Genetic localization

P-Lactamases are enzymes that hydrolyze the P-lactam ring of P-lactamantibiotics (penicillins, cephalosporins, monobactams and carbapenems). They are the most common cause of P-lactam resistance. Most enzymes use a serine residue in the active site that attacks the P-lactam-amid carbonyl group. The covalently formed acylester is then hydrolyzed to reactivate the P-lacta-mase and liberates the inactivated antibiotic. Metallo P-lactamases use Zn(II) bound water for hydrolysis of the P-lactam bond. P-Lactamases constitute a heterogeneous group of enzymes with differences in molecular structures, in substrate preferences and in the genetic localizations of the encoding gene (Table 1). 

Marquet, S., Abel, L., Hillaire, D., Dessein, H., Kali I, J., Feingold, J., Weissenbach, J. and Dessein, A.J. (1996) Genetic localization of a locus controlling the intensity of infection by Schistosoma mansoni on chromosome 5q31-q33. Nature Genetics 14, 181-184. 

Smith WC, Xiang L, Shen B. Genetic localization and molecular characterization of the nonS gene required for macrotetrolide biosynthesis in Streptomyces griseus DSM40695. Antimicrob. Agents Chemother. 2000 44 1809-1817. 

Pfister-Genskow, M., Weesner, G.D., Hayes, H., Eggen, A., Bishop M.D. (1997) Physical and genetic localization of the bovine cannabinoid receptor (CNRl) gene to bovine chromosome 9. Mamm. Genome. 8, 301-302. 

Richards, et. al. s idea is to use a genetic algorithm to search through a space of a certain class of cellular automata rules for a local rule that best reproduces the observed behavior of the data. Their learning algorithm (which was applied specifically to sequential patterns of dendrites formed by NH4 Br as it solidifies from a supersaturated solution) starts with no a-priori knowledge about the physical system. R, instead, builds increasingly sophisticated models that reproduce the observed behavior. 

Moreover, behaviors frequently arise that appear to involve some form of intelligent division of red and blue forces to deal with local firestorms and skirmishes, particularly those forces whose personalities have been evolved (via a genetic algorithm sec below) to perform a specific mission, It is important to point out that such behaviors are not hard-wired but rather an emergent property of a decentralized and nonlinear local dynamics, A small sampling of behaviors is shown below. 

On pharmacodynamic grounds, tumor resistance may be caused by such diverse mechanisms as the mutation or redundancy of topo II, the overexpression and preferred nuclear localization of proteasome a-type subunits (leading to a anomalous degradation of topo II), genetic deletion or loss-of-function mutations of p53, overexpression of ROS-detoxifying enzymes, overexpression of Bcl-2 (leading to a diminished cyt c release), etc. However, none of these factors would universally predict the development of anthracycline-resistance in a given tumor or another. 

EDMD is another X-linked muscular dystrophy, clinically and genetically completely distinct from DMD and BMD. Affected boys usually have onset in childhood of contractures (especially involving the Achilles tendons, elbows, and spinal muscles), humeroperoneal muscle weakness, and cardiac conduction defects, which tend to be mostly a problem in adult life and may necessitate insertion of a pacemaker. The gene for EDMD is known to map to Xq28, but this localization is... 

Genetic transmission in nemaline myopathy is the subject of some uncertainty. A Japanese study of 50 pedigrees came to the conclusion that autosomal dominant with reduced penetrance was the most probable mode. However a Finnish study presented evidence for autosomal recessive transmission. There is no evidence that severe and mild forms are genetically distinct and several pedigrees contain members showing widely differing clinical severity. A candidate gene for autosomal dominant nemaline myopathy has been localized to chromosome Iq 21—23. 

Hamet, P., Tremblay, J., Malo, D., Kunes, J., Hashimoto, T. (1990b). Genetic hypertension is characterized by the abnormal expression of a gene localized in major histocompatibility complex hsp70. Transplant. Proc. 22,2566-2567. 

To determine the optimal parameters, traditional methods, such as conjugate gradient and simplex are often not adequate, because they tend to get trapped in local minima. To overcome this difficulty, higher-order methods, such as the genetic algorithm (GA) can be employed [31,32]. The GA is a general purpose functional minimization procedure that requires as input an evaluation, or test function to express how well a particular laser pulse achieves the target. Tests have shown that several thousand evaluations of the test function may be required to determine the parameters of the optimal fields [17]. This presents no difficulty in the simple, pure-state model discussed above. 

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