, and dietary factors. An analysis of variance demonstrated that parents reported offering snacks (mean/week; standard deviation (SD)) for nutritive reasons like promoting growth (¯x = 2.5; SD 2.2) or satisfying hunger (¯x = 2.4; SD 2.1) almost twice as often as non-nutritive reasons like keeping a child quiet (¯x = 0.7; SD 1.5) or celebrating events/holidays (¯x = 0.8; SD 1.1). Parents reported giving young children (2–5 years) more snacks to reward behavior (1.9 vs. 1.1, p < 0.001), keep quiet (1.0 vs. 0.5, p < 0.001), and celebrate achievements (1.7 vs. 1.0, p < 0.001) than parents of older children (6–12 years). Multivariable logistic regression models were used to obtain adjusted odds ratios, which indicated reduced child adherence to dietary recommendations when parents offered snacks to reward behavior (Odds Ratio (OR) = 0.83; 95% Confidence Interval (CI) 0.70–0.99), celebrate events/holidays (OR = 0.72; 95% CI 0.52–0.99), or achievements (OR = 0.82; 95% CI 0.68–0.98). Parental intentions around child snacking are likely important targets for obesity prevention efforts.
    • Recovering an Ars Moriendi

      Catholic Medical Association (2013-11-01)
    • Recovery of an oxidized majorite inclusion from Earth's deep asthenosphere

      Xu, Cheng; Kynicky, Jindrich; Tao, Renbiao; Liu, Xi; Zhang, Lifei; Pohanka, Miroslav; Song, Wenlei; Fei, Yingwei; Tao, Rongjia|0000-0001-5058-4401 (2017-04)
      Minerals recovered from the deep mantle provide a rare glimpse into deep Earth processes. We report the first discovery of ferric iron-rich majoritic garnet found as inclusions in a host garnet within an eclogite xenolith originating in the deep mantle. The composition of the host garnet indicates an ultrahigh-pressure metamorphic origin, probably at a depth of ~200 km. More importantly, the ferric iron-rich majoritic garnet inclusions show a much deeper origin, at least at a depth of 380 km. The majoritic nature of the inclusions is confirmed by mineral chemistry, x-ray diffraction, and Raman spectroscopy, and their depth of origin is constrained by a new experimental calibration. The unique relationship between the majoritic inclusions and their host garnet has important implications for mantle dynamics within the deep asthenosphere. The high ferric iron content of the inclusions provides insights into the oxidation state of the deep upper mantle.
    • Recruiting Community partners for Veggie Van: Strategies and lessons learned from a mobile market intervention in North Carolina, 2012-2015

      Tripicchio, GL; Smith, JG; Armstrong-Brown, J; McGuirt, J; Haynes-Maslow, L; Mardovich, S; Ammerman, AS; Leone, L (2017-04-01)
      Background Food access interventions are promising strategies for improving dietary intake, which is associated with better health. However, studies examining the relationship between food access and intake are limited to observational designs, indicating a need for more rigorous approaches. The Veggie Van (VV) program was a cluster-randomized intervention designed to address the gap between food access and intake. In this article, we aim to describe the approaches involved in recruiting community partners to participate in VV. Community Context The VV mobile market aimed to improve access to fresh fruits and vegetables by providing subsidized, high-quality, local produce in low-resource communities in North Carolina. This study describes the strategies and considerations involved in recruiting community partners and individual participants for participation in the VV program and evaluation. Methods To recruit partners, we used various strategies, including a site screener to identify potential partners, interest forms to gauge future VV use and prioritize enrollment of a high-need population, marketing materials to promote VV, site liaisons to coordinate community outreach, and a memorandum of understanding between all invested parties. Outcome A total of 53 community organizations and 725 participants were approached for recruitment. Ultimately, 12 sites and 201 participants were enrolled. Enrollment took 38 months, but our approaches helped successfully recruit a low-income, low-access population. The process took longer than anticipated, and funding constraints prevented certain strategies from being implemented. Interpretation Recruiting community partners and members for participation in a multi-level, community-based intervention was challenging. Strategies and lessons learned can inform future studies.
    • Redressing Jewish Difference in Tania Modleski's "Cinema and the Dark Continent"

      Levitt, Laura S. (1997-10)
      This essay addresses what Jewish Studies and Religion scholars have to contribute to cultural discourse about film. Through a careful reading of feminist critic Tania Modleski's essay, this article demonstrates some of the blindspots in film studies when it comes to depictions of Jews, Jewishness, and Judaism. By addressing the ambivalent status of Jewishness in Modleski's work, the essay offers another way of reading Jewishness in not only the Jazz Singer and Crossing Delancy, but in critical discourse more generally.
    • Reduced expression of MECP2 affects cell commitment and maintenance in neurons by triggering senescence: New perspective for Rett syndrome

      Squillaro, T; Alessio, N; Cipollaro, M; Melone, MAB; Hayek, G; Renieri, A; Giordano, A; Galderisi, U; Giordano, Antonio|0000-0002-5959-016X (2012-04-15)
      MECP2 protein binds preferentially to methylated CpGs and regulates gene expression by causing changes in chromatin structure. The mechanism by which impaired MECP2 activity can induce pathological abnormalities in the nervous system of patients with Rett syndrome (RTT) is not clearly understood. To gain further insight into the role of MECP2 in human neurogenesis, we compared the neural differentiation process in mesenchymal stem cells (MSCs) obtained from a RTT patient and from healthy donors. We further analyzed neural differentiation in a human neuroblastoma cell line carrying a partially silenced MECP2 gene. Senescence and reduced expression of neural markers were observed in proliferating and differentiating MSCs from the RTT patient, which suggests that impaired activity of MECP2 protein may impair neural differentiation, as observed in RTT patients. Next, we used an inducible expression system to silence MECP2 in neuroblastoma cells before and after the induction of neural differentiation via retinoic acid treatment. This approach was used to test whether MECP2 inactivation affected the cell fate of neural progenitors and/or neuronal differentiation and maintenance. Overall, our data suggest that neural cell fate and neuronal maintenance may be perturbed by senescence triggered by impaired MECP2 activity either before or after neural differentiation. © 2012 Squillaro et al.
    • Reference-Free Comparative Genomics of 174 Chloroplasts

      Kua, CS; Ruan, J; Harting, J; Ye, CX; Helmus, MR; Yu, J; Cannon, CH; Helmus, Matthew|0000-0003-3977-0507 (2012-11-27)
      Direct analysis of unassembled genomic data could greatly increase the power of short read DNA sequencing technologies and allow comparative genomics of organisms without a completed reference available. Here, we compare 174 chloroplasts by analyzing the taxanomic distribution of short kmers across genomes [1]. We then assemble de novo contigs centered on informative variation. The localized de novo contigs can be separated into two major classes: tip = unique to a single genome and group = shared by a subset of genomes. Prior to assembly, we found that ~18% of the chloroplast was duplicated in the inverted repeat (IR) region across a four-fold difference in genome sizes, from a highly reduced parasitic orchid [2] to a massive algal chloroplast [3], including gnetophytes [4] and cycads [5]. The conservation of this ratio between single copy and duplicated sequence was basal among green plants, independent of photosynthesis and mechanism of genome size change, and different in gymnosperms and lower plants. Major lineages in the angiosperm clade differed in the pattern of shared kmers and de novo contigs. For example, parasitic plants demonstrated an expected accelerated overall rate of evolution, while the hemi-parasitic genomes contained a great deal more novel sequence than holo-parasitic plants, suggesting different mechanisms at different stages of genomic contraction. Additionally, the legumes are diverging more quickly and in different ways than other major families. Small duplicated fragments of the rrn23 genes were deeply conserved among seed plants, including among several species without the IR regions, indicating a crucial functional role of this duplication. Localized de novo assembly of informative kmers greatly reduces the complexity of large comparative analyses by confining the analysis to a small partition of data and genomes relevant to the specific question, allowing direct analysis of next-gen sequence data from previously unstudied genomes and rapid discovery of informative candidate regions. © 2012 Kua et al.
    • Refugee Roulette: Disparities in Asylum Adjudication

      Schoenholtz, Andrew I.; Ramji-Nogales, Jaya; Schrag, Philip G. (2010-04)
      Addressing consistency in the application of the law, former Attorney General Robert Jackson told Congress in 1940: “It is obviously repugnant to one's sense of justice that the judgment meted out . . . should depend in large part on a purely fortuitous circumstance; namely the personality of the particular judge before whom the case happens to come for disposition.” Yet in asylum cases, which can spell the difference between life and death, the outcome apparently depends in large measure on which government official decides the claim. In many cases, the most important moment in an asylum case is the instant in which a clerk randomly assigns an application to a particular asylum officer or immigration judge.This study analyzes databases of decisions from all four levels of the asylum adjudication process: 133,000 decisions involving nationals from eleven key countries rendered by 884 asylum officers over a seven-year period; 140,000 decisions of 225 immigration judges over a four-and-a-half-year period; 126,000 decisions of the Board of Immigration Appeals over a six-year period; and 4215 decisions of the U.S. courts of appeals during 2004 and 2005. The analysis reveals amazing disparities in grant rates, even when different adjudicators in the same office each considered large numbers of applications from nationals of the same country. For example, in one regional asylum office, 60% of the officers decided in favor of Chinese applicants at rates that deviated by more than 50% from that region's mean grant rate for Chinese applicants, with some officers granting asylum to no Chinese nationals, while other officers granted asylum in as many as 68% of their cases. Similarly, Colombian asylum applicants whose cases were adjudicated in the federal immigration court in Miami had a 5% chance of prevailing with one of that court's judges and an 88% chance of prevailing before another judge in the same building. Half of the Miami judges deviated by more than 50% from the court's mean grant rate for Colombian cases.Using cross-tabulations based on public biographies, the paper also explores correlations between sociological characteristics of individual immigration judges and their grant rates. The cross-tabulations show that the chance of winning asylum was strongly affected not only by the random assignment of a case to a particular immigration judge, but also in very large measure by the quality of an applicant's legal representation, by the gender of the immigration judge, and by the immigration judge's work experience prior to appointment.In their conclusion, the authors do not recommend enforced quota systems for asylum adjudicators, but they do make recommendations for more comprehensive training, more effective and independent appellate review, and other reforms that would further professionalize the adjudication system.
    • Regulation of the HIV-1 promoter by HIF-1 and Vpr proteins

      Deshmane, SL; Amini, S; Sen, S; Khalili, K; Sawaya, BE (2011-10-25)
      We previously demonstrated the ability of HIV-1 Vpr protein to activate the oxidative stress pathway, thus leading to the induction of the hypoxia inducible factor 1 alpha (HIF-1). Therefore, we sought to examine the interplay between the two proteins and the impact of HIF-1 activation on HIV-1 transcription. Using transient transfection assays, we identified the optimal concentration of HIF-1 necessary for the activation of the HIV-1 promoter as well as the domain within HIF-1 responsible for this activation. Our findings indicated that activation of the HIV-1 LTR by Vpr is HIF-1 dependent. Furthermore, we showed that both Vpr and HIF-1 activate the HIV-1 promoter through the GC-rich binding domain within the LTR. Taken together, these data shed more light on the mechanisms used by Vpr to activate the HIV-1 promoter and placed HIF-1 as a major participant in this activation. © 2011 Deshmane et al; licensee BioMed Central Ltd.
    • Regulatory Blowout: How Regulatory Failures Made the BP Disaster Possible, and How the System Can Be Fixed to Avoid a Recurrence

      The Center for Progressive Reform (2010-10)
      The BP oil spill in the Gulf of Mexico is destined to take its place as one of the greatest environmental disasters in the history of the United States, or for that matter, of the entire planet. Like so many other disasters on that list, it was entirely preventable. BP must shoulder its share of the blame, of course. Similarly, the Minerals Management Service (MMS) – since reorganized and rebranded – has come under much deserved criticism for its failure to rein in BP’s avaricious approach to drilling even where it was unable to respond to a worst-case scenario in a responsible and timely fashion. But the problems run much deeper than a single risk-taking company and a single dysfunctional regulatory agency. This report sketches out widespread regulatory failure, touching several agencies of the federal government and affecting several critical environmental statutes. Prepared by Member Scholars of the Center for Progressive Reform (CPR), it has two goals: (1) to identify how and why the regulatory system failed to protect the public and environment and prevent the BP disaster, and (2) to recommend the priority reforms that are essential to correct these regulatory deficiencies. The report begins by laying out the shortcomings in the primary statute under which deepwater oil drilling is regulated – the Outer Continental Shelf Lands Act (OCSLA) – and outlines key reforms needed to provide the authority necessary to protect the public interest. It then turns to systemic problems within the agency charged with regulation of deepwater oil drilling under the OCSLA – the Mineral Management Service (MMS), renamed the Bureau of Ocean Energy Management, Regulation and Enforcement (BOEMRE) in the wake of the disaster. These include problems of agency capture and inadequate funding. The third topic addressed in the report is the role of the National Environmental Policy Act (NEPA) – how and why this landmark statute was disabled from performing its critical role in the case of the BP well, and what regulatory changes can ensure that it functions effectively in the future. The report next details the problems that surrounded the implementation and enforcement of the Endangered Species Act (ESA) as it applied to oil drilling and recommends several key reforms. The report then discusses a systemic problem that is a theme in each prior section and that specific statutory reforms cannot fully remedy: obstacles to making sound regulatory decisions in the face of uncertain, low probability risks of potentially catastrophic or irreversible harm. This section highlights a common sense solution: adoption of a precautionary stance. A precautionary approach would replace the current widely-adopted presumption that regulation must await a high – and often unattainable – degree of certainty, even when the potential costs are irreversible or catastrophic. In the last sections of the report, we step back to look at the regulatory system from a broader perspective. We consider first how the regulatory system and its failures in this case were caused in part by the absence of coherent policies on energy and climate change. Our current policy provides vast incentives for risky oil and gas development like deepwater drilling and few for low-carbon alternative energy sources. In the wake of yet another painful lesson on the cost of our current incoherent approach, it is time to focus political attention on the difficult but necessary task of debating and adopting a coherent and sound energy policy. In the final section, we step back geographically to suggest why another lesson of this disaster is that the United States should undertake to learn more from the experience abroad, offering the example of the North Sea. Had we been paying closer attention, the investigations and reforms in the wake of the infamous Piper Alpha spill or the Bravo platform blowout might have offered insights to help us avoid this disaster.