A magnetic resonance imaging study of planum temporale asymmetry in men with developmental dyslexia

The influence of ionic strength and composition on the binding and inhibition of human leukocyte elastase by glycosaminoglycans with variable degree and position of sulfation was investigated. The kinetic mechanism of inhibition had a hyperbolic, mixed-type character with a competitive component that was promoted by low ionic strength, reduced by phosphate ions, and which also depended on the substrate and glycosaminoglycan structure. Enzyme binding was a cooperative phenomenon that varied with ionic strength and composition. The inhibition patterns correlated with the cationic character of elastase and with the distribution of arginines on its molecular surface, most notably with residues located in the vicinity of the substrate binding region. The order of affinity for elastase binding was chondroitin 4-sulfate < chondroitin 6-sulfate < dermatan sulfate, iduronate-containing derivatives being superior with respect to the glucuronate-containing counterparts. Additional sulfation at both the 4- and 6- positions or at the N- and 4-positions of the N-acetylgalactosamine moiety decidedly improved the inhibitory efficiency. The results highlight a fundamental physiological role of enzyme-glycosaminoglycan interactions. In the azurophil granule of the human polymorphonuclear neutrophil, elastase and other enzymes are bound to a matrix of chondroitin 4-sulfate because this is the only glycosaminoglycan that simultaneously offers good binding for enzyme compartmentalization together with prompt release from the bound state at the onset of phagocytosis.     

Childhood fibrous dysplasia presenting as blindness: a skull base approach for resection and immediate reconstruction

Fibrous dysplasia is an abnormal fibroosseous process of bone of unknown cause. The incidence of skull involvement varies, painless enlargement being the most common presenting symptom. Change in vision is a rare but recognized finding. We report a 3-year-old boy with extreme fibrous dysplasia involving the skull base, who presented with blindness. He underwent exposure osteotomies of the frontal bones and orbits to provide access for skull base tumor removal. The orbital roofs were reconstructed with microplate-fixed cranial grafts. One and one half years after tumor excision followed by immediate reconstruction, the boy retains facial symmetry, and his ocular function has not deteriorated.     

The use of cantilever bridges

Replacement of missing teeth with fixed bridgework often involves producing full crown retainers on teeth on both sides of an edentulous space. Unfortunately, this approach can result in the destruction of much healthy tooth tissue, and the clinician must balance the benefits of replacing missing teeth with the amount of tooth preparation required. Current thinking in restorative dentistry places the preservation of tooth tissue at a premium, and most practitioners are happy to use techniques that embrace this philosophy. Because of this, cantilever bridges have an increasing role in dental practice, where the replacement for a missing tooth or teeth has one or more abutments on only one side of the edentulous space, being unsupported at the other. Cantilever bridges fall into several types, depending on the number of abutments and types of retainers. This article describes the various cantilever bridge designs, considers the biomechanics of these restorations, and provides guidelines for their clinical use.     

Parameters affecting the use of the lac repressor system in eukaryotic cells and transgenic animals

Elements of the lactose operon were used to study parameters affecting gene expression in cultured cells and transgenic animals. A Lac repressor protein containing a nuclear transport signal was shown to inhibit expression of a reporter gene by interacting with lac operator sequences. In cultured cells, operator sequence, operator placement and induction parameters were all shown to be important for obtaining tight repression of a reporter gene followed by high level expression upon induction. Induction levels were also dependent on the reporter gene, with the luciferase gene yielding higher induction levels than the chloramphenicol acetyltransferase gene. In transgenic animals, the lacI mRNA was not detected in the C57BL/6 mouse strain until the animal was exposed to a demethylating agent. After 5-azacytidine treatment, expression of lacI mRNA was detected in the brain, heart, kidney, lung and ovary. In the FVB transgenic mouse strain, expression of lacI mRNA was detected without 5-azacytidine treatment in the kidney, liver, lung, and testes. Preliminary experiments with double transgenic animals containing both lacI and operator/luciferase transgenes showed a decrease in luciferase expression compared to the luciferase-only animals in both tissue extracts and transgenic fetal primary cultures, although IPTG induction was not achieved in these animals or primary cultures. The applicability and challenges of the system for regulation of gene expression are discussed.     

Selection of network and learning parameters for an adaptive neural robotic control scheme

This paper presents the results of a study in the design of a neural network based adaptive robotic control scheme. The neural network used here is a two hidden layer feedforward network and the learning scheme is the well-known backpropagation algorithm. The neural network essentially provides the inverse of the plant and acts in conjunction with a standard PD controller in the feedback loop. The objective of the controller is to accurately control the end position of a single link manipulator in the presence of large payload variations, variations in the link length and also variations in the damping constant. Based on results of this study, guidelines are presented in selecting the number of neurons in the hidden layers and also the parameters for the learning scheme used for training the network. Results also indicate that increasing the number of neurons in the hidden layer will improve the convergence speed of learning scheme up to a certain limit beyond which the addition of neurons will cause oscillations and instability. Guidelines for selecting the proper learning rate, momentum and fast backpropagation constant that ensure stability and convergence are presented. Also, a relationship between the r.m.s. error and the number of iterations used in training the neural network is established.     

Biochemical identification of transmembrane segments of the Ca(2+)-ATPase of sarcoplasmic reticulum

The transmembrane segments of sarcoplasmic reticulum Ca(2+)-ATPase were determined by trypsinization of cytoplasmic side-out intact sarcoplasmic reticulum vesicles. The membrane portion of tryptic digest comprising the transmembrane fragments, joined by the intravesicular segments, was separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis after labeling with fluorescein 5-maleimide in the presence of sodium dodecyl sulfate. In this way, seven fluorescent bands of tryptic fragments below 11 kDa were observed which were derived from 4 pairs of membrane spanning segments and one hydrophobic sequence at the C-terminal end. Two peptides of 10.8 and 10.6 kDa had the identical N-terminal sequence beginning at Glu826, representing the transmembrane segments M7 and M8 and their connecting loop. A band at 8.1 kDa contained one peptide beginning at Tyr36 (M1/loop/M2). A 7.7-kDa peptide starting at Leu253 (M3/loop/M4) and a 7.3-kDa peptide beginning at Ala752 (M5/loop/M6) were also observed. A band at 6.7 kDa contained two peptides, one beginning at Ser48 (M1/loop/M2) and another beginning at Tyr763 (M5/loop/M6). In addition, a 4-kDa peptide beginning at Met925 was observed. The size of this peptide did not allow for a complete pair of transmembrane segments, but this peptide could have been derived from trypsinolysis between the last pair of membrane spanning segments. These data therefore provide biochemical evidence for at least 8 transmembrane segments and perhaps two more at the C-terminal end of the enzyme.     

Ubiquitin expression in inclusion body myositis. An immunohistochemical study

Ubiquitin has been shown by immunohistochemical studies to be a component of many of the filamentous inclusion bodies that are known in neuropathology. In the current study, we examined the expression of ubiquitin in 14 cases of typical inclusion body myositis, in skeletal muscle specimens from four cases of typical amyotrophic lateral sclerosis, and in muscle specimens from three normal controls. In the cases of inclusion body myositis, rimmed vacuoles were ubiquitin immunoreactive in all cases. Intrasarcoplasmic inclusions were positive in the nine cases that had them. In four cases, there were positive intranuclear inclusions, and in seven, there was homogeneous staining of nuclei. Atrophic fibers and necrotic fibers were positive in 11 and nine cases, respectively. In the cases of amyotrophic lateral sclerosis, atrophic fibers were positive in three cases, and focal nuclear staining was seen in two. In one of the three control cases, a few atrophic fibers had faint sarcoplasmic positivity; no other staining was seen. We conclude that ubiquitin is a component of the inclusions that characterize inclusion body myositis. However, ubiquitin expression in skeletal muscle disease is not pathognomonic of inclusion body myositis.     

Grand Coulee Dam 70 Years Later: What Can We Learn?

This paper presents key findings from a case study on the Grand Coulee Dam conducted by the authors for the World Commission on Dams. The analysis demonstrates that the distribution of project benefits has been tilted in favour of irrigation interests and hydroelectric power users and that the project's major cost bearers have been riparian-based indigenous tribes of the Upper Columbia River. The study identifies lessons learned that are applicable to many large multi-purpose water resources development projects. Within the paper, the impacts of the following factors are discussed: low stakeholder participation in decision making; absence of just compensation to Native Americans and Canadian First Nations adversely affected by the loss of fishery resources; modernization of agricultural technology; differing stakeholder perceptions of project costs and benefits; and changes in values attached to anadromous fish. The lessons highlight the need for careful, broad-based a priori assessments of the irreversible and cumulative impacts of large water resources development projects as well as planned re-evaluations of water allocations and project operations.