Barriers and Bridges: An Action Plan for Overcoming Obstacles and Unlocking Opportunities for African American Men in Pittsburgh

Among the region's residents, Pittsburgh's African American men have historically and disproportionately faced unprecedented barriers to economic opportunities. This study, supported by The Heinz Endowments, focuses on structural barriers that contribute to persistent racial disparities in the Pittsburgh region. Structural barriers are obstacles that collectively affect a group disproportionately and perpetuate or maintain stark disparities in outcomes. Structural barriers can be policies, practices, and other norms that favor an advantaged group while systematically disadvantaging a marginalized group. A community touched by racebased structural barriers can be identified by the racial and economic stratification of its residents; Pittsburgh, like many large cities in the United States, fits that description

Potential Corrosion Issue in CO2 Pipeline

In this paper we investigate the increasing atmospheric concentration of carbon dioxide originating from human activities which include burning fossil fuels for heat and electricity generation, and combustion of other fuels in industry lead to greenhouse gases (GHG) mainly CO2 which has an impact on the global climate warming. It is necessary to scale down the impact of these gases on the global climate by minimizing or preventing greenhouse gas emission to the atmosphere. Carbon capture and storage (CCS) from the source or power plant will help in reducing the emission of CO2 from the atmosphere with the means of transporting the gas through the pipeline from the captured sources or power plant to storage sites underground or for enhanced oil recovery (EOR). However, this gas has some contaminant or impurities which affect the mechanical and chemical properties of the pipeline system during transportation. This paper examines various contaminants such as CO2, H2S, CO, NOX, SOX, and H2O in carbon dioxide transmission pipelines with a particular focus on assessing how the contaminants causes corrosion in the pipeline and also considered materials that can be used as alternative to carbon steel for CO2 transportation pipeline. The materials examined ranges from weldable 13%Cr super modified martensitic stainless steel, 22%Cr duplex and 25% Cr super duplex stainless steel, 316L clad pipe or Lined carbon steel and nickel alloy, and some parameters in materials selection were examined. The alternative materials considered are 13 %Cr super-modified martensitic stainless steel, and 25 %Cr super-duplex stainless steel. Keywords: CO2 Corrosion, CO2 Contaminant, Material Selection. DOI: 10.7176/JEP/10-12-19 Publication date: April 30th 201

Science Theater as STEAM: A Case Study of Save It Now

What are the markers of a successful STEAM program? How and when can educators be reasonably sure that an interdisciplinary unit or project, rich in both the sciences and the arts, has delivered on its implicit promise – by adding value to a student’s education in ways that are beyond the scope of traditional discipline-specific learning? I attempt to address this question with a case study of Theatre of Will’s “Save It Now,” a pilot program for 4th, 5th and 6th graders at eight Los Angeles public schools that integrates theater arts, music and the STEM disciplines in a 9-week unit on energy, water and climate change. I am one of the program’s four teaching artists. My goal here is not to convince readers that “Save it Now” is successful, but rather to propose a theoretical framework for understanding, categorizing and evaluating STEAM programs in general. theatreofwill.or

Uncovering the reciprocal complementarity between product and process innovation

© 2016, Elsevier. The attached document (embargoed until 17/02/2019) is an author produced version of a paper published in RESEARCH POLICY uploaded in accordance with the publisher’s self- archiving policy. The final published version (version of record) is available online at the link below. Some minor differences between this version and the final published version may remain. We suggest you refer to the final published version should you wish to cite from it

Inhibition of the PI3K/AKT/mTOR pathway activates autophagy and compensatory Ras/Raf/MEK/ERK signalling in prostate cancer

The PI3K/AKT/mTOR pathway is frequently activated in advanced prostate cancer, due to loss of the tumour suppressor PTEN, and is an important axis for drug development. We have assessed the molecular and functional consequences of pathway blockade by inhibiting AKT and mTOR kinases either in combination or as individual drug treatments. In established prostate cancer cell lines, a decrease in cell viability and in phospho-biomarker expression was observed. Although apoptosis was not induced, a G1 growth arrest was observed in PTEN null LNCaP cells, but not in BPH1 or PC3 cells. In contrast, when the AKT inhibitor AZD7328 was applied to patient-derived prostate cultures that retained expression of PTEN, activation of a compensatory Ras/MEK/ERK pathway was observed. Moreover, whilst autophagy was induced following treatment with AZD7328, cell viability was less affected in the patient-derived cultures than in cell lines. Surprisingly, treatment with a combination of both AZD7328 and two separate MEK1/2 inhibitors further enhanced phosphorylation of ERK1/2 in primary prostate cultures. However, it also induced irreversible growth arrest and senescence.Ex vivo treatment of a patient-derived xenograft (PDX) of prostate cancer with a combination of AZD7328 and the mTOR inhibitor KU-0063794, significantly reduced tumour frequency upon re-engraftment of tumour cells.The results demonstrate that single agent targeting of the PI3K/AKT/mTOR pathway triggers activation of the Ras/MEK/ERK compensatory pathway in near-patient samples. Therefore, blockade of one pathway is insufficient to treat prostate cancer in man

Chemotactic response and adaptation dynamics in Escherichia coli

Adaptation of the chemotaxis sensory pathway of the bacterium Escherichia coli is integral for detecting chemicals over a wide range of background concentrations, ultimately allowing cells to swim towards sources of attractant and away from repellents. Its biochemical mechanism based on methylation and demethylation of chemoreceptors has long been known. Despite the importance of adaptation for cell memory and behavior, the dynamics of adaptation are difficult to reconcile with current models of precise adaptation. Here, we follow time courses of signaling in response to concentration step changes of attractant using in vivo fluorescence resonance energy transfer measurements. Specifically, we use a condensed representation of adaptation time courses for efficient evaluation of different adaptation models. To quantitatively explain the data, we finally develop a dynamic model for signaling and adaptation based on the attractant flow in the experiment, signaling by cooperative receptor complexes, and multiple layers of feedback regulation for adaptation. We experimentally confirm the predicted effects of changing the enzyme-expression level and bypassing the negative feedback for demethylation. Our data analysis suggests significant imprecision in adaptation for large additions. Furthermore, our model predicts highly regulated, ultrafast adaptation in response to removal of attractant, which may be useful for fast reorientation of the cell and noise reduction in adaptation.Comment: accepted for publication in PLoS Computational Biology; manuscript (19 pages, 5 figures) and supplementary information; added additional clarification on alternative adaptation models in supplementary informatio

Photoaffinity cross-linking and unnatural amino acid mutagenesis reveal insights into calcitonin gene-related peptide binding to the calcitonin receptor-like receptor/receptor activity-modifying protein 1 (CLR/RAMP1) complex

Calcitonin gene-related peptide (CGRP) binds to the complex of the calcitonin receptor-like receptor (CLR) with receptor activity-modifying protein 1 (RAMP1). How CGRP interacts with the transmembrane domain (including the extracellular loops) of this family B receptor remains unclear. In this study, a photoaffinity cross-linker, p-azido l-phenylalanine (azF), was incorporated into CLR, chiefly in the second extracellular loop (ECL2) using genetic code expansion and unnatural amino acid mutagenesis. The method was optimized to ensure efficient photolysis of azF residues near the transmembrane bundle of the receptor. A CGRP analogue modified with fluorescein at position 15 was used for detection of ultraviolet-induced cross-linking. The methodology was verified by confirming the known contacts of CGRP to the extracellular domain of CLR. Within ECL2, the chief contacts were I284 on the loop itself and L291, at the top of the fifth transmembrane helix (TM5). Minor contacts were noted along the lip of ECL2 between S286 and L290 and also with M223 in TM3 and F349 in TM6. Full length molecular models of the bound receptor complex suggest that CGRP sits at the top of the TM bundle, with Thr6 of the peptide making contacts with L291 and H295. I284 is likely to contact Leu12 and Ala13 of CGRP, and Leu16 of CGRP is at the ECL/extracellular domain boundary of CLR. The reduced potency, Emax, and affinity of [Leu16Ala]-human α CGRP are consistent with this model. Contacts between Thr6 of CGRP and H295 may be particularly important for receptor activation

Immunochip analysis identifies multiple susceptibility loci for systemic sclerosis

In this study, 1,833 systemic sclerosis (SSc) cases and 3,466 controls were genotyped with the Immunochip array. Classical alleles, amino acid residues, and SNPs across the human leukocyte antigen (HLA) region were imputed and tested. These analyses resulted in a model composed of six polymorphic amino acid positions and seven SNPs that explained the observed significant associations in the region. In addition, a replication step comprising 4,017 SSc cases and 5,935 controls was carried out for several selected non-HLA variants, reaching a total of 5,850 cases and 9,401 controls of European ancestry. Following this strategy, we identified and validated three SSc risk loci, including DNASE1L3 at 3p14, the SCHIP1-IL12A locus at 3q25, and ATG5 at 6q21, as well as a suggested association of the TREH-DDX6 locus at 11q23. The associations of several previously reported SSc risk loci were validated and further refined, and the observed peak of association in PXK was related to DNASE1L3. Our study has increased the number of known genetic associations with SSc, provided further insight into the pleiotropic effects of shared autoimmune risk factors, and highlighted the power of dense mapping for detecting previously overlooked susceptibility loci