91 research outputs found

    The development of absorptive capacity-based innovation in a construction SME

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    Traditionally, construction has been a transaction-oriented industry. However, it is changing from the design-bid-build process into a business based on innovation capability and performance management, in which contracts are awarded on the basis of factors such as knowledge, intellectual capital and skills. This change presents a challenge to construction-sector SMEs with scarce resources, which must find ways to innovate based on those attributes to ensure their future competitiveness. This paper explores how dynamic capability, using an absorptive capacity framework in response to these challenges, has been developed in a construction-based SME. The paper also contributes to the literature on absorptive capacity and innovation by showing how the construct can be operationalized within an organization. The company studied formed a Knowledge Transfer Partnership using action research over a two-year period with a local university. The aim was to increase its absorptive capacity and hence its ability to meet the changing market challenges. The findings show that absorptive capacity can be operationalized into a change management approach for improving capability-based competitiveness. Moreover, it is important for absorptive capacity constructs and language to be contextualized within a given organizational setting (as in the case of the construction-based SME in the present study)

    In-Season Hip Thrust vs. Back Squat Training in Female High School Soccer Players

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    International Journal of Exercise Science 13(4): 49-61, 2020. The barbell back squat provides a highly effective training stimulus to improve lower body strength, speed, and power, which are considered key components of athletic performance in many sports. The barbell hip thrust exercise utilizes similar musculature, and is popular among practitioners, but has received far less scientific examination. The purpose of this study was to evaluate the effects of an in-season resistance training program with hip thrusts or back squats on physical performance in adolescent female soccer players. Fourteen players completed identical whole-body resistance training twice per week for 6 weeks, except one group used the barbell hip thrust (HT) (n = 6) and the other the back squat (SQ) (n = 8). Improvements were observed for both groups in hip thrust 3RM (HT = 34.0%, SQ = 23.8%), back squat 3RM (HT = 34.6%, SQ = 31.0%), vertical jump (HT = 5.4%, SQ = 4.9%), broad jump (HT = 10.5%, SQ = 8.1%), ball kicking distance (HT = 13.2%, SQ = 8.1%), and pro-agility (HT = -1.5%, SQ = -1.5%; faster), but not 36.6-m dash (HT = 2.9%, SQ = 1.9%; slower) with no significant between-group differences. These data indicate that both the hip thrust and the squat provide an effective stimulus to improve these sport-specific performance measures. Practitioners should consider these findings in combination with other factors (equipment availability, ability to coach the movement, training goals, injuries, etc.) when selecting exercises

    Tautomer-Specific Deacylation and Ī©-Loop Flexibility Explain the Carbapenem-Hydrolyzing Broad-Spectrum Activity of the KPC-2 Ī²-Lactamase

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    KPC-2 (Klebsiella pneumoniae carbapenemase-2) is a globally disseminated serine-Ī²-lactamase (SBL) responsible for extensive Ī²-lactam antibiotic resistance in Gram-negative pathogens. SBLs inactivate Ī²-lactams via a mechanism involving a hydrolytically labile covalent acyl-enzyme intermediate. Carbapenems, the most potent Ī²-lactams, evade the activity of many SBLs by forming long-lived inhibitory acyl-enzymes; however, carbapenemases such as KPC-2 efficiently deacylate carbapenem acyl-enzymes. We present high-resolution (1.25ā€“1.4 ƅ) crystal structures of KPC-2 acyl-enzymes with representative penicillins (ampicillin), cephalosporins (cefalothin), and carbapenems (imipenem, meropenem, and ertapenem) obtained utilizing an isosteric deacylation-deficient mutant (E166Q). The mobility of the Ī©-loop (residues 165ā€“170) negatively correlates with antibiotic turnover rates (kcat), highlighting the role of this region in positioning catalytic residues for efficient hydrolysis of different Ī²-lactams. Carbapenem-derived acyl-enzyme structures reveal the predominance of the Ī”1-(2R) imine rather than the Ī”2 enamine tautomer. Quantum mechanics/molecular mechanics molecular dynamics simulations of KPC-2:meropenem acyl-enzyme deacylation used an adaptive string method to differentiate the reactivity of the two isomers. These identify the Ī”1-(2R) isomer as having a significantly (7 kcal/mol) higher barrier than the Ī”2 tautomer for the (rate-determining) formation of the tetrahedral deacylation intermediate. Deacylation is therefore likely to proceed predominantly from the Ī”2, rather than the Ī”1-(2R) acyl-enzyme, facilitated by tautomer-specific differences in hydrogen-bonding networks involving the carbapenem C-3 carboxylate and the deacylating water and stabilization by protonated N-4, accumulating a negative charge on the Ī”2 enamine-derived oxyanion. Taken together, our data show how the flexible Ī©-loop helps confer broad-spectrum activity upon KPC-2, while carbapenemase activity stems from efficient deacylation of the Ī”2-enamine acyl-enzyme tautomer

    Interactions between amiodarone and the hERG potassium channel pore determined with mutagenesis and in silico docking

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    AbstractThe antiarrhythmic drug amiodarone delays cardiac repolarisation through inhibition of hERG-encoded potassium channels responsible for the rapid delayed rectifier potassium current (IKr). This study aimed to elucidate molecular determinants of amiodarone binding to the hERG channel. Whole-cell patch-clamp recordings were made at 37Ā°C of ionic current (IhERG) carried by wild-type (WT) or mutant hERG channels expressed in HEK293 cells. Alanine mutagenesis and ligand docking were used to investigate the roles of pore cavity amino-acid residues in amiodarone binding. Amiodarone inhibited WT outward IhERG tails with a half-maximal inhibitory concentration (IC50) of āˆ¼45nM, whilst inward IhERG tails in a high K+ external solution ([K+]e) of 94mM were blocked with an IC50 of 117.8nM. Amiodaroneā€™s inhibitory action was contingent upon channel gating. Alanine-mutagenesis identified multiple residues directly or indirectly involved in amiodarone binding. The IC50 for the S6 aromatic Y652A mutation was increased to āˆ¼20-fold that of WT IhERG, similar to the pore helical mutant S624A (āˆ¼22-fold WT control). The IC50 for F656A mutant IhERG was āˆ¼17-fold its corresponding WT control. Computational docking using a MthK-based hERG model differentiated residues likely to interact directly with drug and those whose Ala mutation may affect drug block allosterically. The requirements for amiodarone block of aromatic residues F656 and Y652 within the hERG pore cavity are smaller than for other high affinity IhERG inhibitors, with relative importance to amiodarone binding of the residues investigated being S624Aāˆ¼Y652A>F656A>V659A>G648A>T623A

    Current evidence shows no influence of women's menstrual cycle phase on acute strength performance or adaptations to resistance exercise training

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    Introduction: The bias towards excluding women from exercise science research is often due to the assumption that cyclical fluctuations in reproductive hormones influence resistance exercise performance and exercise-induced adaptations. Methods: Hence, the purpose of this umbrella review was to examine and critically evaluate the evidence from meta-analyses and systematic reviews on the influence of menstrual cycle phase on acute performance and chronic adaptations to resistance exercise training (RET). Results: We observed highly variable findings among the published reviews on the ostensible effects of female sex hormones on relevant RET-induced outcomes, including strength, exercise performance, and hypertrophy. Discussion: We highlight the importance of comprehensive menstrual cycle verification methods, as we noted a pattern of poor and inconsistent methodological practices in the literature. In our opinion, it is premature to conclude that short-term fluctuations in reproductive hormones appreciably influence acute exercise performance or longer-term strength or hypertrophic adaptations to RET

    Re-Imagining School Feeding : A High-Return Investment in Human Capital and Local Economies

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    Analysis shows that a quality education, combined with a guaranteed package of health and nutrition interventions at school, such as school feeding, can contribute to child and adolescent development and build human capital. School feeding programs can help get children into school and help them stay there, increasing enrollment and reducing absenteeism. Once children are in the classroom, these programs can contribute to their learning by avoiding hunger and enhancing cognitive abilities. The benefits are especially great for the poorest and most disadvantaged children. As highlighted in the World Bankā€™s 2018 World Development Report (World Bank 2018), countries need to prioritize learning, not just schooling. Children must be healthy, not hungry, if they are to match learning opportunities with the ability to learn. In the most vulnerable communities, nutrition-sensitive school meals can offer children a regular source of nutrients that are essential for their mental and physical development. And for the growing number of countries with a ā€œdouble burdenā€ of undernutrition and emerging obesity problems, well-designed school meals can help set children on the path toward more healthy diets. In Latin America, for example, where there is a growing burden of noncommunicable diseases (NCDs), school feeding programs are a key intervention in reducing undernutrition and promoting healthy diet choices. Mexicoā€™s experience reducing sugary beverages in school cafeterias, for example, was found to be beneficial in advancing a healthy lifestyle. A large trial of school-based interventions in China also found that nutritional or physical activity interventions alone are not as effective as a joint program that combines nutritional and educational interventions. In poor communities, economic benefits from school feeding programs are also evidentā€”reducing poverty by boosting income for households and communities as a whole. For families, the value of meals in school is equivalent to about 10 percent of a householdā€™s income. For families with several children, that can mean substantial savings. As a result, school feeding programs are often part of social safety nets in poor countries, and they can be a stable way to reliably target pro-poor investments into communities, as well as a system that can be scaled up rapidly to respond to crises. There are also direct economic benefits for smallholder farmers in the community. Buying local food creates stable markets, boosting local agriculture, impacting rural transformation, and strengthening local food systems. In Brazil, for example, 30 percent of all purchases for school feeding come from smallholder agriculture (Drake and others 2016). These farmers are oftentimes parents with schoolchildren, helping them break intergenerational cycles of hunger and poverty. Notably, benefits to households and communities offer important synergies. The economic growth in poor communities helps provide stability and better-quality education and health systems that promote human capital. At the same time, children and adolescents grow up to enjoy better employment and social opportunities as their communities grow

    Case for Diagnosis

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