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Breast cancer is second most commonly diagnosed cancer worldwide. In order to find the cure, it is necessary to quickly diagnose the disease accurately and treat it based on the kind of symptoms appeared. Breast cancer has several classifications, which may help to determine the best treatment. The most important of these classifications are binary classification, either benign or malignant. If the cancer is in benign stage, less invasive and risk of treatments is used than for malignant stage. The main cause of breast cancer is when a single cell or group of cells escapes from the usual controls, that regulate cellular growth and begins to multiply and spread. This activity may result in a mass, tumor or neoplasm. The present paper implies the edge detection techniques for the cancer cell detection purpose. The present paper deals with observation of breast cancer classification through Image Processing using the various filters which are mainly gradient based Roberts and Sobel. Laplacian based edge detector which is Canny edge detector. The various aspects and the implementation of above mentioned filters has been put across in the present paper. The images and data sample have been taken from the Digital Database for Screening Mammography (DDSM) and American cancer society and an effort has been made for the detection of malignant cells responsible for cancer

The National Institute of Health (NIH) held an innovative, first of its kind, bioengineering symposium in Bethesda, Maryland, USA on February 27 - 28, 1998 at the Natcher Conference Centre. The purpose of this meeting was to chart the future of bioengineering research into the 21st century.Harold E. Varmus, MD, Noble Laureate in Medicine and Director of NIH, welcomed the delegates during the opening session. According to Dr. Varmus, “Bioengineering advances the nation's health by increasing biological knowledge through the use of engineering principles and techniques and contributes methods that have facilitated the development of novel devices and drugs”.

Design of an artificial knee was developed using computer 3-D modeling, the high flexion knee was obtained by using a multi-radii design pattern, The increase of final 20 degrees in flexion was obtained by increasing the condylar radii of curvature. The model of the high flexion knee was developed and one of the models was subjected to finite element modeling and analysis. The compositions of components in the artificial knee were, femoral component and the tibial component were metal, whereas the patellar component and the meniscal insert were made using polyethylene. The metal component used for the analysis in this study was Ti6Al4V and the polyethylene used was UHMWPE. Overall biomaterials chosen were: meniscus (UHMWPE, mass = 0.0183701 kg, volume = 1.97518e-005 m3), tibial component (Ti6Al4V, mass = 0.0584655 kg, volume = 1.32013e-005 m3), femoral component (Ti6Al4V, mass = 0.153122 kg, volume = 3.45742e-005 m3), total artificial assembly (mass = 0.229958 kg, volume = 6.75e-005m3). However, in this design the load had been taken to 10 times the body weight. The weight over single knee is only half the maximum load as the load is shared between the two knee joints. Following were the loading conditions, taking average body weight to be 70Kgs and taking extreme loading conditions of up to 10 times the body weight, i.e. 700Kgs on each of the leg performed the Finite Element Analysis (FEA) over the newly designed knee. The loading was done at an increment of 100 Kgs. The loading conditions and the meshing details for the analysis of the assembly were Jacobian check: 4 points, element size: 0.40735 cm, tolerance: 0.20367 cm, quality: high, number of elements: 80909, number of nodes: 126898. A maximum load of 600 Kgs is optimum for this model. The other components observed linear elastic behavior for the applied loads. Based on these results it was determined that the load bearing capacity of the model were well within the failure levels of the materials used for the analysis. A maximum load of 600 Kgs is optimum for this model. The other components observed linear elastic behavior for the applied loads. Based on these results it was determined that the load bearing capacity of the model were well within the failure levels of the materials used for the analysis. Conclusion drawn from this is that for the first time an innovative new design of an artificial knee joint to suite a segment of some religious population has been developed. This allows them to pray, bend in different positions and squat without too much difficulty.

Intradiscal and intervertebral pressure transducers were developed. They were used to map the pressures in the nucleus and within the annulus of the human spinal segments. Their stressrelaxation were recorded over a period of time for nucleus pressure, applied load, and peripherial strain against time. The results show that for normal discs, pressures in the nucleus are viscoelastic in nature with the applied compressive load. Mechanical strains which develop around the periphery of the vertebral body are also viscoelastic with the applied compressive load. Applied compressive load against time also shows viscoelastic behavior. However, annulus does not respond viscoelastically with the applied load. It showed a linear response to compressive loading.

A set of intervertebral pressure transducer (IVPT) and an intradiscal pressure transducer (IDPT) were developed to measure the pressures in the nucleus pulposus and around the annulus. Human lumbar spinal segments were loaded up to 2.0 kN and following parameters were recorded: applied compressive load as a function of time, intradiscal pressure as a function of time, intervertebral pressure as a function of time for anterior and lateral edges of the vertebra, strain as a function of time for anterior and lateral right and left sites of the vertebra, stress-relaxation of the complete segment as a function of time. All show very similar response to loading and stress-relaxation. However, annulus pressure did not respond to stress-relaxation. This was due to functional aspect of annulus.

Lumbar vertebrae are a heavily loaded component of human body. They are subjected to repetitive loading in daily activities. However, limited information on failure mechanism of lumbar vertebrae are available to date. Thus, the need to develop an analytical model to predict stress-fracture characteristics of vertebral body. A linear elastic fracture mechanics approach has been considered and a mathematical model has been proposed so that the predictions can be made more easily related to the occurrence of injury. Study reveals that for a person weighing 1334 N and lifting a weight of 345 kg during squat exercise causes a vertebral stress-fracture at 12 repetitive standing lifting. While same load at lowest position yields a stress-fracture at less than 3 lifting. Numerical study shows that for change of position from standing to lowest position resultant compressive force acting on spine increases by two times whereas the possibility of stress-fracture increases by five times. Similarly at dead lift exercise, lifting 325 kg from standing to lowest position increases resultant compressive forces on vertebrae by 2.5 times. However, stress-fracture ratio increases by six times. Study reveals that for a person weighing 800 N (height = 1.8 m) and lifting a weight of 900 N, vertebrae can be subjected to stress-fracture by three cyclic lifting. Rate of injury is dependent on flexion angle i.e. as flexion angle increases, so does rate of injury.Copyright © 2011 by ASME

Biomedical Engineering in the Millennium is building the future of biology and medicine. New products, from biotechnology and novel devices for diagnosis and treatment, are marketed through interactions between universities, medical centers, small start-up companies, and large, more established firms. The role of biomedical engineering in the 21st century has already been highlighted by Ranu as far as research, education and space age technologies are concerned. Therefore, educating the modern biomedical engineering students in design processes is extremely important. This paper highlights how biomedical engineering design is taught for the first time to King Saud University students in Saudi Arabia. The conclusion drawn from this is that for the first time an innovative design course has been developed to teach the biomedical engineering students at King Saud University to meet the needs of tomorrow’s biomedical engineers.Copyright © 2011 by ASME

(1993). Product Liability of Medical Devices and Orthopaedic Implants: A Conference Report. Biomaterials, Artificial Cells and Immobilization Biotechnology: Vol. 21, No. 1, pp. 47-52.

A 3-D Foot Print Device was developed to measure the plantar foot pressures for normal and diabetic patients with neurotrophic ulcers. The results show that patients with peripheral neuropathy develop very high forefoot pressures as compared to normal segment of the populations. Bubble technology and new memory biomaterials insoles were used to reduce these forefoot pressures combined with providing new custom made shoes.Copyright © 2010 by ASME

An intradiscal pressure transducer (IDPT) and a set of intervertebral pressure transducer (IVPT) were developed to measure the pressures in the nucleus pulposus and around the annulus. Human lumbar spinal segments were loaded up to 2.0 kN and following parameters were recorded: applied compressive load as a function of time, intradiscal pressure as a function of time, intervertebral pressure as a function of time for anterior and lateral edges of the vertebra, strain as a function of time for anterior and lateral right and left sites of the vertebra, stress-relaxation of the complete segment as a function of time. All show very similar response to loading and stress-relaxation. However, annulus pressure did not respond to stress-relaxation. This was due to functional aspect of annulus.Copyright © 2010 by ASME

Water hyacinth (Eichhornia crassipes (Mart.) Solms) is a noxious aquatic weed. In India,it has infested more than 200,000 ha of water surface. During the course of present investigation it was proposed to make an extensive, planned and systematic survey of fungal pathogens that destroy the water hyacinth from the ponds of M.P. The study was undertaken to evaluate the compatibility of two or more fungi for integrated management of water hyacinth. Results clearly indicate that except Alternaria eichhorniae all the pathogens are compati- ble to each other. In vivo the lesion diameters were greater on water hyacinth leaves when combination of pathogens were used than indi- vidual pathogens. The Alternaria alternata, Curvularia lunata and Fusarium pallidoroseum combination resulted in maximum disease devel- opment followed by A. alternata with C. lunata, A. alternata with F. pallidoroseum and C. lunata with F. pallidoroseum. Thus, it can be con- cluded that better management of the weed can be achieved by using combination of pathogens.

A linear elastic fracture mechanics approach has been considered to understand the impact behavior of ankles and knees due to jumping. By using a crack increment model and a fatigue crack propagation model, simulation of the fracture due to repetitive jumps are evaluated. To aid the numerical calculation, an experimental study on standing jump by two Indian field hockey players on a force plate under standardized conditions were also carried out. The study reveals that 19 jumps are sufficient to cause micro-fracture of bone for a net force of 2879 N. This analysis may further help in understanding of fracture fixation of bone.

Low-back pain can affect almost anyone at any time. In the United States, 8–15 percent [Ranu, 1] of back injuries involve the spinal discs, which act as a cushion between each vertebra. When a human spinal disc slips or herniates, part or all of it bulges out from its usual setting between the vertebrae (Figure 1).

To gain further insight into the biomechanics of the human intervertebral disc and to determine a potential mechanism for causation and relief of symptoms related to a herniated disc, the pressure-volume relation was determined within the nucleus pulposus. Pressure was measured continuously within the nucleus pulposus in 17 intact lumbar discs from human cadavers by means of a miniature strain gauge at the tip of a size 4 French (1.3 mm) catheter inserted into the nucleus pulposus. The volume of the nucleus pulposus was increased at the slow, continuous rate of 0.034 ml/min by the pump regulated infusion of saline coloured with methylene blue. In 12 unloaded discs, nucleus pulposus pressure rose in a linear fashion (linear r = 0.96) from an initial mean pressure of 174 (SD 81) kPa. The mean rate of pressure rise was 327 (SD 109) kPa/ml volume increase. The peak pressure measured was 550 kPa; this was slightly higher than the capability of the transducer. Similar linear relations were obtained during infusion of saline into five vertically loaded discs fixed at the deformation produced by a 9.1 kg weight. The data define the pressure-volume relation within the disc and show that the nucleus pulposus, surrounded by the relatively inelastic annulus and the solid vertebral end plates, has the properties of a tight hydraulic space in which a large pressure rise will regularly result from a small increase in volume. Presumably the opposite is also true. The data may provide a biomechanical basis for the physiological variation in symptoms related to the disc, and for any benefits obtained from interventions designed to remove disc tissue.

The specific antigenicity of pentaglycine bridges in cell walls ofS. aureus was investigated. The antistaphylococcal sera (against11 Oeding strains ofS. aureus) were found to contain antibodies of two different specificities against polyglycyl peptides; one type reacted with polyglycyl peptides with a free amino terminus and the other with polyglycyl peptides with a free carboxyl terminus. These antibodies were assayed by passive hemagglutination with tanned sheep red cells sensitized with N-polyglycyl-BSA (containing polyglycyl peptides with a free amino terminus) or with C-polyglycyl-BSA (containing polyglycyl peptides with a free carboxyl terminus). Only the antibodies against N-polyglycyl peptides were absorbed byS. aureus strains and byS. epidermidis. Heterologous bacterial species failed to absorb antibodies of either specificity. Antibodies against polyglycyl peptides were used to confirm the mechanism of action of penicillin onS. aureus cell wall.

A finite element model of a complete vertebra was formulated from a previously developed bilaterally symmetric model. This model was verified by comparing its results to those of the previous model and by ensuring that the output was bilaterally symmetric. The applied nodal loads were checked against experimentally measured pressures on the vertebral endplate. Simulations of complete and partial laminectomies on one side of a vertebra were performed. High tensile stresses occurred in the pedicle and in the region of the pars interarticularis as a result of surgery, particularly when the superior half of the lamina was removed.

In heme-deficient reticulocyte lysates a translational inhibitor which regulates protein synthesis is formed or activated. To define the mechanism of action of the translational inhibitor (RI), RI was partially purified. We have utilized the isolated RI to examine its relationship to the translational inhibitor formed in situ in heme-deficiency, some quantitative aspects of inhibition of protein synthesis, and the relationship of RI concentration to the initiation factor (IF-MP) which forms a ternary complex with Met-tRNAf and GTP (IF-MP-Met-tRNAf-GTP). The results demonstrate that the activity of isolated RI is related to the in situ heme-deficiency inhibitor by several criteria: (a) the biphasic kinetics of inhibition manifested by RI in lysates containing optimal levels of hemin are very similar to those observed in heme-deficiency, i.e., an initial period in which several rounds of protein synthesis proceed at the control rate followed by an abrupt decline in the rate of protein synthesis. (b) Both inhibitions are accompanied by the disaggreagation of polyribosomes with a concomitant increase in 80S ribosomes. (c) Both inhibitions are reversed by IF-MP. The isolated RI blocked protein synthesis in lysates at temperatures ranging from 15 degrees to 30 degrees. Although the rate of protein synthesis was a function of the temperature of incubation, the number of rounds of protein synthesis prior to shut-off was essentially the same at various temperatures. When RI was added to lysates, at increasing intervals after the start of incubation, the period of synthesis before shut-off (lag) progressively decreased. The inhibition of protein synthesis by RI was immediately reversed by the addition of IF-MP. The extent of reversal increased with increasing concentrations of IF-MP; at low levels of RI almost complete reversal of inhibition by IF-MP was obtained. However, at high levels of RI which did not appreciably increase the degree of inhibition of protein synthesis, equivalent amounts of IF-MP were less effective in reversing inhibition. These results suggest that the inhibition of protein synthesis by the isolated inhibitor involves the initiation factor IF-MP.

The heme-regulated translational inhibitor (HRI) has been purified 4800-fold. On electrophoresis in sodium dodecyl sulfate/polyacrylamide gel, the purified HRI showed one major polypeptide band. The purified HRI inhibits protein synthesis in lysates containing optimal levels of hemin with inhibition kinetics which parallel those observed in heme-deficiency. Data are presented which are consistent with an enzymatic function of HRI in the inhibition of protein synthesis. The HRI is an adenosine 3':5'-cyclic monophosphate independent protein kinase which phosphorylates the small subunit (38,000) but not the large subunits (52,000 and 50,000) of the initiation factor which forms a ternary complex with Met-tRNAf and GTP. This evidence supports the hypothesis that inhibition of protein synthesis by HRI involves the phosphorylation of the initiation factor. These findings are discussed in relation to various models for the regulation of protein kinase activity by heme. (see article).

Summary 80S ribosomes from skeletal muscle of diabetic rats were more susceptible than normal to dissociation by the initiation factor EIF-3; the increased sensitivity to dissociation was a property of the 60S subunit. Increased dissociation may be a reflection of the instability of diabetic 80S couples resulting from a change in the structure of the large subunit.

In the absence of added hemin, protein synthesis in rabbit reticulocyte lysates proceeds at maximal linear rates for several minutes and then ceases abruptly. Inhibition involves the action of a translational inhibitor whose formation is regulated by hemin. Addition of the isolated inhibitor to hemin-supplemented lysates produces an inhibition of protein chain initiation similar to that observed in heme-deficiency. The inhibitor has been purified over 300-fold and contains a protein kinase activity that copurifies with the inhibitory function. With calf thymus histone II as the phosphate receptor, the inhibitor-associated protein kinase requires ATP as the phosphorylating agent. Cycle AMP stimulates kinase activity 5- to 8-fold; the concentration of cycle AMP required for halfmaximal activity is 4 X 10-8 M. Preincubation of the inhibitor in the presence of cyclic AMP significantly reduces cyclic AMP-dependent phosphorylation and inhibitory activity. The corresponding protein kinase activity from hemin-supplemented lysates displays reduced cyclic AMP-dependency and little or no inhibitory activity. These findings suggest that the protein kinase activity associated with the purified translational inhibitor is involved in the mechanism of inhibition of initiation observed in hemedeficient reticulocyte lysates.

Physical, dielectric, piezoelectric and electromechanical parameters have been reported for bone and its two major constituents i.e. collagen and apatite, for their characterization as ultrasonic transducer materials. Collagen and apatite have been extracted from full bone using well known methods. These materials have been used to prepare simple disc-shaped test pieces (dimensions: diameter 10 mm and thickness 1.0 ± 0.01 mm). The variation of various electrical parameters with frequency in the region (1–108 MHz) is examined for these materials. These include impedance, phase angle, relative voltage output, quality factor ‘Q’, dielectric constant and resistivity. The data so obtained are compared with those for ceramic and quartz transducers. The observations on impedance, phase and relative voltage output for bone materials indicate that the first resonance peak falls around 56 MHz followed by second and third harmonics around 112 MHz and 168 MHz respectively. A low ‘Q’ value suggests a fairly wide band transducer, while other parameters compare favourably with ceramic and quartz materials. Bone material has also been used to obtain a transducer in the standard configuration and velocity dispersion in the frequency range 1–108 MHz is examined.

A finite element model of a complete vertebra has been formulated. It is used to simulate the laminectomy and Harrington rod procedures. The results indicate that high tensile stresses occurred on the affected side in the region of the pars interarticularis after laminectomy. High tensile stresses near the pars interarticularis and at the posterior junction of lamina and pedicles are predicted due to Harrington rod loading.

Vanadate inhibits protein chain initiation in rabbit reticulocyte lysates. The evidence that supports this conclusion is as follows: (i) the biphasic kinetics of inhibition in which protein synthesis is maintained at the control rate for 1-2 min is followed by an abrupt decline in the rate of synthesis; (ii) inhibition is associated with a marked disaggregation of polyribosomes and a concomitant increase in 80S ribosomes; and (iii) vanadate concentrations that inhibit protein chain initiation do not inhibit polypeptide chain elongation or the aminoacylation of tRNA. In partial reactions of protein chain initiation, vanadate concentrations that inhibit protein synthesis have no detectable effect on the formation of eukaryotic initiation factor eIF-2-promoted ternary complex with Met-tRNAf and GTP and on the assembly of 40S ribosomal subunit-Met-tRNAf complexes. On the addition of mRNA, the 40S ribosomal subunit-Met-tRNAf complexes also are transformed into 80S ribosome-mRNA-Met-tRNAf complexes, termed 80S initiation complexes. In vanadate-treated samples, however, these 80S initiation complexes are defective and unable to proceed beyond this step.

The effect of various sulfhydryl reagents on the ribosomes of Bacillus subtilis was studied. The 70 S ribosomes were completely dissociated into 30 S and 50 S subunits by appropriate concentrations of p -chloromercuribenzoic acid (PCMB) and 5,5′-dithio- bis -(2-nitro-benzoic acid). The N -ethylmaleimide and iodoacetamide failed to dissociate the ribosomes even at relatively high concentrations. The rate of dissociation of ribosomes by PCMB varied with the concentration of ribosomes. A progressive decrease in the rate of dissociation was observed as the concentration of ribosomes in the reaction mixture was increased. The PCMB-induced ribosomal subunits were unable to reassociate into 70 S monomers unless they were dialyzed against buffer containing β-mercaptoethanol. On the average, four molecules of PCMB per 70 S ribosome and two molecules of PCMB per each 30 S and 50 S subunit were bound. The number of PCMB molecules bound per ribosome did not change with increasing concentrations of PCMB, even though higher concentrations of PCMB resulted in dissociation of ribosomes into subunits.

A methodology is described for measuring the centre of pressure for successive steps during stance phase. Three persons were assessed, one normal, one below knee amputee and one having suffered from poliomyelitis. The clinical significance of this parameter of gait as measured by the miniature shoe-borne load cells is highlighted.

Discrimination between eukaryotic and prokaryotic, and formylated and non-formylated, initiator tRNAs by eukaryotic initiation factor EIF-3

Man has recognized carbon as an implant material well tolerated by the body for many years. Indeed, carbon in an impure form (Indian ink) was first used in the making of tatoos. Most recently carbon has been used in a filamentous form of high strength. These carbon fibers are produced in long tows of 40,000 fibers, each with a cross sectional area of about 7μ (Figure 1), by heating acrylic fibers to high temperature. This causes the noncarbon components to be removed while maintaining the molecular structure (scaffold) of the acrylic. Fibers can be chopped into short lengths and used to reinforce polyethylenes (8, 11, 12). These reinforced plastics have-twice the strength and ten times the stiffness of their non-reinforced counterparts, but suffer only one tenth as much creep when subjected to a load (11). Long tows of carbon fibers are used in tendon and ligament replacement (1, 2, 4, 5, 6, 7, 9, 10). This application warrants further investigation because of the apparent ability of the carbon fibers to induce the formation of ligaments and tendons (3, 4, 5, 6, 7).

Protein chain initiation in reticulocyte lysates is inhibited by (a) heme-deficiency, (b) low levels of double-stranded RNA, and (c) a purified translational inhibitor isolated from heme-deficient lysates. Previous studies have shown that the inhibitions produced by heme-deficiency and double-stranded RNA are prevented by 3': 5'-cyclic AMP, and that GTP, but not ATP, prevents the inhibition of heme-deficiency. In view of the recent finding that the inhibitor purified from heme-deficient lysates is associated with a protein kinase which appears to be involved in the mechanism of inhibition, the effects of cyclic AMP, GTP, and ATP on the three modes of inhibition were examines. In all three types of inhibition, cyclic AMP or GTP (a) prevents the onset of inhibition when added at zero time, and (b) restores protein synthesis in inhibited lysates. In contrast to these effects, ATP potentiates each inhibition, and blocks reversal of inhibition by cyclic AMP or GTP. On the basis of these and earlier findings, we propose that (a) these inhibitions involve the phosphorylation by protein kinases of the Met-tRNAf binding factor and/or a related site(s) on the 40S ribosomal subunit; and (b) cyclic AMP, GTP, and ATP exert their effects by their actions on this phosphorylation mechanism.

Fracture of the fibrous networks of normal and irradiated rat dermis have been studied using the SEM. The implications of these observations are discussed with regard to the mechanical behaviour of the tissue in the living animal. It is shown that after radiation the normal fibrous structure of collagen is replaced by a solid mat which is ill adapted to support stress, so that rupture at low stress levels is inevitable.

The increasing use of metals as implant materials in orthopaedic surgery has stimulated a considerable amount of interest among researchers and orthopaedic surgeons enabling the study of corrosion, wear, hypersensitivity, toxcity and carcinogenicity (Furst and Haro, 1960; Mears, 1979; Woodman, 1980). Partly, the corrosion Phenomena is due to the metal implant ionization in living tissue (Ferguson et al, 1960; Lautenschlager et al, 1974). Corrosion is a complex electrochemical deterioration of metals (Clark and Hickman, 1953). Futhermore, corrosion is referred to as a combination of oxidation and reduction of reactions at the implant-tissue interface. The basic reactions in corrosion are the removal of positive metal ions from their positions in the metal crystal lattice. This is called an anodic reaction. Similarly, the freed electrons, as a result of removed cations, also react to oxygen and hydrogren molecules in tissues to form hydroxyle. This is defined as cathodic reactions at the metal-tissue interface (Mears, 1979).

To define the mechanism of regulation of the protein kinase that is activated in heme deficiency and that inhibits initiation of protein synthesis, we have isolated and purified the heme-reversible form of the protein kinase from rabbit reticulocytes. The inhibitory activity is found in a single band after polyacrylamide gel electrophoresis under nondenaturing conditions. It migrates as a 95,000-dalton polypeptide in 15% sodium dodecyl sulfate/polyacrylamide gels. This purified inhibitor becomes self-phosphorylated in the presence of ATP; the phosphorylated protein and the inhibitory activity copurify. The inhibitor produces characteristic biphasic kinetics of inhibition in reticulocyte lysates and phosphorylates the 38,000-dalton subunit of eukaryotic initiation factor 2 (eIF-2); the inhibition is reversed by added eIF-2. In contrast to the heme-irreversible inhibitor, this heme-reversible inhibitor is no longer inhibitory after incubation with 20 micron hemin. Incubation with hemin also inhibits self-phosphorylation. Preincubation of the heme-reversible inhibitor in the presence of ATP potentiates the inhibition of protein synthesis in the subsequent incubation, as does treatment with N-ethylmaleimide. Phosphorylation of the heme-reversible inhibitor and inhibition of protein synthesis in the lysate due to phosphorylation of eIF-2 appear to be related. These findings suggest that hemin acts directly on the heme-reversible inhibitor.

Heme deficiency in rabbit reticulocytes and their lysates leads to the activation of a heme-regulated translational inhibitor (HRI) which causes the cessation of polypeptide initiation. HRI is a protein kinase that specifically phosphorylates the 38,000-dalton subunit of eukaryotic initiation factor 2 (eIF-2). eIF-2 binds Met-tRNA f and GTP in ternary complex. As a continuation of the studies on the molecular basis of the inhibition of the formation of 40S ribosomal subunit-Met-tRNA f complexes by HRI [Ranu, R. S., London, I. M., Das, A., Dasgupta, A., Majumdar, A., Ralston, R., Roy, R. & Gupta, N. K. (1978) Proc. Natl. Acad. Sci. USA 75, 745-749], we describe here the isolation and some characteristics of a factor that is required for the HRI-catalyzed inhibition of eIF-2-promoted ternary complex formation. In the presence of 1 mM Mg 2+ , ternary complex formation by eIF-2 is dependent on the presence of this stabilization factor (SF). Under these conditions, SF increases the rate and the extent of ternary complex formation. This finding suggests that the interaction of SF with eIF-2 causes a conformational change that stabilizes eIF-2 and promotes efficient ternary complex formation by increasing the affinity of eIF-2 for GTP and Met-tRNA f . In the absence of Mg 2+ , however, eIF-2 efficiently forms the ternary complex and SF has little effect on its ternary complex formation capacity—hence, the name eIF-2 stabilization factor (SF). In the presence of SF, HRI markedly inhibits (70-80%) the ternary complex formation capacity of eIF-2. The inhibitory effect requires both HRI and ATP. Under these conditions, HRI phosphorylates only the 38,000-dalton subunit of eIF-2. Both the rate and the extent of the SF-dependent ternary complex formation are inhibited. These findings are consistent with the idea that phosphorylation causes a conformational change in eIF-2 such that its interactions with other initiation factors in the formation and the binding of ternary complex to 40S ribosomal subunits are inhibited.

Publisher Summary This chapter describes the regulation of eukaryotic protein chain initiation by protein kinases and heme. Reticulocyte lysates provide a model system for studies on the regulation of protein synthesis owing to several unique properties. They include an efficient rate of initiation, the extensive synthesis of one major protein species, and the complete dependence of protein synthesis on exogenous hemin. In the presence of optimal concentrations of added hemin, protein synthesis proceeds at linear rates for prolonged periods. During the period of linear synthesis, the polyribosomes are maintained, and initiation factors are utilized catalytically. In efficient lysates, the rate of globin synthesis is comparable to the in vivo rate. In the absence of added hemin, protein synthesis proceeds at the control rate for several minutes, and then declines abruptly yielding characteristic biphasic kinetics of inhibition. The studies have established that the inhibition is mediated through a translational inhibitor which is rapidly activated in the absence of heme.

In vitro thermal properties of human cortical bone have been measured using a specially developed technique. The technique enables accurate measurement of the coefficient of thermal expansion and contraction and the average values have been measured to be 27.5 ± 3.9 × 10−6 mm/°C for expansion and 27.2 ± 5.2 × 10−6 mm/°C for contraction.

A previous study demonstrated that the translational inhibitor from lysates of heme-deficient rabbit reticulocytes is associated with a protein kinase activity. Chromatography of this inhibitor preparation on phosphocellulose yields two distinct protein kinase activities, PC1 and PC2. PC1, which consitutes about 90% of the activity in the unresolved preparation, does not inhibit protein synthesis in lysates, but actively phosporylates calf thymus histone II in a 3':5'-cyclic AMP-denpendent reaction. PC2 contains the translational inhibitor, phosphorylates histone poorly, and is not cyclic AMP-dependent. While [gamma-32P]ATP as the phosphate donor, the two kinase fractions were analyzed with the putative substrates, salt-washed 40S ribosomal subunits, and the initiation factor that mediates the binding of Met-tRNAf to the 40S subunit. PC1 is inactive with the initiation factor, but phosphorylates 40S subunits at a single major site that migrates as a 31,000-dalton band in sodium dodecyl sulfate-acrylamide gels; phosphorylation requires cyclic AMP. Similar phosphorylation of the reticulocyte 40S site (31,000 daltons) can be demonstrated with other cyclic AMP-dependent kinases from reticulocytes, rat liver, and bovine heart muscle. PC2 phosphorylates the small subunit (38,000 daltons) but not the large subunit(s) of the initiation factor; the reaction does not require cyclic AMP. PC2 does not phosphorylate 40S subunits. In the presence of 40S subunits, the initiation factor appears to be rapidly bound in a manner that effectively blocks phosphorylation of the initiation factor by PC2; under the same conditions phosphorylation of the 40S subunit by PC1 is not affected. The initiation factor has been shown to reverse the inhibitions of protein chain initiation induced in lysates by heme deficiency, double-stranded RNA, oxidized glutathione, or the purified translational inhibitor. The observation that the Met-tRNAf binding factor is phosphorylated by PC2 supports the hypothesis that this initiation factor is a target for the action of the translational inhibitor activated in heme deficiency.

An engineering approach to functional assessment has been utilized to assist the moderate-to-severely physically handicapped. These computer-aided assessments are directed at work, keyboard operation and driving. In order to improve the quality of life for this population, independent living systems, recreational and mobility aids, and automated retrieval systems for information on assistive devices have been developed. This paper discusses their implementation and applications.

Pressures in the nucleus pulposus and under the annulus fibrosus have been measured, using the specially developed miniature pressure transducers, when the vertebral segment was subjected to physiological loading. Strain data and stress-relaxation were also measured. Results show that pressures are linear with loading. Pressure variations within the nucleus are due to disc degeneration.