Identification and synthesis of altered peptides modulating T cell recognition of a synthetic peptide antigen

In studies of T cell responses to synthetic peptides we have observed agonist and antagonist activities associated with contaminants identified within the parent synthesis. The synthesis of two candidate analogues implied by a peptide contaminant formed during the synthesis of La 51-58 (IMIKFNRL) has been carried out. The peptide contaminant was 17-18 Da smaller than the parent peptide consistent with a modified asparagine residue at position 6 and so we synthesised both an aspartimide and a nitrile analogue, representing cyclisation or dehydration of the asparagine residue. The candidate aspartimide and nitrile analogues both bound empty MHC class I molecules to form allo determinants recognised by monoclonal antibodies. These results demonstrate that altered synthetic peptides can bind class I MHC molecules and prompt caution in the use of synthetic peptides as a source of immunising antigen.     

Discrepancies in normative data between Lunar and Hologic DXA systems

Many studies have shown the high correlation between Lunar and Hologic DXA bone mineral density (BMD) measurements despite differences in absolute calibration. However, in clinical practice, raw BMD values (in g/cm2) are not normally used for assessing skeletal status and fracture risk. Instead, the BMD values are expressed in terms of the number of standard deviations above or below the young normal value (commonly referred to as the T-score). If the normative populations of the various systems are consistent, the standard deviation scores should also be consistent. For this reason, the World Health Organization (WHO) recently established diagnostic criteria for osteoporosis based on T-scores and not BMD. However, few studies have compared the instruments in terms of their standard deviation scores. In this study, we used linear regression to compare T-scores in 83 women at L1-4 and 120 women at the femoral neck obtained on a Lunar DPX and a Hologic QDR-1000/W system. patient BMD and T-score measurements were highly correlated between the two systems (r > 0.95). No clinically significant difference in L1-4 T-scores was seen (less than 0.1 SD). However, linear regression analysis confirmed a systematic difference of 0.9 SD between the femoral neck T-scores. This discrepancy is caused by: (1) differences in the normal populations, and (2) differences in statistical models used to determine the young normal mean and standard deviation. In an attempt to correct the discrepancy, the female young normal mean and standard deviation were recalculated for the femoral neck using published epidemiological data from NHANES and existing DXA cross-calibration equations. The Hologic young normal value (mean +/- SD) was redefined as 0.85 +/- 0.11 g/cm2, while the Lunar value was redefined as 1.00 +/- 0.11 g/cm2. When the femoral neck T-scores for the study population were recalculated on the basis of these new values, the results were equivalent between manufactures, effectively eliminating the discrepancy. However, the revised values should be confirmed by additional measurements in young normal adults.     

Glycine conjugation of para-aminobenzoic acid (PABA): a quantitative test of liver function

N-Acetyl aspartate (NAA) is the second most abundant amino acid in the human brain. NAA is synthesized by L-aspartate N-acetyl transferase or by cleavage from N-acetyl aspartyl glutamate by N-acylated alpha-linked L-amino dipeptidase (NAALADase); and it is catabolized to acetate and aspartate by N-acetyl aspartate amino hydrolase (amino acylase II). NAA is localized primarily to neurons, where it is concentrated in the cytosol. Although NAA is devoid of neurophysiological effects, it serves as an acetyl donor, an initiator of protein synthesis or a carbon transfer source across the mitochondrial membrane. The concentration of NAA in human brain increases 3-fold between midgestation and adulthood. In Canavan's Disease, an autosomal recessive disorder due to a null mutation in amino acylase II, NAA levels in brain are markedly increased and disrupt myelination. NAA levels have been found to be reduced in neurodegenerative disorders, including Alzheimer's Disease and Huntington's Disease. Since endogenous NAA can be readily detected in human brain by magnetic resonance spectroscopy, it is increasingly being exploited as a marker for functional and structural integrity of neurons in an expanding number of disorders.     

Spectrum analysis of ionospheric radar returns

A digital method of extracting ionospheric information from the Doppler broadening of radar signals is presented. 1 bit correlation, used by Weinreb in radioastronomy, is applied to measuring autocorrelation functions of ionospheric incoherent scatter returns. Calculated correlation functions are fitted to the observations to derive electron and ion temperatures.     

A computer program for the minimal realization of transfer function matrices

A computer program for finding the minimal realizations of transfer function matrices is described. An example is included to illustrate the procedure.     

Aggregation of the UK's energy conservation options

Should the UK economy grow at an annual rate of $\text{2}\text{1}\text{2}$ to 3 per cent between now and the end of the century, total primary demand for energy might reach about 600 mtce if the nation paid no serious attention to energy conservation. However, the adoption of a rigorous, technology based conservation programme as described in this paper could mean that primary energy demand would be only between 400 and 450 mtce.The main options for saving energy by the application of technology are seen to be as follows, in ranking order: economies in general industrial operations insulation of buildings improvements in the mpg of motor vehicles economies in the production of chemicals economies in the production of steel products widespread introduction of heat pumps combined heat and power/district heatingThe magnitude of the potential savings corresponds to a savings on the national fuel bill, if prices doubled, of nearly £8000 millions a year by the end of the century. The integrated savings over the intervening years could reach £40,000 millions with present-day prices.The reduced rate of growth of energy demand due to pursuing a rigorous energy conservation programme could mean that annual primary demand in the year 2000 would be equal to what it would have been 12 years earlier in the absence of conservation. This ‘buying’ of time could be valuable in terms of developing new energy supply technologies.If the package of conservation measures as described in this paper were actually carried out, a major shift of resources away from the energy supply industries into general manufacturing industry would necessarily occur.Although the pursuance of an all-out energy conservation programme based on appropriate technologies would appear highly desirable, it is unlikely to occur if left to market forces, for various reasons. Government would need to play a conspicuous role in both starting such a programme and in maintaining its momentum over many years.     

Reducing the effect of charge-transfer inefficiency in a c.c.d. video integrator

The usefulness of c.c.d.s as video integrators is limited by the charge-transfer inefficiency of the device. A method of coding the signal before passage through the c.c.d. is described which greatly reduces the effect of this inefficiency.