COL4A1 Mutations Cause Ocular Dysgenesis, Neuronal Localization Defects, and Myopathy in Mice and Walker-Warburg Syndrome in Humans

Muscle-eye-brain disease (MEB) and Walker Warburg Syndrome (WWS) belong to a spectrum of autosomal recessive diseases characterized by ocular dysgenesis, neuronal migration defects, and congenital muscular dystrophy. Until now, the pathophysiology of MEB/WWS has been attributed to alteration in dystroglycan post-translational modification. Here, we provide evidence that mutations in a gene coding for a major basement membrane protein, collagen IV alpha 1 (COL4A1), are a novel cause of MEB/WWS. Using a combination of histological, molecular, and biochemical approaches, we show that heterozygous Col4a1 mutant mice have ocular dysgenesis, neuronal localization defects, and myopathy characteristic of MEB/WWS. Importantly, we identified putative heterozygous mutations in COL4A1 in two MEB/WWS patients. Both mutations occur within conserved amino acids of the triple-helix-forming domain of the protein, and at least one mutation interferes with secretion of the mutant proteins, resulting instead in intracellular accumulation. Expression and posttranslational modification of dystroglycan is unaltered in Col4a1 mutant mice indicating that COL4A1 mutations represent a distinct pathogenic mechanism underlying MEB/WWS. These findings implicate a novel gene and a novel mechanism in the etiology of MEB/WWS and expand the clinical spectrum of COL4A1-associated disorders

A Gigantic Shark from the Lower Cretaceous Duck Creek Formation of Texas

Author Contributions Conceived and designed the experiments: JAF SNS JAD-F. Analyzed the data: JAF SNS. Wrote the paper: JAF SNS. Site data for OMNH V1727 are available by request from the department of vert. paleontology at the (SN)OMNH.Three large lamniform shark vertebrae are described from the Lower Cretaceous of Texas. We interpret these fossils as belonging to a single individual with a calculated total body length of 6.3 m. This large individual compares favorably to another shark specimen from the roughly contemporaneous Kiowa Shale of Kansas. Neither specimen was recovered with associated teeth, making confident identification of the species impossible. However, both formations share a similar shark fauna, with Leptostyrax macrorhiza being the largest of the common lamniform sharks. Regardless of its actual identification, this new specimen provides further evidence that large-bodied lamniform sharks had evolved prior to the Late Cretaceous.Ye

A sliding-mode based smooth adaptive robust controller for friction compensation

In this paper, a new approach employing both adaptive and robust methodologies is proposed for stick-slip friction compensation for tracking control of a one degree-of-freedom DC-motor system. It is well known that the major components of friction are Coulomb force, viscous force, exponential force (used to model the downward bend of friction at low velocity) and position-dependent force. Viscous force is linear and Coulomb force is linear in parameter; thus, these two forces can be compensated for by adaptive feedforward cancellation. Meanwhile, the latter two forces, which are neither linear nor linear in parameters, can only be partially compensated for by adaptive feedforward cancellation. Therefore, a robust compensator with an embedded adaptive law to `learn' the upper bounding function on-line is proposed to compensate the uncancelled exponential and position-dependent friction. Lyapunov's direct method is utilized to prove the globally asymptotic stability of the servo-system under the proposed friction compensation method. Numerical simulations are presented as illustrations. (C) 1998 John Wiley & Sons, Ltd