Zinc-binding groups modulate selective inhibition of MMPs

The need for selective matrix metalloproteinase (MMP) inhibition is of interest because of the range of pathologies mediated by different MMP isoforms. The development of more selective MMP inhibitors (MMPi) may help to overcome some of the undesired side effects that have hindered the clinical success of these compounds. In an effort to devise new approaches to selective inhibitors, herein we describe several novel MMPi and show that their selectivity is dependent on the nature of the zinc-binding group (ZBG). This is in contrast to most current MMPi, which obtain isoform selectivity solely from the peptidomimetic backbone portion of the compound. In the present study, six different hydroxypyrone and hydroxypyridinone ZBGs were appended to a common biphenyl backbone and the inhibition efficiency of each inhibitor was determined in vitro (IC(50) values) against MMP-1, -2, -3, -7, -8, -9, -12, and -13. The results show that the selectivity profile of each inhibitor is different as a result of the various ZBGs. Computational modeling studies were used to explain some trends in the observed selectivity profiles. To assess the importance of the ZBG in a biological model, two of the semiselective, potent MMPi (and one control) were evaluated using an isolated perfused rat heart system. Hearts were subjected to ischemia reperfusion injury, and recovery of contractile function was examined. In this model, only one of the two MMPi showed significant and sustained heart recovery, demonstrating that the choice of ZBG can have a significant effect in a relevant pathophysiological endpoint.     

Effect of ageing and μ-calpain markers on meat quality from Brangus steers finished on pasture

Brangus steers (n = 247) finished on pasture were used to evaluate the effects of post-mortem ageing and polymorphism CAPN1 316 and CAPN1 4751 markers on meat tenderness and objective colour measurements (CIEL*a*b*) of m. Longissimus dorsi. Ageing meat for 7 days decreased shear force (SF) by 13.7% and improved a* (8.4%) and b* (10%) compared to ageing for 1 day. No difference between 7 and 14 days of ageing was found for SF, a* and b*. However, L* increased markedly with ageing. Fitting both markers simultaneously, CAPN1 316 showed association with SF and L* and CAPN1 4751 with a* and b*. Fitting the markers individually, CAPN1 4751 affected all traits and CAPN1 316 showed association with SF and L*. Post-mortem ageing and the use of markers represent two independent and alternative tools that could be used for improving quality of meat from Brangus cattle.     

Study of the formation of acid-based geopolymer networks and their resistance to water by time/temperature treatments

Acid-based geopolymers are known for their high temperature resistance and good mechanical performances. Some compositions also exhibit water resistance, which make them suitable for outdoor applications. This work aims to understand accurately the steps occurring during the geopolymerization process and focuses on the type of networks forming at early stages of the reaction. The sample, prepared from metakaolin and phosphoric acid, has been analyzed at different durations and temperatures during its solidification, in order to identify which compounds would crystallize. The structural characterizations have been performed using Fourier transform infrared spectroscopy and X-ray diffraction. Several Al–O–P compounds and especially AlPO₄ polymorphs crystallize in these conditions. They belong to three families of aluminophosphates and are a reliable indication of the amorphous organization of the original sample. The first one is similar to the phases that appear in the phase transition sequences of silica, the second one is composed of AlPO₄-based zeolites, and the last one is characterized by the presence of aluminum in an octahedral network. The transitions between the different phases are also discussed. Finally, the water resistance of the calcined samples is improved, and the release of acidic species in the water is limited even after a calcination at low temperature.     

Exploring the gender wage gap among project managers: A multi-national analysis of human capital and national policies

The purpose of this study was to apply human capital theory to the project management profession and associated gender wage gaps across the globe. We used salary survey data from the Project Management Institute and multi-national pay data to investigate the relationships among human capital variables, national policy, salaries, and gender wage gaps. The results showed the project management profession consistently has a narrower gender wage gap than the national gender wage gaps. Using ANOVA and mediation models, we showed that the project management gender wage gap can be reduced in the presence of national anti-discriminatory laws and national human capital development – both of which raise women's salaries to reduce the gender wage gap among project managers in Westernized countries. However, the human capital theory did not apply to the gender wage gap among project managers in Non-western contexts. Other recommendations to reduce gender wage gaps include national and organizational policies such as prohibiting discrimination against women in hiring practices, skills training, career development, and educational opportunities. We concluded there is still more work to be done to achieve equal pay between men and women, even in the project management profession and especially in Non-western contexts.     

DNA computing, sticker systems, and universality

We introduce the sticker systems, a computability model, which is an abstraction of the computations using the Watson-Crick complementarity as in Adleman's DNA computing experiment, [1]. Several types of sticker systems are shown to characterize (modulo a weak coding) the regular languages, hence the power of finite automata. One variant is proven to be equivalent to Turing machines. Another one is found to have a strictly intermediate power. Received: 10 October 1996 / 16 April 1997