Blasting is the primary comminution process in most mining operations. This process involves the highly complex and dynamic interaction between two main components. The first is the detonating explosive and the second is the rock mass into which the explosive is loaded. The mechanical properties of the rock material (such as dynamic strength, tensile strength, dynamic modulus and fracture toughness) are important considerations in understanding the blasting process. However, it is the characteristics of the geological defects (joints, foliation planes, bedding planes) within the rock mass that ultimately determine how effectively a blast performs in terms of fragmentation, all else being equal. The defect characteristics include, but are not limited to, their orientation, spacing, and mechanical properties. During the blasting process, some of the geotechnical characteristics of the rock mass are substantially changed. From the blasting outcome point of view, the most notable and important is the change in fragment size distribution that the rock mass undergoes. The pre-blast in situ defect-bounded block size distribution is transformed into the post-blast muckpile fragment size distribution. Consequently, it is fundamental to our understanding of and ability to predict the blasting process that both the blastability of a rock mass and its transformation into the fragment size distribution can be appropriately quantified.

Recent studies have demonstrated that G-protein-linked signal transduction pathways play a significant role in the developmental program of the simple eukaryotic organism Dictyostelium. We have reported previously the isolation of a G-protein beta-subunit and present here a more complete analysis of this gene. Low-stringency Southern blots and RFLP mapping studies suggest that the beta-subunit is a unique gene found on linkage group II. Its deduced amino acid sequence of 347 residues is approximately 60% identical to those of the human, Drosophila, and Caenorhabditis elegans beta-subunits. The carboxy-terminal 300 residues are about 70% identical; the amino-terminal 50 residues are quite divergent, containing only 10 identities. At all stages of growth and development, a single 1.9-kb beta-subunit mRNA is present at a high level, and a specific antibody detects a single 37-kD protein. We propose that G-protein heterotrimers are formed when this beta-subunit couples with each of the eight distinct G-protein alpha-subunits that are transiently expressed during development. Targeted disruption of the beta-subunit gene had no effect on the viability of haploid cells, but resulted in the inability of cells to aggregate.

The ITI implant system has a background of research and development of over 15 years. It is distinctive in that the implant fixtures are transmucosal from the time of placement, requiring only a single stage in surgical treatment. In a relatively simplified approach to prosthetic management, standard overdenture components and conventional fixed partial denture techniques are used. In this report the assessment, surgical treatment and post-operative management of patients using ITI Bonefit implants are described and early results from 168 consecutive fixtures placed over a period of 3 years indicated.

The principles of the laboratory procedures for making overdentures retained by bar abutments on ITI implant fixtures are described, and details of producing the master casts, making a soldered bar, and processing a prosthesis incorporating a cobalt-chromium alloy strengthener are given.

This chapter describes reversible phosphorylation of G-protein-coupled receptors controls camp oscillations in dictyostelium. Dictyostelium discoideum live as single amoebae that seek out and phagocytize bacteria. The bacteria are located by chemotaxis to secreted metabolites such as folic acid. Upon exhaustion of the food supply, growth ceases and a developmental program is initiated. When the cAMP stimulus is removed, the receptor is dephosphorylated at a rate that is independent of the level of phosphorylation. Dephosphorylation is also a biphasic event. A rapid decrease in radioactivity occurs over 3 min, initially being detected by 30 s, and the remainder gradually declines over 10 min. The half-time for maximal dephosphorylation is 2 min. When the receptor is held in the D form by cAMP, phosphate turnover on the receptor occurs at about one-fifth the initial stimulus-induced rate.

G-protein-linked cAMP receptors play an essential role in Dictyostelium development. The cAMP receptors are proposed to have seven transmembrane domains and a cytoplasmic C-terminal region. Overexpression of the receptor in cells, when the endogenous receptor is not present, results in a 10- to 50-fold increase in cAMP-binding sites. Antisense cell lines, which lack cAMP receptors, do not enter the developmental program. Ligand-induced phosphorylation is proposed to occur on serine and threonine residues in the receptor C-terminus. The kinetics of receptor phosphorylation and dephosphorylation correlate closely with the shift of receptor mobility and the adaptation of several cAMP-induced responses. Two alpha-subunits, G-alpha-1 and G-alpha-2, have been cloned and specific antisera developed against each. Both subunits are expressed as multiple RNAs with different developmental time courses. The mutant Frigid A has a functional defect in G-alpha-2 which prevents it from entering development. We propose that G-protein-linked receptor systems will be a major component in the development of many organisms.

Development in Dictyostelium results in the production of a multicellular aggregate. Aggregation depends on chemotaxis to cAMP and cell-to-cell relay of cAMP signalling. The cAMP signalling response involves surface receptor-mediated GTP-dependent activation of adenylate cyclase. Studies of the mutant synag 7 indicate that a soluble protein may be involved in this activation. Wild-type supernatants are required to restore GTP-dependent adenylate cyclase activity to mutant lysates. The surface cAMP receptor which initiates this response and is implicated in chemotaxis has been purified and an antiserum raised. The receptor undergoes a ligand-induced mobility change, probably due to serine phosphorylation, when analyzed by SDS-PAGE. Modulation of this transition is correlated with adaptation of the cells. Analysis of cells at various stages of development indicate that the receptor is most rapidly synthesized in the preaggregation stage. The antiserum was used to clone the cDNA for the receptor. Clones that have been sequenced account for about 33 000 D of the 37 000 D receptor. Hydropathy plots reveal 3 (or 4) potential membrane spanning domains; unsequenced regions are large enough to encode an additional 4 membrane spanning regions. Comparison to bovine rhodopsin reveals homology in those regions elucidated so far. Thirteen potential phosphorylation sites are present in the cytoplasmic domain and may be involved in ligand-induced phosphorylation.

Transmembrane signaling is vital to the development of the cellular slime mold Dictyostelium. Starvation initiates a developmental program in which single cells spontaneously form a multicellular structure composed of two cell types. The aggregation of these single cells is organized by extracellular cAMP. Aggregation centers form that produce waves of cAMP at precisely timed intervals. The cAMP binds to a surface receptor triggering cAMP production and secretion, which propagates the wave throughout the population. cAMP binding also triggers a number of biochemical responses associated with chemotaxis, such as guanylate cyclase activation and myosin phosphorylation. The cAMP gradient that orients the cells toward the aggregation center is established as the leading edge of the wave approaches the cell. The cells move up the concentration gradient for several minutes until the signaling and chemotactic responses adapt (spontaneously return to basal levels). Extracellular phosphodiesterase then degrades the remaining cAMP, which prepares the cells...

A total of 795 382 infants born in north London was screened for phenylketonuria using the Guthrie test between October 1969 and December 1978. During this period it became recognised that phenylketonuria is not a single disease entity but one that encompasses a number of disorders of differing clinical and biochemical severity. The overall incidence of persistent hyperphenylalaninaemia was of the order of 7 per 100 000 births (or 1 in 15 000) and all the early treated patients made normal developmental progress. During the study there was an appreciable fall in the incidence of uncomplicated transient hyperphenylalaninaemia with or without tyrosinaemia. This reduction coincided with the change in infant feeding practice in the UK which led to lower intakes of protein and phenylalanine. It was concluded that any infant found to have a persistent blood phenylalanine concentration of 240 mumol/1 (4 mg/100 ml) or greater should be followed closely.

A pilot screening programme for congenital hypothyroidism covering most of North London, Essex, Bedfordshire, and Hertfordshire entailed carrying out an assay of thyroid-stimulating hormone on single Guthrie dried blood spots. During one year 87 444 babies were screened and 26 cases of primary congenital hypothyroidism detected, giving an incidence of 1:3363. Only two cases (7.7%) had already been diagnosed on clinical grounds before the results of screening became available. In two other babies the diagnosis was delayed. The programme thus resulted in the early treatment of 22 babies, eight of whom already had pronounced features of hypothyroidism that had not been detected on routine clinical examinations. Although definitive evidence will not be available for some years, the results suggest that the prognosis for most of these babies is likely to be improved by early diagnosis; thus the introduction of national screening should be delayed no longer.

The Guthrie test was used to measure blood methionine concentrations in 670 764 neonates during the period from May 1970 to December 1977. Raised values (greater than 4 mg/100 ml; 268 mumol/l) were found in 147 babies (6--14 days old) and 55 of these still had raised values when retested 2--6 weeks later. 48 infants had transient hypermethioninaemia of at least 3 weeks' duration, one had a more persistent form associated with abnormal liver function tests, 3 had different forms of homocystinuria, and one infant, who was asymptomatic at the time of detection, had hypermethioninaemia associated with a rapidly fatal form of tyrosinamiea (tyrosinosis). Two infants could not be followed up. Transient hypermethioninaemia has not been detected in this laboratory since 1975. There was a greatly reduced incidence of transient hypermethioninaemia in girls after 1972 and in boys after 1975; this may have been due to recent changes in infant practices in the UK. Homocystinuria was last detected in this laboratory in 1972; the apparent change in incidence is significant (P less than 0.05) and suggests that the diagnostic value of this screening procedure should be reassessed.