The evolution of multiple active site configurations in a designed enzyme

Developments in computational chemistry, bioinformatics, and laboratory evolution have facilitated the de novo design and catalytic optimization of enzymes. Besides creating useful catalysts, the generation and iterative improvement of designed enzymes can provide valuable insight into the interplay between the many phenomena that have been suggested to contribute to catalysis. In this work, we follow changes in conformational sampling, electrostatic preorganization, and quantum tunneling along the evolutionary trajectory of a designed Kemp eliminase. We observe that in the Kemp Eliminase KE07, instability of the designed active site leads to the emergence of two additional active site configurations. Evolutionary conformational selection then gradually stabilizes the most efficient configuration, leading to an improved enzyme. This work exemplifies the link between conformational plasticity and evolvability and demonstrates that residues remote from the active sites of enzymes play crucial roles in controlling and shaping the active site for efficient catalysis

Measurement of D+- and D0 production in deep inelastic scattering using a lifetime tag at HERA

The production of D-+/-- and D-0-mesons has been measured with the ZEUS detector at HERA using an integrated luminosity of 133.6 pb(-1). The measurements cover the kinematic range 5 < Q(2) < 1000 GeV2, 0.02 < y < 0.7, 1.5 < p(T)(D) < 15 GeV and |eta(D)| < 1.6. Combinatorial background to the D-meson signals is reduced by using the ZEUS microvertex detector to reconstruct displaced secondary vertices. Production cross sections are compared with the predictions of next-to-leading-order QCD, which is found to describe the data well. Measurements are extrapolated to the full kinematic phase space in order to obtain the open-charm contribution, F-2(c (c) over bar), to the proton structure function, F-2

Attrition and bias in the MRC cognitive function and ageing study: an epidemiological investigation

BACKGROUND: Any hypothesis in longitudinal studies may be affected by attrition and poor response rates. The MRC Cognitive Function and Ageing study (MRC CFAS) is a population based longitudinal study in five centres with identical methodology in England and Wales each recruiting approximately 2,500 individuals. This paper aims to identify potential biases in the two-year follow-up interviews. METHODS: Initial non-response: Those not in the baseline interviews were compared in terms of mortality to those who were in the baseline interviews at the time of the second wave interviews (1993–1996). Longitudinal attrition: Logistic regression analysis was used to examine baseline differences between individuals who took part in the two-year longitudinal wave compared with those who did not. RESULTS: Initial non-response: Individuals who moved away after sampling but before baseline interview were 1.8 times more likely to die by two years (95% Confidence interval(CI) 1.3–2.4) compared to respondents, after adjusting for age. The refusers had a slightly higher, but similar mortality pattern to responders (Odds ratio 1.2, 95%CI 1.1–1.4). Longitudinal attrition: Predictors for drop out due to death were being older, male, having impaired activities of daily living, poor self-perceived health, poor cognitive ability and smoking. Similarly individuals who refused were more likely to have poor cognitive ability, but had less years of full-time education and were more often living in their own home though less likely to be living alone. There was a higher refusal rate in the rural centres. Individuals who moved away or were uncontactable were more likely to be single, smokers, demented or depressed and were less likely to have moved if in warden-controlled accommodation at baseline. CONCLUSIONS: Longitudinal estimation of factors mentioned above could be biased, particularly cognitive ability and estimates of movements from own home to residential homes. However, these differences could also affect other investigations, particularly the estimates of incidence and longitudinal effects of health and psychiatric diseases, where the factors shown here to be associated with attrition are risk factors for the diseases. All longitudinal studies should investigate attrition and this may help with aspects of design and with the analysis of specific hypotheses

Effects of polarization field on formation of two-dimensional electron gas in (0001) and (11(2)over-bar0) plane AlGaN/GaN heterostructures

Photoluminescence (PL) and temperature-dependent Hall effect measurements were carried out in (0001) and (11 (2) over bar0) AlGaN/GaN heterostructures grown on sapphire substrates by metalorganic chemical vapor deposition. There are strong spontaneous and piezoelectric electric fields (SPF) along the growth orientation of the (0001) AlGaN/GaN heterostructures. At the same time there are no corresponding SPF along that of the (1120) AlGaN/GaN. A strong PL peak related to the recombination between two-dimensional electron gas (2DEG) and photoexcited holes was observed at 3.258 eV at room temperature in (0001) AlGaN/GaN heterointerfaces while no corresponding PL peak was observed in (11 (2) over bar0). The existence of a 2DEG was observed in (0001) AlGaN/GaN multi-layers with a mobility saturated at 6000 cm(2)/V s below 80 K, whereas a much lower mobility was measured in (11 (2) over bar0). These results indicated that the SPF was the main element to cause the high mobility and high sheet-electron-density 2DEG in AlGaN/GaN heterostructures. (C) 2004 Elsevier B.V. All rights reserved

Effects of polarization field on formation of two-dimensional electron gas in (0001) and (11(2)over-bar0) plane AlGaN/GaN heterostructures

Photoluminescence (PL) and temperature-dependent Hall effect measurements were carried out in (0001) and (11 (2) over bar0) AlGaN/GaN heterostructures grown on sapphire substrates by metalorganic chemical vapor deposition. There are strong spontaneous and piezoelectric electric fields (SPF) along the growth orientation of the (0001) AlGaN/GaN heterostructures. At the same time there are no corresponding SPF along that of the (1120) AlGaN/GaN. A strong PL peak related to the recombination between two-dimensional electron gas (2DEG) and photoexcited holes was observed at 3.258 eV at room temperature in (0001) AlGaN/GaN heterointerfaces while no corresponding PL peak was observed in (11 (2) over bar0). The existence of a 2DEG was observed in (0001) AlGaN/GaN multi-layers with a mobility saturated at 6000 cm(2)/V s below 80 K, whereas a much lower mobility was measured in (11 (2) over bar0). These results indicated that the SPF was the main element to cause the high mobility and high sheet-electron-density 2DEG in AlGaN/GaN heterostructures. (C) 2004 Elsevier B.V. All rights reserved