Creation of a Pioneer-Neuron Axonal Pathfinding Model for Future Applications in Developmental Neurotoxicity Testing

The developing central nervous system is a unique target for environmental toxicants both pre- and postnatal. Exposure to industrial chemical toxicants at various stages throughout development are known to contribute to injuries that result in autism, attention-deficit hyperactivity disorder (ADHD), dyslexia, and other cognitive impairments [81]. The damage caused by these exposures is often untreatable and frequently permanent, resulting in reduced intelligence (expressed in terms of lost IQ points) or behavioral abnormalities. It is now reported that 10-15% of all births are associated with disorders of neurobehavioral development [81], where 1 in 68 children in the United States is diagnosed with some form of an autism spectrum disorder (ASD) [7, 93, 188] and 14% of the roughly 4 million children born each year suffer from ADHD [124]. It is estimated that 3% of developmental disabilities are the direct result of environmental exposure, and that another 25% stem from interactions between environmental factors and genetic susceptibility [80, 146]. With more diagnosed cases and rising costs, the identification of the chemicals responsible for the deleterious effects on the developing nervous system has become significant topic of research. Current developmental neurotoxicity (DNT) testing relies heavily on whole animal approaches for hazard identification and dose-response evaluations. These methods are not practical for screening the over 82,000 chemicals already used in commerce with an additional 700 new chemicals introduced annually [24]. Following the first workshop on “Incorporating In Vitro Alternative Methods for Developmental Neurotoxicity (DNT) Testing into International Hazard and Risk Assessment Strategies†in 2005, it was determined that in vitro DNT testing methods should be included as part of a tiered approach to help create a reference list of potential developmentally neurotoxic chemicals and catalog the effects they have on various developmental mechanistic endpoints [40, 127]. Using directionality of pioneer-neuron axonal pathfinding as the mechanism for evaluation, we developed a biochip-based single-neuron axonal pathfinding assay to subjugate extending axons to simultaneous geometric and chemical guidance. To achieve this we devised a laser cell-micropatterning system to facilitate the placement of individual-neurons to exact locations on a PDMS substrate. The cell-culture conditions were optimized to promote single-neuron axonal extension through and beyond the confinements of a geometric guidance microchannel. Evaluation of the pathfinding direction in response to geometric guidance was compared to that of geometric and chemical stimuli. We found using our system that the addition of a chemical guidance component 1) increased the number of individual-neurons extending an axon at least 20 µm beyond the end of a guidance microchannel structure and 2) showed the potential to elicit a growth cone turning event by abruptly changing the initial pathfinding trajectory of an axon. Based on our previous study that single-neuron axonal pathfinding under geometric guidance is one order of magnitude more sensitive to a chemical toxicant, our research data demonstrate that we have created a platform that can be used to test the possible effects that low dose (nM concentrations) chemical exposures may have on pioneer-neuron axonal pathfinding

Measurement-Based Quantum Thermal Machines with Feedback Control

We investigated coupled-qubit-based thermal machines powered by quantum measurements and feedback. We considered two different versions of the machine: (1) a quantum Maxwell’s demon, where the coupled-qubit system is connected to a detachable single shared bath, and (2) a measurement-assisted refrigerator, where the coupled-qubit system is in contact with a hot and cold bath. In the quantum Maxwell’s demon case, we discuss both discrete and continuous measurements. We found that the power output from a single qubit-based device can be improved by coupling it to the second qubit. We further found that the simultaneous measurement of both qubits can produce higher net heat extraction compared to two setups operated in parallel where only single-qubit measurements are performed. In the refrigerator case, we used continuous measurement and unitary operations to power the coupled-qubit-based refrigerator. We found that the cooling power of a refrigerator operated with swap operations can be enhanced by performing suitable measurements

Primary Dendrite Array: Observations from Ground-Based and Space Station Processed Samples

Influence of natural convection on primary dendrite array morphology during directional solidification is being investigated under a collaborative European Space Agency-NASA joint research program, Microstructure Formation in Castings of Technical Alloys under Diffusive and Magnetically Controlled Convective Conditions (MICAST). Two Aluminum-7 wt pct Silicon alloy samples, MICAST6 and MICAST7, were directionally solidified in microgravity on the International Space Station. Terrestrially grown dendritic monocrystal cylindrical samples were remelted and directionally solidified at 18 K per centimeter (MICAST6) and 28 K per centimeter (MICAST7). Directional solidification involved a growth speed step increase (MICAST6-from 5 to 50 millimeters per second) and a speed decrease (MICAST7-from 20 to 10 millimeters per second). Distribution and morphology of primary dendrites is currently being characterized in these samples, and also in samples solidified on earth under nominally similar thermal gradients and growth speeds. Primary dendrite spacing and trunk diameter measurements from this investigation will be presented

Recycling Lingware in a Multilingual MT System

We describe two methods relevant to multi-lingual machine translation systems, which can be used to port linguistic data (grammars, lexicons and transfer rules) between systems used for processing related languages. The methods are fully implemented within the Spoken Language Translator system, and were used to create versions of the system for two new language pairs using only a month of expert effort.Comment: 6 pages, needs aclap.sty. To appear in "From Research to Commercial Applications" workshop at ACL-97, see also http://www.cam.sri.co

Estimates of Harvest Potential and Distribution of the Deep Sea Red Crab, Chaceon quinquedens, in the North Central Gulf of Mexico

Harvest potential, relative abundance, and geographic and bathymetric distribution are discussed for the red crab, Chaceon quinquedens, in the northcentral Gulf of Mexico. Harvest potential is expressed as the number of trapable crabs present on fishing grounds defined as depths ranging from 677 m to 1043 m between 87.5o and 88.5oW longitude. Using various estimates of the effective fishing area (EFA) of a trap, the number of trapable red crabs on the fishing grounds ranged from 3.7 x 106 to 10.7 x 106. Estimatesofcrabnumberssuggest there is a potential for commercial harvest in the northcentral Gulf of Mexico, east of the Mississippi River. However, fishery development must take into consideration the preponderance of females on the defined fishing grounds (MF ratio = 1:2.1) and the high incidence of ovigerous females (~20%) during much of the year. Females generally dominated at all depth strata, but the proportion of males to females increased with depth. Reduced numbers of red crabs were collected off the western Louisiana coast and a shift in depth distribution was found. Minimum upper depth limit for red crabs west of the Mississippi River was 860 m as compared to 677 m east of the River. The known range of C. fenneri is extended to 92o12 W longitude

Estimates of Harvest Potential and Distribution of the Deep Sea Red Crab, Chaceon quinquedens, in the North Central Gulf of Mexico

Harvest potential, relative abundance, and geographic and bathymetric distribution are discussed for the red crab, Chaceon quinquedens, in the northcentral Gulf of Mexico. Harvest potential is expressed as the number of trapable crabs present on fishing grounds defined as depths ranging from 677 m to 1043 m between 87.5o and 88.5oW longitude. Using various estimates of the effective fishing area (EFA) of a trap, the number of trapable red crabs on the fishing grounds ranged from 3.7 x 106 to 10.7 x 106. Estimatesofcrabnumberssuggest there is a potential for commercial harvest in the northcentral Gulf of Mexico, east of the Mississippi River. However, fishery development must take into consideration the preponderance of females on the defined fishing grounds (MF ratio = 1:2.1) and the high incidence of ovigerous females (~20%) during much of the year. Females generally dominated at all depth strata, but the proportion of males to females increased with depth. Reduced numbers of red crabs were collected off the western Louisiana coast and a shift in depth distribution was found. Minimum upper depth limit for red crabs west of the Mississippi River was 860 m as compared to 677 m east of the River. The known range of C. fenneri is extended to 92o12 W longitude

Occurrence of Chaceon Larvae in Plankton Samples from Slope Waters of the Northeastern Gulf of Mexico

Geographic, seasonal, and bathymetric distributions of Chaceon larvae are described for the northeastern Gulf of Mexico

Occurrence of Chaceon Larvae in Plankton Samples from Slope Waters of the Northeastern Gulf of Mexico

Geographic, seasonal, and bathymetric distributions of Chaceon larvae are described for the northeastern Gulf of Mexico

Aristaless-like homeobox protein 1 (ALX1) variant associated with craniofacial structure and frontonasal dysplasia in Burmese cats

AbstractFrontonasal dysplasia (FND) can have severe presentations that are medically and socially debilitating. Several genes are implicated in FND conditions, including Aristaless-Like Homeobox 1 (ALX1), which is associated with FND3. Breeds of cats are selected and bred for extremes in craniofacial morphologies. In particular, a lineage of Burmese cats with severe brachycephyla is extremely popular and is termed Contemporary Burmese. Genetic studies demonstrated that the brachycephyla of the Contemporary Burmese is a simple co-dominant trait, however, the homozygous cats have a severe craniofacial defect that is incompatible with life. The craniofacial defect of the Burmese was genetically analyzed over a 20 year period, using various genetic analysis techniques. Family-based linkage analysis localized the trait to cat chromosome B4. Genome-wide association studies and other genetic analyses of SNP data refined a critical region. Sequence analysis identified a 12bp in frame deletion in ALX1, c.496delCTCTCAGGACTG, which is 100% concordant with the craniofacial defect and not found in cats not related to the Contemporary Burmese

Immunohistochemical Analysis of the Natural Killer Cell Cytotoxicity Pathway in Human Abdominal Aortic Aneurysms

Our previous analysis using genome-wide microarray expression data revealed extreme overrepresentation of immune related genes belonging the Natural Killer (NK) Cell Mediated Cytotoxicity pathway (hsa04650) in human abdominal aortic aneurysm (AAA). We followed up the microarray studies by immunohistochemical analyses using antibodies against nine members of the NK pathway (VAV1, VAV3, PLCG1, PLCG2, HCST, TYROBP, PTK2B, TNFA, and GZMB) and aortic tissue samples from AAA repair operations (n = 6) and control aortae (n = 8) from age-, sex- and ethnicity-matched donors from autopsies. The results confirmed the microarray results. Two different members of the NK pathway, HCST and GRZB, which act at different steps in the NK-pathway, were actively transcribed and translated into proteins in the same cells in the AAA tissue demonstrated by double staining. Furthermore, double staining with antibodies against CD68 or CD8 together with HCST, TYROBP, PTK2B or PLCG2 revealed that CD68 and CD8 positive cells expressed proteins of the NK-pathway but were not the only inflammatory cells involved in the NK-pathway in the AAA tissue. The results provide strong evidence that the NK Cell Mediated Cytotoxicity Pathway is activated in human AAA and valuable insight for future studies to dissect the pathogenesis of human AAA