113 research outputs found
Reevaluation of the Impact of Coal Mining on the Virginia State Budge
Downstream Strategies, an environmental consulting and policy analysis firm, published The Impact of Coal on the Virginia State Budget in 2012, finding that the coal mining industry was responsible for a net cost of 21.9 million USD to the Commonwealth in 2009 (considering only the Virginia General Assembly's General Fund and Transportation Fund revenues and expenditures). We provide a reanalysis of the same topic, considering the effect the presence of the coal industry has on the entire state budget that is not limited to the General Fund. We estimate that in our study year of 2011, the coal industry contributed 31.95 million USD in taxes and fees to the state while the Commonwealth's expenditures relating to the coal industry totaled 24.4 million USD. However, firms producing coal in Virginia also benefit from two exclusive refundable tax credits which we estimate combine to 49.37 million USD. We find that the coal industry was associated with a net cost of 36.7 million USD to the Virginia state budget in 2011
An evaluation of whether the management practices of four companies (representing the printing industry in Bulawayo, Zimbabwe) have affected their profitability and success in the period 2003-2004
Nohria, Joyce and Roberson, a trio of academics in the United States, wrote an article in the July issue of the Harvard Business Review in 2003 entitled "What Really Works". For several years they had studied the management practices of 160 companies in the United States with a view to determining what made certain companies consistently successful. They found that the most profitable companies in their study were not successful because they utilised the latest management tools and techniques, but rather that they had a strong grasp of business basics. Companies outperformed their industrial peers, because they excelled at what they called the four primary management practices - Strategy, Execution, Culture and Structure. These practices were supplemented by a proficiency in any two out of four secondary practices - Talent, Innovation, Leadership and Mergers and Partnerships. They called this winning combination the 4 + 2 Formula for business success. The purpose of this thesis is to determine whether competence in these management practices applies in the Third World. The study will concentrate on four companies representing the printing industry in Bulawayo, Zimbabwe. Zimbabwean companies are faced with a number of unusual obstacles that do not exist in First World free market economies. This study will attempt to examine the nature of the obstacles faced and how each company deals with them. It will determine whether the management practices outlined by Nohria et ai, are valued to the same degree in the Zimbabwean context, and how far they contribute to profitability.Because of the pace of change in Zimbabwe, the research will focus on the period 2003 - 2004 and evaluate another management practice - change management. The forces of change can often be so radically negative, that if companies are not adequately prepared, they may face imminent collapse. Change management, the process of anticipating, reacting to and driving forces of change, has become a vital competency. Without it, the prospects of profitability and success in the Zimbabwean environment are slim. For this reason, this management practice will be given the same focus as those eight discussed by Nohria et al
An Analysis of Folic Acid Supplementation in Women Presenting For Antenatal Care
Background: Neural tube defects (NTDs) are major congenital malformations that are potentially preventable if the woman takes periconceptional folic acid (FA) supplements. A recent report found that NTD incidence had increased in Ireland. This study examined the usage of FA supplementation in women presenting for antenatal care in a maternity hospital
Duration of Periconceptual Folic Acid Supplementation in Women Booking for Antenatal Care
Objective: To provide accurate estimates of the commencement time, duration and dosage of folic acid (FA) supplementation taken by Irish women in the periconceptional period. The study also aimed to establish the factors associated with optimal FA supplementation practices. Design: Cross-sectional observational study. Women’s clinical and sociodemographic details were computerised. Maternal weight and height were measured before calculating BMI. Detailed FA supplementation questionnaires were completed under the supervision of a trained researcher. Setting: A large university maternity hospital, Republic of Ireland, January 2014–April 2016. Subjects: Women (n 856) recruited at their convenience in the first trimester. Results: While almost all of the women (97 %) were taking FA at enrolment, only one in four women took FA for at least 12 weeks preconceptionally (n 208). Among the 44% of women who were supplementing with FA preconceptionally, 44% (162/370) reported taking FA for less than the 12 weeks required to achieve optimal red-blood-cell folate levels for prevention of neural tube defects. On multivariate analysis, only planned pregnancy and nulliparity were associated with taking FA for at least 12 weeks preconceptionally. Among women who only took FA postconceptionally, almost two-thirds commenced it after day 28 of their pregnancy when the neural tube had already closed. Conclusions: As the timing of FA was suboptimal both before and after conception, we recommend that current national FA guidelines need to be reviewed
Coal Mining, Economic Development, and the Natural Resource Curse
Coal mining has a long legacy of providing needed jobs in isolated communities but it is also associated with places that suffer from high poverty and weaker long-term economic growth. Yet, the industry has greatly changed in recent decades. Regulations, first on air, have altered the geography of coal mining, pushing it west from Appalachia. Likewise, technological change has reduced labor demand and has led to relatively new mining practices such as invasive mountain-top approaches. Thus, the economic footprint of coal mining has greatly changed in an era when the industry appears to be on the decline. This study investigates whether these changes along with coal’s “boom/bust” cycles have affected economic prosperity in coal country. We separately examine the Appalachian region from the rest of the U.S. due to Appalachia’s unique history and different mining practices. Our study takes a new look at the industry by assessing the winners and losers of coal development around a range of economic indicators and addressing whether the natural resources curse applies to contemporary American coal communities today. The results suggest that modern coal mining has rather nuanced effects that differ between Appalachia and the rest of the U.S. We do not find strong evidence of a resources curse, except that coal mining has a consistent inverse association with measures linked to population growth and entrepreneurship, and thereby future economic growth
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Rational optimization of tolC as a powerful dual selectable marker for genome engineering
Selection has been invaluable for genetic manipulation, although counter-selection has historically exhibited limited robustness and convenience. TolC, an outer membrane pore involved in transmembrane transport in E. coli, has been implemented as a selectable/counter-selectable marker, but counter-selection escape frequency using colicin E1 precludes using tolC for inefficient genetic manipulations and/or with large libraries. Here, we leveraged unbiased deep sequencing of 96 independent lineages exhibiting counter-selection escape to identify loss-of-function mutations, which offered mechanistic insight and guided strain engineering to reduce counter-selection escape frequency by ∼40-fold. We fundamentally improved the tolC counter-selection by supplementing a second agent, vancomycin, which reduces counter-selection escape by 425-fold, compared colicin E1 alone. Combining these improvements in a mismatch repair proficient strain reduced counter-selection escape frequency by 1.3E6-fold in total, making tolC counter-selection as effective as most selectable markers, and adding a valuable tool to the genome editing toolbox. These improvements permitted us to perform stable and continuous rounds of selection/counter-selection using tolC, enabling replacement of 10 alleles without requiring genotypic screening for the first time. Finally, we combined these advances to create an optimized E. coli strain for genome engineering that is ∼10-fold more efficient at achieving allelic diversity than previous best practices
The Impact of Peripheral Venous Catheter Procedural Kits on Improving Clinical Outcomes in Hospitalised Patients
Emergent rules for codon choice elucidated by editing rare arginine codons in Escherichia coli
The degeneracy of the genetic code allows nucleic acids to encode amino acid identity as well as noncoding information for gene regulation and genome maintenance. The rare arginine codons AGA and AGG (AGR) present a case study in codon choice, with AGRs encoding important transcriptional and translational properties distinct from the other synonymous alternatives (CGN). We created a strain of Escherichia coli with all 123 instances of AGR codons removed from all essential genes. We readily replaced 110 AGR codons with the synonymous CGU codons, but the remaining 13 “recalcitrant” AGRs required diversification to identify viable alternatives. Successful replacement codons tended to conserve local ribosomal binding site-like motifs and local mRNA secondary structure, sometimes at the expense of amino acid identity. Based on these observations, we empirically defined metrics for a multidimensional “safe replacement zone” (SRZ) within which alternative codons are more likely to be viable. To evaluate synonymous and nonsynonymous alternatives to essential AGRs further, we implemented a CRISPR/Cas9-based method to deplete a diversified population of a wild-type allele, allowing us to evaluate exhaustively the fitness impact of all 64 codon alternatives. Using this method, we confirmed the relevance of the SRZ by tracking codon fitness over time in 14 different genes, finding that codons that fall outside the SRZ are rapidly depleted from a growing population. Our unbiased and systematic strategy for identifying unpredicted design flaws in synthetic genomes and for elucidating rules governing codon choice will be crucial for designing genomes exhibiting radically altered genetic codes.United States. Department of Energy (DE-FG02-02ER63445
Revealing the Mechanism for Covalent Inhibition of Glycoside Hydrolases by Carbasugars at an Atomic Level
Mechanism-based glycoside hydrolase inhibitors are carbohydrate analogs that mimic the natural substrate’s structure. Their covalent bond formation with the glycoside hydrolase makes these compounds excellent tools for chemical biology and potential drug candidates. Here we report the synthesis of cyclohexene-based α-galactopyranoside mimics and the kinetic and structural characterization of their inhibitory activity toward an α-galactosidase from Thermotoga maritima (TmGalA). By solving the structures of several enzyme-bound species during mechanism-based covalent inhibition of TmGalA, we show that the Michaelis complexes for intact inhibitor and product have half-chair (2H3) conformations for the cyclohexene fragment, while the covalently linked intermediate adopts a flattened half-chair (2H3) conformation. Hybrid QM/MM calculations confirm the structural and electronic properties of the enzyme-bound species and provide insight into key interactions in the enzyme-active site. These insights should stimulate the design of mechanism-based glycoside hydrolase inhibitors with tailored chemical properties
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