1,144 research outputs found

    Agricultural and Small Business Retirement Plans and Needs for Information: Evidence from a Vermont Survey

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    A survey of Vermont agricultural and small business owners and managers was conducted to examine their retirement plans and needs for information. Results from 828 respondents indicate that 42% of them do not have any retirement plan and 45% of the surveyed businesses do not offer any retirement plan for their employees. Results also suggest that most small business owners and managers who do not have a retirement plan are not very interested in more information on retirement planning.Consumer/Household Economics,

    A separating problem on function spaces

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    Distinguishing between unorganized and organized convection when examining land-atmosphere relationships

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    In this study, the robustness of a previously developed classification system that categorizes convective thunderstorm events initiated during various synoptic and dynamic conditions is analyzed. This classification system was used to distinguish between organized and unorganized convection and then used to determine whether unorganized convection occurs preferentially over wet or dry soils. The focus is on 12 events that occurred in synoptically benign (SB) environments where the Great Plains low-level jet was not present (noLLJ), and whether these events were accurately classified as unorganized convection is evaluated. Although there is a small sample size, the results show that the classification system fails to differentiate between local unorganized convection and large-scale organized convection under SB–noLLJ conditions. The authors conclude that past studies that have used this classification to study how soil moisture influences unorganized convection should be revisited. Additional variables and/or alternative precipitation datasets should be employed to enhance the robustness of the classification system

    Exploration of relationships between safety performance and unsafe behavior in coal mining processes

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    PresentationIt is well known that safety performance is differentiated to two components, namely, safety compliance and safety participation. However, relationships between safety performance and unsafe behavior were barely explored. In this work, the scales for safety compliance and safety participation were slightly revised for usage in coal mining processes, and job burnout scale was developed on the basis of MBI-GS. Then, structural equation model was employed to investigate the interaction of these factors using samples of 367 front-line coal miners in large state-owned mining companies in China. The results show that individual unsafe behavior could not be diminished significantly by only focusing on these two dimensions of safety performance. Compared with safety participation, safety compliance has more significant influence on unsafe behavior, and job burnout is an indispensable moderator between these two components and unsafe behavior. More importantly, it is vital to pay close attention to employees’ occupational psychological health problem for improving organizational safety management and promoting personal performance

    Not so crystal clear: the structure of the human telomere G-quadruplex in solution differs from that present in a crystal

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    The structure of human telomere DNA is of intense interest because of its role in the biology of both cancer and aging. The sequence [5′-AGGG(TTAGGG)(3)] has been used as a model for telomere DNA in both NMR and X-ray crystallographic studies, the results of which show dramatically different structures. In Na(+) solution, NMR revealed an antiparallel G-quadruplex structure that featured both diagonal and lateral TTA loops. Crystallographic studies in the presence of K(+) revealed a flattened, propeller-shaped structure featuring a parallel-stranded G-quadruplex with symmetrical external TTA loops. We report the results of biophysical experiments in solution and computational studies that are inconsistent with the reported crystal structure, indicating that a different structure exists in K(+) solutions. Sedimentation coefficients were determined experimentally in both Na(+) and K(+) solutions and were compared with values calculated using bead models for the reported NMR and crystal structures. Although the solution NMR structure accurately predicted the observed S-value in Na(+) solution, the crystal structure predicted an S-value that differed dramatically from that experimentally observed in K(+) solution. The environments of loop adenines were probed by quantitative fluorescence studies using strategic and systematic single-substitutions of 2-aminopurine for adenine bases. Both fluorescence intensity and quenching experiments in K(+) yielded results at odds with quantitative predictions from the reported crystal structure. Circular dichroism and fluorescence quenching studies in the presence of the crowding agent polyethylene glycol showed dramatic changes in the quadruplex structure in K(+) solutions, but not in Na(+) solutions, suggesting that the crystal environment may have selected for a particular conformational form. Molecular dynamics simulations were performed to yield model structures for the K(+) quadruplex form that are consistent with our biophysical results and with previously reported chemical modification studies. These models suggest that the biologically relevant structure of the human telomere quadruplex in K(+) solution is not the one determined in the published crystalline state

    Periplasmic phosphorylation of lipid A is linked to the synthesis of undecaprenyl phosphate

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    One-third of the lipid A found in the Escherichia coli outer membrane contains an unsubstituted diphosphate unit at position 1 (lipid A 1-diphosphate). We now report an inner membrane enzyme, LpxT (YeiU), which specifically transfers a phosphate group to lipid A, forming the 1-diphosphate species. 32P-labelled lipid A obtained from lpxT mutants do not produce lipid A 1-diphosphate. In vitro assays with Kdo2-[4′-32P]lipid A as the acceptor shows that LpxT uses undecaprenyl pyrophosphate as the substrate donor. Inhibition of lipid A 1-diphosphate formation in wild-type bacteria was demonstrated by sequestering undecaprenyl pyrophosphate with the cyclic polypeptide antibiotic bacitracin, providing evidence that undecaprenyl pyrophosphate serves as the donor substrate within whole bacteria. LpxT-catalysed phosphorylation is dependent upon transport of lipid A across the inner membrane by MsbA, a lipid A flippase, indicating a periplasmic active site. In conclusion, we demonstrate a novel pathway in the periplasmic modification of lipid A that is directly linked to the synthesis of undecaprenyl phosphate, an essential carrier lipid required for the synthesis of various bacterial polymers, such as peptidoglycan

    Activation of PmrA inhibits LpxT-dependent phosphorylation of lipid A promoting resistance to antimicrobial peptides

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    During its transport to the bacterial surface, the phosphate groups of the lipid A anchor of Escherichia coli and Salmonella lipopolysaccharide are modified by membrane enzymes including ArnT, EptA and LpxT. ArnT and EptA catalyse the periplasmic addition of the positively charged substituents 4-amino-4-deoxy-L-arabinose and phosphoethanolamine respectively. These modifications are controlled by the PmrA transcriptional regulator and confer resistance to cationic antimicrobial peptides, including polymyxin. LpxT, however, catalyses the phosphorylation of lipid A at the 1-position forming 1-diphosphate lipid A increasing the negative charge of the bacterial surface. Here, we report that PmrA is involved in the regulation of LpxT. Interestingly, this regulation does not occur at the level of transcription, but rather following the assembly of LpxT into the inner membrane. PmrA-dependent inhibition of LpxT is required for phosphoethanolamine decoration of lipid A, which is shown here to be critical for E. coli to resist the bactericidal activity of polymyxin. Furthermore, although Salmonella lipid A is more prevalently modified with l-4-aminoarabinose, we demonstrate that loss of Salmonella lpxT greatly increases EptA modification. The current work is an example of the complexities associated with the structural remodelling of Gram-negative lipopolysaccharides promoting bacterial survival

    The Impact of Bayesian Hyperpriors on the Population-Level Eccentricity Distribution of Imaged Planets

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    Orbital eccentricities directly trace the formation mechanisms and dynamical histories of substellar companions. Here, we study the effect of hyperpriors on the population-level eccentricity distributions inferred for the sample of directly imaged substellar companions (brown dwarfs and cold Jupiters) from hierarchical Bayesian modeling (HBM). We find that the choice of hyperprior can have a significant impact on the population-level eccentricity distribution inferred for imaged companions, an effect that becomes more important as the sample size and orbital coverage decrease to values that mirror the existing sample. We reanalyse the current observational sample of imaged giant planets in the 5-100 AU range from Bowler et al. (2020) and find that the underlying eccentricity distribution implied by the imaged planet sample is broadly consistent with the eccentricity distribution for close-in exoplanets detected using radial velocities. Furthermore, our analysis supports the conclusion from that study that long-period giant planets and brown dwarf eccentricity distributions differ by showing that it is robust to the choice of hyperprior. We release our HBM and forward modeling code in an open-source Python package, ePop!, and make it freely available to the community.Comment: 18 pages, 11 figures. Accepted for publication in The Astronomical Journa

    Impact of Arsenic Species on Self-Assembly of Triangular and Hexagonal Tensile-Strained GaAs(111)A Quantum Dots

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    We use dimeric arsenic (As2) or tetrameric arsenic (As4) during molecular beam epitaxy to manipulate the structural and optical properties of GaAs(111)A tensile-strained quantum dots (TSQDs). Choice of arsenic species affects nucleation and growth behavior during TSQD self-assembly. Previously, epitaxial GaAs(111)A TSQDs have been grown with As4, producing TSQDs with a triangular base, and \u27A-step\u27 edges perpendicular to the three 1̅1̅2 directions. We demonstrate that using As2 at low substrate temperature also results in triangular GaAs(111)A TSQDs, but with \u27B-step\u27 edges perpendicular to the three 112̅ directions. We can therefore invert the crystallographic orientation of these triangular nanostructures, simply by switching between As4 and As2. At higher substrate temperatures, GaAs(111)A TSQDs grown under As2 develop with a hexagonal base. Compared with triangular dots, the higher symmetry of hexagonal TSQDs may reduce fine-structure splitting on this (111) surface, a requirement for robust photon entanglement. Regardless of shape, GaAs(111)A TSQDs grown under As2 exhibit superior optical quality

    TFEB is a master regulator of tumor-associated macrophages in breast cancer

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    BACKGROUND: Tumor-associated macrophages (TAMs) play key roles in the development of many malignant solid tumors including breast cancer. They are educated in the tumor microenvironment (TME) to promote tumor growth, metastasis, and therapy resistance. However, the phenotype of TAMs is elusive and how to regulate them for therapeutic purpose remains unclear; therefore, TAM-targeting therapies have not yet achieved clinical success. The purposes of this study were to examine the role of transcription factor EB (TFEB) in regulating TAM gene expression and function and to determine if TFEB activation can halt breast tumor development. METHODS: Microarrays were used to analyze the gene expression profile of macrophages (MΦs) in the context of breast cancer and to examine the impact of TFEB overexpression. Cell culture studies were performed to define the mechanisms by which TFEB affects MΦ gene expression and function. Mouse studies were carried out to investigate the impact of MΦ TFEB deficiency or activation on breast tumor growth. Human cancer genome data were analyzed to reveal the prognostic value of TFEB and its regulated genes. RESULTS: TAM-mimic MΦs display a unique gene expression profile, including significant reduction in TFEB expression. TFEB overexpression favorably modulates TAM gene expression through multiple signaling pathways. Specifically, TFEB upregulates suppressor of cytokine signaling 3 (SOCS3) and peroxisome proliferator-activated receptor γ (PPARγ) expression and autophagy/lysosome activities, inhibits NLRP3 (NLR Family Pyrin Domain Containing 3) inflammasome and hypoxia-inducible factor (HIF)-1α mediated hypoxia response, and thereby suppresses an array of effector molecules in TAMs including arginase 1, interleukin (IL)-10, IL-1β, IL-6 and prostaglandin E2. MΦ-specific TFEB deficiency promotes, while activation of TFEB using the natural disaccharide trehalose halts, breast tumor development by modulating TAMs. Analysis of human patient genome database reveals that expression levels of TFEB, SOCS3 and PPARγ are positive prognostic markers, while HIF-1α is a negative prognostic marker of breast cancer. CONCLUSIONS: Our study identifies TFEB as a master regulator of TAMs in breast cancer. TFEB controls TAM gene expression and function through multiple autophagy/lysosome-dependent and independent pathways. Therefore, pharmacological activation of TFEB would be a promising therapeutic approach to improve the efficacy of existing treatment including immune therapies for breast cancer by favorably modulating TAM function and the TME
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