A Specific Network Link and Path Likelihood Prediction Tool

Communications have always been a crucial part of any military operation. As the pace of warfare and the technological complexity of weaponry have increased, so has the need for rapid information to assess battlefield conditions. Message passing across a network of communication nodes allowed commanders to communicate with their forces. It is clear that an accurate prediction of communication usage through a network will provide commanders with useful intelligence of friendly and unfriendly activities. Providing a specific network link and path likelihood prediction tool gives strategic military commanders additional intelligence information and enables them to manage their limited resources more efficiently. In this study, Dijkstra\u27s algorithm has been modified to allow the Queueing Network Analyzer\u27s (QNA) analysis output to act as a node\u27s goodness metric. QNA\u27s calculation of the expected Total Sojourn Time for the completion of queueing and service in a node provides accurate measurement of expected congestion. The modified Dijkstra\u27s algorithm in the Generalized Network Analyzer (GNA) is verified and empirically validated to properly deliver traffic. It appropriately generates the fastest traffic path from a start node to a destination node. This implementation includes notification if input parameters exceed the network\u27s processing capability. GNA\u27s Congestion Control displays notification and informs the user certain network input parameters must be lowered (PTR or BSTR) or where certain nodes must be improved to maintain node stability. With this unstable node identification, users can determine which node needs attention and improvements. Once this instability is removed, a good QoS is achieved and analysis proceeds

Positive selection and propeptide repeats promote rapid interspecific divergence of a gastropod sperm protein

Male-specific proteins have increasingly been reported as targets of positive selection and are of special interest because of the role they may play in the evolution of reproductive isolation. We report the rapid interspecific divergence of cDNA encoding a major acrosomal protein of unknown function (TMAP) of sperm from five species of teguline gastropods. A mitochondrial DNA clock (calibrated by congeneric species divided by the Isthmus of Panama) estimates that these five species diverged 2-10 MYA. Inferred amino acid sequences reveal a propeptide that has diverged rapidly between species. The mature protein has diverged faster still due to high nonsynonymous substitution rates (\u3e25 nonsynonymous substitutions per site per 109 years), cDNA encoding the mature protein (89-100 residues) shows evidence of positive selection (D(n)/D(s) \u3e 1) for 4 of 10 pairwise species comparisons. cDNA and predicted secondary-structure comparisons suggest that TMAP is neither orthologous nor paralogous to abalone lysin, and thus marks a second, phylogenetically independent, protein subject to strong positive selection in free-spawning marine gastropods. In addition, an internal repeat in one species (Tegula aureotincta) produces a duplicated cleavage site which results in two alternatively processed mature proteins differing by nine amino acid residues. Such alternative processing may provide a mechanism for introducing novel amino acid sequence variation at the amino-termini of proteins. Highly divergent TMAP N-termini from two other tegulines (Tegula regina and Norrisia norrisii) may have originated by such a mechanism

Diversity of olfactomedin proteins in the sea urchin

AbstractOlfactomedin (OLF) domain proteins maintain extracellular protein-protein interactions in diverse phyla. Only one OLF family member, amassin-1, has been described from the sea urchin Strongylocentrotus purpuratus, a basal invertebrate deuterostome. Amassin-1 mediates intercellular adhesion of coelomocytes (immunocytes). Here we describe the protein structural features of four additional OLF proteins, the total for the genome being five. Phylogenetically, four of these proteins (the amassins) form a subgroup among previously identified OLF proteins. The fifth OLF protein is within the colmedin subfamily and contains a type II transmembrane domain, collagen repeats, and an OLF domain. Sea urchin OLF proteins represent an intermediate diversification between protostomes and vertebrates. Transcripts of all five OLF family members are in coelomocytes and adult radial nerve tissue. Transcripts for some OLF proteins increase during late larval stages. Transcript levels for amassin-1 increase 1,000,000-fold, coinciding with formation of the adult urchin rudiment within the larval body

The 10 sea urchin receptor for egg jelly proteins (SpREJ) are members of the polycystic kidney disease-1 (PKD1) family

<p>Abstract</p> <p>Background</p> <p>Mutations in the human polycystic kidney disease-1 (<it>hPKD1</it>) gene result in ~85% of cases of autosomal dominant polycystic kidney disease, the most frequent human monogenic disease. PKD1 proteins are large multidomain proteins involved in a variety of signal transduction mechanisms. Obtaining more information about members of the PKD1 family will help to clarify their functions. Humans have five hPKD1 proteins, whereas sea urchins have 10. The PKD1 proteins of the sea urchin, <it>Strongylocentrotus purpuratus</it>, are referred to as the Receptor for Egg Jelly, or SpREJ proteins. The SpREJ proteins form a subfamily within the PKD1 family. They frequently contain C-type lectin domains, PKD repeats, a REJ domain, a GPS domain, a PLAT/LH2 domain, 1–11 transmembrane segments and a C-terminal coiled-coil domain.</p> <p>Results</p> <p>The 10 full-length SpREJ cDNA sequences were determined. The secondary structures of their deduced proteins were predicted and compared to the five human hPKD1 proteins. The genomic structures of the 10 SpREJs show low similarity to each other. All 10 SpREJs are transcribed in either embryos or adult tissues. SpREJs show distinct patterns of expression during embryogenesis. Adult tissues show tissue-specific patterns of SpREJ expression.</p> <p>Conclusion</p> <p>Possession of a REJ domain of about 600 residues defines this family. Except for SpREJ1 and 3, that are thought to be associated with the sperm acrosome reaction, the functions of the other SpREJ proteins remain unknown. The sea urchin genome is one-fourth the size of the human genome, but sea urchins have 10 SpREJ proteins, whereas humans have five. Determination of the tissue specific function of each of these proteins will be of interest to those studying echinoderm development. Sea urchins are basal deuterostomes, the line of evolution leading to the vertebrates. The study of individual PKD1 proteins will increase our knowledge of the importance of this gene family.</p

Effects of the selective kainate receptor antagonist ACET on altered sensorimotor gating in a genetic model of reduced NMDA receptor function

The pathophysiology of schizophrenia may involve reduced NMDA receptor function. Accordingly, experimental models of NMDA receptor hypofunction may be useful for testing potential new antipsychotic agents and for characterizing neurobiological abnormalities relevant to schizophrenia. We demonstrated previously that mice under-expressing the NR1 subunit of the NMDA receptor show supersensitive behavioral responses to kainic acid and that a kainate receptor antagonist normalized altered behaviors in the mutant mice (NR1neo/neo). The present work examined effects of another selective kainate receptor antagonist, (S)-1-(2-Amino-2-carboxyethyl)-3-(2-carboxy-5-phenylthiophene-3-yl-methylpyrimidine-2,4-dione (ACET), on altered behavioral phenotypes in the genetic model of NMDA receptor hypofunction. ACET, at a dose of 15 mg/kg, partially reversed the deficits in prepulse inhibition produced by the mutation. The 15 mg/kg dose of ACET was also effective in reversing behavioral effects of the selective kainate agonist ATPA. However, ACET did not significantly reduce the increased locomotor activity and rearing behavior observed in the NR1neo/neo mice. These findings show that a highly selective kainate receptor antagonist can affect the deficits in sensorimotor gating in the NR1neo/neo mice. The results also provide further support for the idea that selective kainate receptor antagonists could be novel therapeutic candidates for schizophrenia

Increased sensitivity to kainic acid in a genetic model of reduced NMDA receptor function

The pathophysiology of schizophrenia may involve reduced NMDA receptor function and experimental models of NMDA receptor hypofunction have proven useful for characterizing neurobiological abnormalities potentially relevant to schizophrenia. The present study assessed behavioral responses and induction of Fos after administration of kainic acid to wild type mice (NR1+/+) and mice with genetically reduced NMDA receptor expression (NR1neo/neo). At a dose of 20 mg/kg kainic acid induced lethal seizures in 100% of the NR1neo/neo mice tested but produced no lethal seizures in the wild type mice. The NR1neo/neo mice also exhibited enhanced behavioral responses to kainic acid at a dose of 15 mg/kg but no lethal seizures were produced by this dose. A greater induction of Fos was observed in neocortical and limbic cortical regions of the NR1neo/neo compared to NR1+/+ mice after administration of 15 mg/kg kainic acid. In contrast, there were no differences between the genotypes in kainic acid induced of Fos in the amygdala, hippocampus, lateral septum, and nucleus accumbens. In order to determine if altered behavioral phenotypes of the NR1neo/neo mice could be related to increased sensitivity of kainate receptors to endogenous glutamate, effects of the highly selective kainate antagonist LY382884 were examined. The kainate antagonist reduced the exaggerated acoustic startle responses, deficits in prepulse inhibition of acoustic startle, and motor hyperactivity in the NR1neo/neo mice. These findings suggest that selective kainate receptor antagonists could be novel therapeutic candidates for schizophrenia

Neural activation deficits in a mouse genetic model of NMDA receptor hypofunction in tests of social aggression and swim stress

Mice with reduced expression of the NR1 subunit of the NMDA receptor (NR1 hypomorphic mice) display altered behavioral phenotypes that may relate to behavioral characteristics of schizophrenia. Altered phenotypes in the NR1 hypomorphs include marked deficits in species-typical behavioral interactions in tests of social aggression and social affiliation. To gain insight into neuroanatomical circuits disrupted by reduced NMDA receptor function, the present work compared regional brain activation in NR1 hypomorphic mice and their wild type controls after a resident-intruder test. Induction of Fos protein was used as an index of neuronal activation. Wild type mice exhibited robust induction of Fos in select brain regions, including specific nuclei of the hypothalamus and amygdala, lateral septum, and widespread regions of the cerebral cortex. Although the behavioral patterns were different for male and female mice, neuroanatomical patterns of Fos induction were remarkably similar for the two sexes. To determine socially specific components of Fos induction by the resident-intruder test, responses were compared for mice assessed in a test of general arousal and stress involving forced swim. Some common brain regions were activated by both tests but regionally specific differences were also found. The NR1 hypomorphic mice tested in the resident-intruder procedure displayed distinctly different behavioral interactions compared to the wild type mice and exhibited a significantly blunted Fos response in almost all brain regions. The mutant mice also exhibited reduced Fos in response to swim stress in specific brain regions. These data suggest that the NR1 hypomorphic mice have functional activation deficits in response to social challenge and swim stress

A functional genomic and proteomic perspective of sea urchin calcium signaling and egg activation

AbstractThe sea urchin egg has a rich history of contributions to our understanding of fundamental questions of egg activation at fertilization. Within seconds of sperm–egg interaction, calcium is released from the egg endoplasmic reticulum, launching the zygote into the mitotic cell cycle and the developmental program. The sequence of the Strongylocentrotus purpuratus genome offers unique opportunities to apply functional genomic and proteomic approaches to investigate the repertoire and regulation of Ca2+ signaling and homeostasis modules present in the egg and zygote. The sea urchin “calcium toolkit” as predicted by the genome is described. Emphasis is on the Ca2+ signaling modules operating during egg activation, but the Ca2+ signaling repertoire has ramifications for later developmental events and adult physiology as well. Presented here are the mechanisms that control the initial release of Ca2+ at fertilization and additional signaling components predicted by the genome and found to be expressed and operating in eggs at fertilization. The initial release of Ca2+ serves to coordinate egg activation, which is largely a phenomenon of post-translational modifications, especially dynamic protein phosphorylation. Functional proteomics can now be used to identify the phosphoproteome in general and specific kinase targets in particular. This approach is described along with findings to date. Key outstanding questions regarding the activation of the developmental program are framed in the context of what has been learned from the genome and how this knowledge can be applied to functional studies

AR2, a novel automatic muscle artifact reduction software method for ictal EEG interpretation: Validation and comparison of performance with commercially available software.

Objective: To develop a novel software method (AR2) for reducing muscle contamination of ictal scalp electroencephalogram (EEG), and validate this method on the basis of its performance in comparison to a commercially available software method (AR1) to accurately depict seizure-onset location. Methods: A blinded investigation used 23 EEG recordings of seizures from 8 patients. Each recording was uninterpretable with digital filtering because of muscle artifact and processed using AR1 and AR2 and reviewed by 26 EEG specialists. EEG readers assessed seizure-onset time, lateralization, and region, and specified confidence for each determination. The two methods were validated on the basis of the number of readers able to render assignments, confidence, the intra-class correlation (ICC), and agreement with other clinical findings. Results: Among the 23 seizures, two-thirds of the readers were able to delineate seizure-onset time in 10 of 23 using AR1, and 15 of 23 using AR2 (

Development of a mouse test for repetitive, restricted behaviors: Relevance to autism

Repetitive behavior, a core symptom of autism, encompasses stereotyped responses, restricted interests, and resistance to change. These studies investigated whether different components of the repetitive behavior domain could be modeled in the exploratory hole-board task in mice. Four inbred mouse strains, C57BL/6J, BALB/cByJ, BTBR T+tf/J, and FVB/NJ, and mice with reduced expression of Grin1, leading to NMDA receptor hypofunction (NR1neo/neo mice), were tested for exploration and preference for olfactory stimuli in an activity chamber with a 16-hole floor-board. Reduced exploration and high preference for holes located in the corners of the chamber were observed in BALB/cByJ and BTBR T+tf/J mice. All inbred strains had initial high preference for a familiar olfactory stimulus (clean cage bedding). BTBR T+tf/J was the only strain that did not demonstrate a shift in hole preference towards an appetitive olfactory stimulus (cereal or a chocolate chip), following home cage exposure to the food. The NR1neo/neo mice showed lower hole selectivity and aberrant olfactory stimulus preference, in comparison to wildtype controls. The results indicate that NR1neo/neo mice have repetitive nose poke responses that are less modified by environmental contingencies than responses in wildtype mice. 25-30% of NMDA-receptor hypomorphic mice also show self-injurious responses. Findings from the olfactory studies suggest that resistance to change and restricted interests might be modeled in mice by a failure to alter patterns of hole preference following familiarization with an appetitive stimulus, and by high preference persistently demonstrated for one particular olfactory stimulus. Further work is required to determine the characteristics of optimal mouse social stimuli in the olfactory hole-board test