Ensuring operational compliance and ethical responsibility in the regulation of ART: the HFEA, past, present, and future

Under the Public Bodies Bill 2010, the HFEA, cornerstone in the regulation of assisted reproduction technologies (ART) for the last twenty years, is due to be abolished. This implies that there is no longer a need for a dedicated regulator for ART and that the existing roles of the Authority as both operational compliance monitor, and instance of ethical evaluation, may be absorbed by existing healthcare regulators. This article presents a timely analysis of these disparate functions of the HFEA, charting reforms adopted in 2008 and assessing the impact of the current proposals. Taking assisted conception treatment as the focus activity, it will be shown that the last few years have seen a concentration on the HFEA as a technical regulator based upon the principles of Better Regulation, with little analysis of how the ethical responsibility of the Authority fits into this framework. The current proposal to abolish the HFEA continues to fail to address this crucial question. Notwithstanding the fact that the scope of the Authority's ethical role may be questioned, its abolition requires that the Government consider what alternatives exists - or need to be put in place - to provide both responsive operational regulation and a forum for ethical reflection and decision-making in an area which continues to pose regulatory challenges

Detection of faults in a high speed packaging machine using a multilayer perceptron (MLP)

In high speed manufacturing systems, continuous operation is desirable, with minimal disruption for repairs and service. An intelligent diagnostic monitoring system, designed to detect developing faults before catastrophic failure, or prior to undesirable reduction in output quality, is a good means of achieving this. Artificial neural networks have already been found to be of value in fault diagnosis of machinery. The aim here is to provide a system capable of detecting a number of faults, in order that maintenance can be scheduled in advance of sudden failure, and to reduce the necessity to replace parts at intervals based on mean time between failures. Instead, parts will need to be replaced only when necessary. Analysis of control information in the form of position error data from two servomotors is described.

Influence of curd cutting programme and stirring speed on the prediction of syneresis indices in cheese-making using NIR light backscatter

An NIR reflectance sensor, with a large field of view and a fibre-optic connection to a spectrometer for measuring light backscatter at 980 nm, was used to monitor the syneresis process online during cheese-making with the goal of predicting syneresis indices (curd moisture content, yield of whey and fat losses to whey) over a range of curd cutting programmes and stirring speeds. A series of trials were carried out in an 11 L cheese vat using recombined whole milk. A factorial experimental design consisting of three curd stirring speeds and three cutting programmes, was undertaken. Milk was coagulated under constant conditions and the casein gel was cut when the elastic modulus reached 35 Pa. Among the syneresis indices investigated, the most accurate and most parsimonious multivariate model developed was for predicting yield of whey involving three terms, namely light backscatter, milk fat content and cutting intensity (R2 = 0.83, SEy = 6.13 g/100 g), while the best simple model also predicted this syneresis index using the light backscatter alone (R2 = 0.80, SEy = 6.53 g/100 g). In this model the main predictor was the light backscatter response from the NIR light back scatter sensor. The sensor also predicted curd moisture with a similar accuracy.

Adsorption from aqueous solutions on opened carbon nanotubes: organic compounds speed up delivery of water from inside

We report the results of first systematic studies of organic adsorption from aqueous solutions onto relatively long single walled carbon nanotubes (four tubes, in initial and oxidised forms). Using molecular dynamics simulations (GROMACS package) we discuss the behaviour of tube-water as well as tube-adsorbate systems, for three different adsorbates (benzene, phenol and paracetamol).

Implementation of Parallel (p,q) Counters for High Speed Digital Multipliers

Both the (5,3) counter and (2,2,3) counter multiplication techniques are investigated for the efficiency of their operation speed and the viability of the architectures when implemented in a fast bipolar ECL technology. The implementation of the counters in series-gated ECL and threshold logic are contrasted for speed, noise immunity and complexity, and are critically compared with the fastest practical design of a full-adder. A novel circuit technique to overcome the problems of needing high fan-in input weights in threshold circuits through the use of negative weighted inputs is presented. The authors conclude that a (2,2,3) counter based array multiplier implemented in series-gated ECL should enable a significant increase in speed over conventional full adder based array multipliers.

Parallel Architectures for High Speed Multipliers

The authors compare various array multiplier architectures based on (p,q) counter circuits. The tradeoff in multiplier design is always between adding complexity and increasing speed. It is shown that by using a (2,2,3) counter cell it is possible to gain a significant increase in speed over a conventional full-adder, carry-save array based approach. The increase in complexity should be easily accommodated using modern emitter-coupled-logic processes.

Predicting the arrival of high-speed solar wind streams at Earth using the STEREO Heliospheric Imagers

High-speed solar wind streams modify the Earth's geomagnetic environment, perturbing the ionosphere, modulating the flux of cosmic rays into the Earth atmosphere, and triggering substorms. Such activity can affect modern technological systems. To investigate the potential for predicting the arrival of such streams at Earth, images taken by the Heliospheric Imager (HI) on the STEREO-A spacecraft have been used to identify the onsets of high-speed solar wind streams from observations of regions of increased plasma concentrations associated with corotating interaction regions, or CIRs. In order to confirm that these transients were indeed associated with CIRs and to study their average properties, arrival times predicted from the HI images were used in a superposed epoch analysis to confirm their identity in near-Earth solar wind data obtained by the Advanced Composition Explorer (ACE) spacecraft and to observe their influence on a number of salient geophysical parameters. The results are almost identical to those of a parallel superposed epoch analysis that used the onset times of the high-speed streams derived from east/west deflections in the ACE measurements of solar wind speed to predict the arrival of such streams at Earth, assuming they corotated with the Sun with a period of 27 days. Repeating the superposed epoch analysis using restricted data sets demonstrates that this technique can provide a timely prediction of the arrival of CIRs at least 1 day ahead of their arrival at Earth and that such advanced warning can be provided from a spacecraft placed 40° ahead of Earth in its orbit.

Age related changes in speed and mechanism of adult skeletal muscle stem cell migration

Skeletal muscle undergoes a progressive age-related loss in mass and function. Preservation of muscle mass depends in part on satellite cells, the resident stem cells of skeletal muscle. Reduced satellite cell function may contribute to the age-associated decrease in muscle mass. Here we focused on characterising the effect of age on satellite cell migration. We report that aged satellite cells migrate at less than half the speed of young cells. In addition, aged cells show abnormal membrane extension and retraction characteristics required for amoeboid based cell migration. Aged satellite cells displayed low levels of integrin expression. By deploying a mathematical model approach to investigate mechanism of migration, we have found that young satellite cells move in a random ‘memoryless’ manner whereas old cells demonstrate superdiffusive tendencies. Most importantly, we show that nitric oxide, a key regulator of cell migration, reversed the loss in migration speed and reinstated the unbiased mechanism of movement in aged satellite cells. Finally we found that although Hepatocyte Growth Factor increased the rate of aged satellite cell movement it did not restore the memoryless migration characteristics displayed in young cells. Our study shows that satellite cell migration, a key component of skeletal muscle regeneration, is compromised during aging. However, we propose clinically approved drugs could be used to overcome these detrimental changes.

Large is fast, small is tight: determinants of speed and affinity in subunit capture by a periplasmic chaperone

The chaperone/usher pathway assembles surface virulence organelles of Gram-negative bacteria, consisting of fibers of linearly polymerized protein subunits. Fiber subunits are connected through 'donor strand complementation': each subunit completes the immunoglobulin (Ig)-like fold of the neighboring subunit by donating the seventh β-strand in trans. Whereas the folding of Ig domains is a fast first-order process, folding of Ig modules into the fiber conformation is a slow second-order process. Periplasmic chaperones separate this process in two parts by forming transient complexes with subunits. Interactions between chaperones and subunits are also based on the principle of donor strand complementation. In this study, we have performed mutagenesis of the binding motifs of the Caf1M chaperone and Caf1 capsular subunit from Yersinia pestis and analyzed the effect of the mutations on the structure, stability, and kinetics of Caf1M-Caf1 and Caf1-Caf1 interactions. The results suggest that a large hydrophobic effect combined with extensive main-chain hydrogen bonding enables Caf1M to rapidly bind an early folding intermediate of Caf1 and direct its partial folding. The switch from the Caf1M-Caf1 contact to the less hydrophobic, but considerably tighter and less dynamic Caf1-Caf1 contact occurs via the zip-out-zip-in donor strand exchange pathway with pocket 5 acting as the initiation site. Based on these findings, Caf1M was engineered to bind Caf1 faster, tighter, or both faster and tighter. To our knowledge, this is the first successful attempt to rationally design an assembly chaperone with improved chaperone function.