Increased Stem Cell Factor Release by Hemangioma-Derived Endothelial Cells

Background: Capillary hemangiomas, the most common tumors in young children, consist of proliferating capillary vessels and endothelial cells. These tumors also contain large numbers of mast cells, compared with the normal surrounding skin or tissue. We have recently shown that stem cell factor (SCF), the gene product of the murine steel locus, can act as a chemoattractant for mast cells. In this study, we investigated whether SCF might be involved in the recruitment and maintenance of mast cells in hemangiomas. Experimental Design: Cultured endothelial cells derived from a murine hemangioma were compared with normal vascular endothelial cells for the ability to produce and release SCF, a mitogen for mast cells. Results: Conditioned medium from hemangioma-derived endothelial cells stimulated the proliferation of cultured mast cells. This proliferative activity was potentiated by interleukin-3. The same conditioned medium was unable to stimulate proliferation of mast cells expressing a defective receptor for SCF. The medium was also unable to stimulate proliferation when it was preincubated with neutralizing antibodies specific for SCF. Immunoprecipitation and Western blot analysis of the conditioned media from hemangioma cells and normal endothelial cells demonstrated the 31,000 molecular weight SCF in hemangioma-conditioned medium only. In addition, proliferative activity for mast cells could not be demonstrated in the conditioned medium of the normal endothelial cells, although Northern blot analysis indicated that both normal and hemangioma-derived endothelial cells express SCF mRNA. Reverse transcriptase-polymerase chain reaction techniques were used to amplify the DNA sequence coding for the proteolytic cleavage site used for release of SCF. Results indicated that both normal and hemangioma-derived endothelial cells express the same transcript for SCF. Conclusions: Our data suggest that increased release of SCF is a property of hemangioma-derived endothelial cells that may account for the high numbers of mast cells observed in hemangioma tissue. This increased release of SCF is not due to alternate splicing of SCF transcripts by hemangioma cells

Identification of Six Novel SOD1 Gene Mutations in Familial Amyotrophic Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the premature death of motor neurons. In approximately 10% of the cases the disease is inherited as autosomal dominant trait (FALS). It has been found that mutations in the Cu/Zn superoxide dismutase gene (SODl) are responsible for approximately 15% of FALS kindreds. We screened affected individuals from 70 unrelated FALS kindreds and identified 10 mutations, 6 of which are novel. Surprisingly, we have found a mutation in exon 3, which includes most of the active site loop and Zn2+ binding sites, a region where no previous SOD1 mutations have been found. Our data increase the number of different SODl mutations causing FALS to 55, a significant fraction of the 154 amino acids of this relatively small protei

Bed conduction impact on fiber optic distributed temperature sensing water temperature measurements

Error in distributed temperature sensing (DTS) water temperature measurements may be introduced by contact of the fiber optic cable sensor with bed materials (e.g., seafloor, lakebed, streambed). Heat conduction from the bed materials can affect cable temperature and the resulting DTS measurements. In the Middle Fork John Day River, apparent water temperature measurements were influenced by cable sensor contact with aquatic vegetation and fine sediment bed materials. Affected cable segments measured a diurnal temperature range reduced by 10%and lagged by 20–40 min relative to that of ambient stream temperature. The diurnal temperature range deeper within the vegetation–sediment bed material was reduced 70% and lagged 240 min relative to ambient stream temperature. These site-specific results illustrate the potential magnitude of bed-conduction impacts with buried DTS measurements. Researchers who deploy DTS for water temperature monitoring should understand the importance of the environment into which the cable is placed on the range and phase of temperature measurements.This is the publisher’s final pdf. The published article is copyrighted by the author(s) and published by Copernicus Publications on behalf of the European Geosciences Union. The published article can be found at: http://www.geoscientific-instrumentation-methods-and-data-systems.net

SYSTEMS ANALYSIS OF ARMY MATERIEL REPORTING FOR THE MIDDLE TIER OF ACQUISITION PATHWAY

The Acquisition Modernization Integration (AMI) team within the ASA(ALT) office is critical in the Army decision-making process. The AMI creates reports that include actionable knowledge rendered to Army strategic leaders. These reports include vital data on critical Army programs integrated into the modernization efforts. Part of this necessary data are the First Unit Issued (FUI) and the First Unit Equipped (FUE) dates. These reported dates directly affect Army units’ training, deployment, and logistics support timelines as they become part of the data-driven analytics on reports provided to decision-makers. Because of the initiatives to improve efficiency in the acquisition process, realignment, and creation of new organizations, the AMI needs a system that facilitates accurate and consistent FUI and FUE dates reporting. This research used several systems engineering (SE) concepts and methods such as stakeholders’ analysis, functional analysis, mapping of functions to systems’ parameters, modeling-based systems engineering, and analysis of alternatives. The application of these SE tools resulted in identifying a system/process that will accurately and consistently facilitate FUI and FUE date reporting to meet the AMI’s needs. This system/process provides a reporting capability for current and future acquisition programs and could be implemented across the DOD and all other government agencies and departments.Major, United States ArmyCaptain, United States ArmyCaptain, United States ArmyCaptain, United States ArmyCaptain, United States ArmyApproved for public release. Distribution is unlimited

Technical Note: Bed conduction impact on fiber optic DTS water temperature measurements

Error in Distributed Temperature Sensor (DTS) water temperature measurements may be introduced by contact of the fiber optic cable sensor with bed materials (e.g., seafloor, lakebed, stream bed). Heat conduction from the bed materials can affect cable temperature and the resulting DTS measurements. In the Middle Fork John Day River, apparent water temperature measurements were influenced by cable sensor contact with aquatic vegetation and fine sediment bed materials. Affected cable segments measured a diurnal temperature range reduced by 10% and lagged by 20–40 min relative to that of ambient stream temperature. The diurnal temperature range deeper within the vegetation–sediment bed material was reduced 70% and lagged 240min relative to ambient stream temperature. These site-specific results illustrate the potential magnitude of bed-conduction impacts with buried DTS measurements. Researchers who deploy DTS for water temperature monitoring should understand the importance of the environment into which the cable is placed on the range and phase of temperature measurements.This discussion paper has been under review for the journal Geoscientific Instrumentation, Methods and Data Systems (GI). Please refer to the corresponding final paper in GI. The published article is copyrighted by the author(s) and published by Copernicus Publications on behalf of the European Geosciences Union. The published article can be found at: http://www.geoscientific-instrumentation-methods-and-data-systems.net/ The final revised paper is available at: http://hdl.handle.net/1957/5657

Gastrin Induces Nuclear Export and Proteasomal Degradation of Menin in Enteric Glial Cells

Background & aims: The multiple endocrine neoplasia, type 1 (MEN1) locus encodes the nuclear protein and tumor suppressor menin. MEN1 mutations frequently cause neuroendocrine tumors such as gastrinomas, characterized by their predominant duodenal location and local metastasis at time of diagnosis. Diffuse gastrin cell hyperplasia precedes the appearance of MEN1 gastrinomas, which develop within submucosal Brunner\u27s glands. We investigated how menin regulates expression of the gastrin gene and induces generation of submucosal gastrin-expressing cell hyperplasia. Methods: Primary enteric glial cultures were generated from the VillinCre:Men1FL/FL:Sst-/- mice or C57BL/6 mice (controls), with or without inhibition of gastric acid by omeprazole. Primary enteric glial cells from C57BL/6 mice were incubated with gastrin and separated into nuclear and cytoplasmic fractions. Cells were incubated with forskolin and H89 to activate or inhibit protein kinase A (a family of enzymes whose activity depends on cellular levels of cyclic AMP). Gastrin was measured in blood, tissue, and cell cultures using an ELISA. Immunoprecipitation with menin or ubiquitin was used to demonstrate post-translational modification of menin. Primary glial cells were incubated with leptomycin b and MG132 to block nuclear export and proteasome activity, respectively. We obtained human duodenal, lymph node, and pancreatic gastrinoma samples, collected from patients who underwent surgery from 1996 through 2007 in the United States or the United Kingdom. Results: Enteric glial cells that stained positive for glial fibrillary acidic protein (GFAP+) expressed gastrin de novo through a mechanism that required PKA. Gastrin-induced nuclear export of menin via cholecystokinin B receptor (CCKBR)-mediated activation of PKA. Once exported from the nucleus, menin was ubiquitinated and degraded by the proteasome. GFAP and other markers of enteric glial cells (eg, p75 and S100B), colocalized with gastrin in human duodenal gastrinomas. Conclusions: MEN1-associated gastrinomas, which develop in the submucosa, might arise from enteric glial cells through hormone-dependent PKA signaling. This pathway disrupts nuclear menin function, leading to hypergastrinemia and associated sequelae

Low-Cycle Fatigue of Ultra-Fine-Grained Cryomilled 5083 Aluminum Alloy

The cyclic deformation behavior of cryomilled (CM) AA5083 alloys was compared to that of conventional AA5083-H131. The materials studied were a 100 pct CM alloy with a Gaussian grain size average of 315 nm and an alloy created by mixing 85 pct CM powder with 15 pct unmilled powder before consolidation to fabricate a plate with a bimodal grain size distribution with peak averages at 240 nm and 1.8 μm. Although the ultra-fine-grain (UFG) alloys exhibited considerably higher tensile strengths than those of the conventional material, the results from plastic-strain-controlled low-cycle fatigue tests demonstrate that all three materials exhibit identical fatigue lives across a range of plastic strain amplitudes. The CM materials exhibited softening during the first cycle, similar to other alloys produced by conventional powder metallurgy, followed by continual hardening to saturation before failure. The results reported in this study show that fatigue deformation in the CM material is accompanied by slight grain growth, pinning of dislocations at the grain boundaries, and grain rotation to produce macroscopic slip bands that localize strain, creating a single dominant fatigue crack. In contrast, the conventional alloy exhibits a cell structure and more diffuse fatigue damage accumulation