2,095 research outputs found

    Advancing Frontline Employees of Color

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    Employers of frontline talent face an unprecedented opportunity to advance racial equity as a source of competitive advantage. The United States is experiencing dramatic demographic shifts, its workforce is becoming increasingly racially diverse, and the nature of work is fundamentally changing due to automation. Approximately nine million of the country's 24 million frontline employees—entry-level employees who engage closely with customers—are people of color who represent a reservoir of talent, innovative ideas, and multicultural competency that are increasingly sources of competitive advantage.At a time when there are rising societal expectations for companies to embrace a more active role in society and lead with an ambitious corporate purpose, employers face an unprecedented opportunity to advance racial equity as a source of competitive advantage by intentionally finding ways to advance the careers and enhance the experience of employees of color.Advancing Frontline Employees of Color, written in partnership with PolicyLink, identifies 23 evidence-based practices for advancing racial equity and fostering working environments where all people feel valued and can thrive

    Assessing the Awareness of Lead Hazards in the Greater Burlington Area

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    Introduction. Lead is a heavy metal found in and around homes built before 1978, comprising more than 80% of the housing stock in Chittenden County, Vermont. Lead exposure during infancy and childhood can have deleterious effects on development. Our study assessed baseline community understanding of potential household lead hazards in Chittenden County, Vermont. Methods.. 123 paper, 10-question surveys were randomly administered to Chittenden County, VT residents to assess recognition of lead toxicology symptoms and awareness of lead safety programs. Scores were treated as continuous variables, demographically grouped, and analyzed using non-parametric statistical analysis (Mann-Whitney & Kruskal-Wallis). Individual questions were treated as dichotomous variables, demographically grouped and analyzed using chi-squared testing. Results.. 48% of survey participants understood the interaction between ADHD and lead or knew the importance of window maintenance. 54.5% were aware of the Burlington Lead Program\u27s assistance program. Participants earning less than $60,000 and those with less than a graduate degree scored statistically lower (p Conclusion.. Lesser-known lead poisoning symptoms and home interventions that decrease lead exposure should be emphasized to the community. High-risk groups requiring targeted education include those who rent, have lower income and education levels. Primary care providers could serve a larger role in educating patients. Additional efforts should be made to publicize services offered by the Burlington Lead Program.https://scholarworks.uvm.edu/comphp_gallery/1241/thumbnail.jp

    Lost and found: Coffea stenophylla and C. affinis, the forgotten coffee crop species of west Africa

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    Two species, Coffea arabica and C. canephora, are used to produce the world’s coffee, and serve the coffee sector admirably. However, various challenges at the production (farm) level, including the increasing prevalence and severity of disease and pests and climate change, indicate that the coffee crop portfolio needs to be diversified in order to ensure resilience and sustainability. In this study we use a multidisciplinary approach (herbarium and literature review, fieldwork and DNA sequencing) to elucidate the taxonomic identities, agronomic attributes and whereabouts of two poorly known coffee crop species, C. affinis and C. stenophylla. We show that despite widespread, albeit small-scale, use as a coffee crop species across Upper West Africa, (and further afield) more than 100 years ago , these species are now rare in the wild and in cultivation. Fieldwork enabled us to rediscover C. stenophylla in Sierra Leone, which previously had not been recorded in the wild there since 1954. We confirm that C. stenophylla is an indigenous species in Guinea, Sierra Leone, and Ivory Coast, and show that C. affinis is indigenous in Guinea and Ivory Coast. Both species are likely to be threatened with extinction in the wild, particularly in Guinea. DNA sequencing using plastid and ITS markers was used to: confirm the identity of museum and field collected samples of C. stenophylla; demonstrate the use of plastid and nuclear markers to identify F1 and early-generation interspecific hybrids; identify the hybrid C. liberica x C. stenophylla; and reveal that C. liberica is non-monophyletic and likely to represent more than one species. Contrary to contemporary opinion, we could find no evidence of hybrid status for C. affinis, although the taxonomic identity of this species remains unclear. Sequencing analyses also show that hybridization is possible across all the major short-styled Africa Coffea species, i.e. Coffee Crop Wild Relative Priority Groups I and II. Coffea affinis and C. stenophylla may possess traits useful for coffee crop plant development, including taste differentiation, disease resistance, and climate resilience; these attributes would be best accessed via breeding programmes although these two species may have potential as crops with minimal domestication

    Computationally Designed Bispecific Antibodies using Negative State Repertoires

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    A challenge in the structure-based design of specificity is modeling the negative states, i.e., the complexes that you do not want to form. This is a difficult problem because mutations predicted to destabilize the negative state might be accommodated by small conformational rearrangements. To overcome this challenge, we employ an iterative strategy that cycles between sequence design and protein docking in order to build up an ensemble of alternative negative state conformations for use in specificity prediction. We have applied our technique to the design of heterodimeric CH3 interfaces in the Fc region of antibodies. Combining computationally and rationally designed mutations produced unique designs with heterodimer purities greater than 90%. Asymmetric Fc crystallization was able to resolve the interface mutations; the heterodimer structures confirmed that the interfaces formed as designed. With these CH3 mutations, and those made at the heavy-/light-chain interface, we demonstrate one-step synthesis of four fully IgG-bispecific antibodies

    Phase 1 Trial of Malaria Transmission Blocking Vaccine Candidates Pfs25 and Pvs25 Formulated with Montanide ISA 51

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    Pfs25 and Pvs25, surface proteins of mosquito stage of the malaria parasites P. falciparum and P. vivax, respectively, are leading candidates for vaccines preventing malaria transmission by mosquitoes. This single blinded, dose escalating, controlled Phase 1 study assessed the safety and immunogenicity of recombinant Pfs25 and Pvs25 formulated with Montanide ISA 51, a water-in-oil emulsion.The trial was conducted at The Johns Hopkins Center for Immunization Research, Washington DC, USA, between May 16, 2005-April 30, 2007. The trial was designed to enroll 72 healthy male and non-pregnant female volunteers into 1 group to receive adjuvant control and 6 groups to receive escalating doses of the vaccines. Due to unexpected reactogenicity, the vaccination was halted and only 36 volunteers were enrolled into 4 groups: 3 groups of 10 volunteers each were immunized with 5 microg of Pfs25/ISA 51, 5 microg of Pvs25/ISA 51, or 20 microg of Pvs25/ISA 51, respectively. A fourth group of 6 volunteers received adjuvant control (PBS/ISA 51). Frequent local reactogenicity was observed. Systemic adverse events included two cases of erythema nodosum considered to be probably related to the combination of the antigen and the adjuvant. Significant antibody responses were detected in volunteers who completed the lowest scheduled doses of Pfs25/ISA 51. Serum anti-Pfs25 levels correlated with transmission blocking activity.It is feasible to induce transmission blocking immunity in humans using the Pfs25/ISA 51 vaccine, but these vaccines are unexpectedly reactogenic for further development. This is the first report that the formulation is associated with systemic adverse events including erythema nodosum.ClinicalTrials.gov NCT00295581

    Insertion of heterometals into the NifEN-associated iron–molybdenum cofactor precursor

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    The cofactors of Mo-, V-, Fe-dependent nitrogenases are believed to be highly homologous in structure despite the different types of heterometals (Mo, V, and Fe) they contain. Previously, a precursor form of the FeMo cofactor (FeMoco) was captured on NifEN, a scaffold protein for FeMoco biosynthesis. This all-Fe precursor closely resembles the Fe/S core structure of the FeMoco and, therefore, could reasonably serve as a precursor for all nitrogenase cofactors. Here, we report the heterologous incorporation of V and Fe into the NifEN-associated FeMoco precursor. EPR and activity analyses indicate that V and Fe can be inserted at much reduced efficiencies compared with Mo, and incorporation of both V and Fe is enhanced in the presence of homocitrate. Further, native polyacrylamide gel electrophoresis experiments suggest that NifEN undergoes a significant conformational rearrangement upon metal insertion, which allows the subsequent NifEN–MoFe protein interactions and the transfer of the cofactor between the two proteins. The combined outcome of these in vitro studies leads to the proposal of a selective mechanism that is utilized in vivo to maintain the specificity of heterometals in nitrogenase cofactors, which is likely accomplished through the redox regulation of metal mobilization by different Fe proteins (encoded by nifH, vnfH, and anfH, respectively), as well as the differential interactions between these Fe proteins and their respective scaffold proteins (NifEN and VnfEN) in the Mo-, V-, and Fe-dependent nitrogenase systems

    Variable-temperature, variable-field magnetic circular dichroism spectroscopic study of NifEN-bound precursor and “FeMoco”

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    NifEN plays a key role in the biosynthesis of the iron–molybdenum cofactor (FeMoco) of nitrogenase. A scaffold protein that hosts the conversion of a FeMoco precursor to a mature cofactor, NifEN can assume three conformations during the process of FeMoco maturation. One, designated ΔnifB NifEN, contains only two permanent [Fe4S4]-like clusters. The second, designated NifENPrecursor, contains the permanent clusters and a precursor form of FeMoco. The third, designated NifEN“FeMoco”, contains the permanent [Fe4S4]-like clusters and a fully complemented, “FeMoco”-like structure. Here, we report a variable-temperature, variable-field magnetic circular dichroism spectroscopic investigation of the electronic structure of the metal clusters in the three forms of dithionite-reduced NifEN. Our data indicate that the permanent [Fe4S4]-like clusters are structurally and electronically conserved in all three NifEN species and exhibit spectral features of classic [Fe4S4]+ clusters; however, they are present in a mixed spin state with a small contribution from the S > ½ spin state. Our results also suggest that both the precursor and “FeMoco” have a conserved Fe/S electronic structure that is similar to the electronic structure of FeMoco in the MoFe protein, and that the “FeMoco” in NifEN“FeMoco” exists, predominantly, in an S = 3/2 spin state with spectral parameters identical to those of FeMoco in the MoFe protein. These observations provide strong support to the outcome of our previous EPR and X-ray absorption spectroscopy/extended X-ray absorption fine structure analysis of the three NifEN species while providing significant new insights into the unique electronic properties of the precursor and “FeMoco” in NifEN
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