A demonstration of the utility of fractional experimental design for finding optimal genetic algorithm parameter settings

This paper demonstrates that the use of sparse experimental design in the development of the structure for genetic algorithms, and hence other computer programs, is a particularly effective and efficient strategy. Despite widespread knowledge of the existence of these systematic experimental plans, they have seen limited application in the investigation of advanced computer programs. This paper attempts to address this missed opportunity and encourage others to take advantage of the power of these plans. Using data generated from a full factorial experimental design, involving 27 experimental runs that was used to assess the optimum operating settings of the parameters of a special genetic algorithm (GA), we show that similar results could have been obtained using as few as nine runs. The GA was used to find minimum cost schedules for a complex component assembly operation with many sub-processes

Reward prediction error in the ERP following unconditioned aversive stimuli

Reinforcement learning in humans and other animals is driven by reward prediction errors: deviations between the amount of reward or punishment initially expected and that which is obtained. Temporal difference methods of reinforcement learning generate this reward prediction error at the earliest time at which a revision in reward or punishment likelihood is signalled, for example by a conditioned stimulus. Midbrain dopamine neurons, believed to compute reward prediction errors, generate this signal in response to both conditioned and unconditioned stimuli, as predicted by temporal difference learning. Electroencephalographic recordings of human participants have suggested that a component named the feedback-related negativity (FRN) is generated when this signal is carried to the cortex. If this is so, the FRN should be expected to respond equivalently to conditioned and unconditioned stimuli. However, very few studies have attempted to measure the FRN’s response to unconditioned stimuli. The present study attempted to elicit the FRN in response to a primary aversive stimulus (electric shock) using a design that varied reward prediction error while holding physical intensity constant. The FRN was strongly elicited, but earlier and more transiently than typically seen, suggesting that it may incorporate other processes than the midbrain dopamine system

Genetic variation at hair length candidate genes in elephants and the extinct woolly mammoth

<p>Abstract</p> <p>Background</p> <p>Like humans, the living elephants are unusual among mammals in being sparsely covered with hair. Relative to extant elephants, the extinct woolly mammoth, <it>Mammuthus primigenius</it>, had a dense hair cover and extremely long hair, which likely were adaptations to its subarctic habitat. The fibroblast growth factor 5 (<it>FGF5</it>) gene affects hair length in a diverse set of mammalian species. Mutations in <it>FGF5 </it>lead to recessive long hair phenotypes in mice, dogs, and cats; and the gene has been implicated in hair length variation in rabbits. Thus, <it>FGF5 </it>represents a leading candidate gene for the phenotypic differences in hair length notable between extant elephants and the woolly mammoth. We therefore sequenced the three exons (except for the 3' UTR) and a portion of the promoter of <it>FGF5 </it>from the living elephantid species (Asian, African savanna and African forest elephants) and, using protocols for ancient DNA, from a woolly mammoth.</p> <p>Results</p> <p>Between the extant elephants and the mammoth, two single base substitutions were observed in <it>FGF5</it>, neither of which alters the amino acid sequence. Modeling of the protein structure suggests that the elephantid proteins fold similarly to the human FGF5 protein. Bioinformatics analyses and DNA sequencing of another locus that has been implicated in hair cover in humans, type I hair keratin pseudogene (<it>KRTHAP1</it>), also yielded negative results. Interestingly, <it>KRTHAP1 </it>is a pseudogene in elephantids as in humans (although fully functional in non-human primates).</p> <p>Conclusion</p> <p>The data suggest that the coding sequence of the <it>FGF5 </it>gene is not the critical determinant of hair length differences among elephantids. The results are discussed in the context of hairlessness among mammals and in terms of the potential impact of large body size, subarctic conditions, and an aquatic ancestor on hair cover in the Proboscidea.</p

Intussusception of the small bowel secondary to malignant metastases in two 80-year-old people: a case series

<p>Abstract</p> <p>Introduction</p> <p>Small bowel intussusception is rare in adults and accounts for one percent of all bowel obstructions. Malignancy is the etiologic agent in approximately 50 percent of all cases.</p> <p>Case presentation</p> <p>Our first patient was an 80-year-old Caucasian woman with signs and symptoms of intermittent bowel obstruction for the last 12 months. Pre-operative investigation by abdominal computed tomography scanning revealed an obstruction at the ileocecal valve. Exploratory laparotomy revealed an ileocecal intussusception. She underwent an enterectomy. Histological examination showed metastatic breast cancer (lobular carcinoma). Our patient had previously undergone a mastectomy due to carcinoma three years earlier.</p> <p>Our second patient was an 80-year-old Caucasian man with signs and symptoms of acute bowel obstruction. Pre-operative investigation by abdominal computed tomography scanning showed an intussusception in the proximal part of the small bowel. Exploratory laparotomy revealed a jejunojejunal intussusception. He underwent an enterectomy. Histological examination showed metastatic melanoma. Our patient had a prior history of a primary cutaneous melanoma which was excised two years ago.</p> <p>Conclusion</p> <p>Pre-operative determination of the etiologic agent of intussusception in the small bowel in adults is difficult. Although a computed tomography scan is very helpful, the diagnosis of intussusception is made by exploratory laparotomy and histological examination defines the etiologic agent. A prior malignancy in the patient's history must be taken under consideration as a possible cause of intussusception.</p