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Biomedical subjects

P Merz

Publications and source records attributed to P Merz.

7 recordsLinked to original sources

Fitness landscapes, memetic algorithms, and greedy operators for graph bipartitioning.

The fitness landscape of the graph bipartitioning problem is investigated by performing a search space analysis for several types of graphs. The analysis shows that the structure of the search space is significantly different for the types of instances studied. Moreover, with increasing epistasis, the amount of gene interactions in the representation of a solution in an evolutionary algorithm, the number of local minima for one type of instance decreases and, thus, the search becomes easier. We suggest that other characteristics besides high epistasis might have greater influence on the hardness of a problem. To understand these characteristics, the notion of a dependency graph describing gene interactions is introduced. In particular, the local structure and the regularity of the dependency graph seems to be important for the performance of an algorithm, and in fact, algorithms that exploit these properties perform significantly better than others which do not. It will be shown that a simple hybrid multi-start local search exploiting locality in the structure of the graphs is able to find optimum or near optimum solutions very quickly. However, if the problem size increases or the graphs become unstructured, a memetic algorithm (a genetic algorithm incorporating local search) is shown to be much more effective.

Algorithms↗

Cortisol reaction in success and failure condition in endogenous depressed patients and controls.

The authors studied differences in cortisol response to controllable and uncontrollable stress and its relationship to Seligman's theory of learned helplessness in hospitalized unipolar depressed patients (11 nontreated, acutely depressed; 11 treated patients) and 11 age and sex matched controls hospitalized for traumatic surgery. Control and lack of control were achieved by induction of success and failure in a simple number addition test and applied in balanced order on 2 consecutive days. Saliva cortisol samples were collected before and after the test. No group differences in baseline cortisol levels were observed. Cortisol increased after uncontrollable and decreased after controllable stress in control patients, whereas cortisol decreased after both conditions in the acutely depressed group and less so in the treated group, although they were as emotionally upset after failure as controls. Thus, the normally observed ability of the neuroendocrine system to discriminate between controllable and uncontrollable stress deteriorates with increasing severity of depression.

Adaptation, Psychological↗

beta-amyloid protein of Alzheimer's disease is found in cerebral and spinal cord vascular malformations.

Congo/Red deposition with birefringence to polarized light was demonstrated focally in cerebrovascular malformations removed surgically from 4 older patients (ages 85, 74, 74, and 63), and in a spinal cord vascular malformation in a 76-year-old patient. Lesser degrees of Congophilic change were observed in cerebrovascular malformations screened from 4 of 10 patients between the ages of 30 and 59. No Congophilic change was seen in 10 cerebrovascular malformations removed from patients under 30 years of age. Congophilic areas in all cases decorated with W-2 and 85/45 polyclonal antibodies raised to peptide sequences of cerebrovascular beta-amyloid and beta-amyloid of senile plaques from patients with Alzheimer's disease. Thus, the amyloid in these vascular malformations is immunologically related to beta-amyloid protein. This finding provides another indication that vascular beta-amyloid deposition is not specific for Alzheimer's disease and suggests that an existing abnormality of vessels may be a predisposing factor.

Adolescent↗

Purification and characterization of myosin from calf brain.

Actomyosin complex was extracted from the brain cortex in a medium consisting of low salt, ATP, and EDTA, in the presence of protease inhibitors, followed by ammonium sulfate fractionation. Myosin was then purified from the actomyosin. Myosin obtained according to the procedure used was significantly contaminated with actin high (greater than 200,000 dalton) and low molecular weight proteins. Therefore, an alternative method based on affinity chromatography (Blue Dextran/Sepharose) and gel filtration (Sepharose 4B) was developed to purify myosin. This procedure yielded myosin that was greater than 95% pure as judged by electron microscopy and sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The subunit composition of purified brain myosin was monitored by sodium dodecyl sulfate-polyacrylamide gel also containing a urea gradient. A closely migrating triplet in the heavy chain and three light chains, LC1, LC2, and LC3, of Mr 21,000, 19,000, and 17,000, respectively, were observed. These findings raise the possibility of the existence of myosin isoenzymes in the brain. Brain myosin formed bipolar thick filaments in 0.075 M KCl and MgCl2. At low ionic strength, the Mg2+-ATPase activity of myosin was stimulated 3- to 3.5-fold in the presence of skeletal muscle f-actin. Brain myosin also hydrolyzed other nucleotides; the rate of hydrolysis was ITP greater than ATP approximately equal to CTP greater than GTP approximately equal to UTP. The substrate (ATP) saturation curve in the presence of 10 mM CaCl2 and 0.6 M KCl was complex and consisted of plateau regions. The Arrhenius plot of the Ca-ATPase data was linear, whereas with ITPase, it was biphasic with a break occurring around 20 degrees C.

Actins↗

Partial purification of neurofilament subunits from bovine brains and studies on neurofilament assembly.

The 200,000-dalton neurofilament subunit (P200) and the 160,000-dalton (P160) and 78,000-dalton (P78) neurofilament subunits were partially purified from bovine brain. Intact neurofilaments were prepared by high-speed and sucrose-zone centrifugation. The crude neurofilament was solubilized in 8 M urea solution containing pyridine, formic acid, and 2-mercaptoethanol. The solubilized neurofilament was purified by carboxymethyl (CM) cellulose column and hydroxylapatite column chromatography. The P200 was purified as separate from P160 and P78, but the P160 and P78 subunits were copurified on CM cellulose, hydroxylapatite, Bio-Gel A150m, and Sephadex G-150 column chromatography. Electron microscopy of these purified neurofilament subunits revealed the P200 subunit as a globular structure, and the P160 and P78 subunits as a rod-shaped structure extending up to 120 nm with a 8- to 12-nm width. In the presence of 200 mM KCl, 15 mM MgCl2, and 1 mM ATP, the purified subunits assembled into long filaments. Under the assembly condition, P160 and P78 subunits elongated up to 500 nm, but the longer filament formation required the presence of P200 subunits. The filaments formed in vitro were of two types: long straight filaments and intertwined knobby-type filaments. From these results, we have suggested that P160 and P78 form the neurofilament backbone structure and P200 facilitates the assembly of the backbone units into longer filaments.

Adenosine Triphosphate↗