Chronic GLP-1 receptor activation by exendin-4 induces expansion of pancreatic duct glands in rats and accelerates formation of dysplastic lesions and chronic pancreatitis in the Kras(G12D) mouse model.

Pancreatic duct glands (PDGs) have been hypothesized to give rise to pancreatic intraepithelial neoplasia (PanIN). Treatment with the glucagon-like peptide (GLP)-1 analog, exendin-4, for 12 weeks induced the expansion of PDGs with mucinous metaplasia and columnar cell atypia resembling low-grade PanIN in rats. In the pancreata of Pdx1-Cre; LSL-Kras(G12D) mice, exendin-4 led to acceleration of the disruption of exocrine architecture and chronic pancreatitis with mucinous metaplasia and increased formation of murine PanIN lesions. PDGs and PanIN lesions in rodent and human pancreata express the GLP-1 receptor. Exendin-4 induced proproliferative signaling pathways in human pancreatic duct cells, cAMP-protein kinase A and mitogen-activated protein kinase phosphorylation of cAMP-responsive element-binding protein, and increased cyclin D1 expression. These GLP-1 effects were more pronounced in the presence of an activating mutation of Kras and were inhibited by metformin. These data reveal that GLP-1 mimetic therapy may induce focal proliferation in the exocrine pancreas and, in the context of exocrine dysplasia, may accelerate formation of neoplastic PanIN lesions and exacerbate chronic pancreatitis

A rectangular waveguide cell for measurement of the shielding effectiveness of anisotropic materials

A method for measuring the shielding effectiveness of planar anisotropic materials using a rectangular waveguide cell is proposed. Computational models are used to verify the behaviour of the cell and validate its ability to measure shielding effectiveness. Results of measurements on a control sample and three carbon-fibre composite laminates in a GTEM cell are presented. A dynamic range of 70 dB with a capability to discriminate 20 dB of anisotropy is achieved in the frequency range 400-1600 MHz using cubic cells of side length 200 mm and 300 mm

Marked expansion of exocrine and endocrine pancreas with incretin therapy in humans with increased exocrine pancreas dysplasia and the potential for glucagon-producing neuroendocrine tumors.

Controversy exists regarding the potential regenerative influences of incretin therapy on pancreatic β-cells versus possible adverse pancreatic proliferative effects. Examination of pancreata from age-matched organ donors with type 2 diabetes mellitus (DM) treated by incretin therapy (n = 8) or other therapy (n = 12) and nondiabetic control subjects (n = 14) reveals an ∼40% increased pancreatic mass in DM treated with incretin therapy, with both increased exocrine cell proliferation (P < 0.0001) and dysplasia (increased pancreatic intraepithelial neoplasia, P < 0.01). Pancreata in DM treated with incretin therapy were notable for α-cell hyperplasia and glucagon-expressing microadenomas (3 of 8) and a neuroendocrine tumor. β-Cell mass was reduced by ∼60% in those with DM, yet a sixfold increase was observed in incretin-treated subjects, although DM persisted. Endocrine cells costaining for insulin and glucagon were increased in DM compared with non-DM control subjects (P < 0.05) and markedly further increased by incretin therapy (P < 0.05). In conclusion, incretin therapy in humans resulted in a marked expansion of the exocrine and endocrine pancreatic compartments, the former being accompanied by increased proliferation and dysplasia and the latter by α-cell hyperplasia with the potential for evolution into neuroendocrine tumors

Quantification of Bronchial Circulation Perfusion in Rats

The bronchial circulation is thought to be the primary blood supply for pulmonary carcinomas. Thus, we have developed a method for imaging and quantifying changes in perfusion in the rat lung due to development of the bronchial circulation. A dual-modality micro-CT/SPECT system was used to detect change in perfusion in two groups of rats: controls and those with a surgically occluded left pulmonary artery. Both groups were imaged following injections on separate days i) 2mCi of Tc99m labeled macroaggregated albumin (MAA) into the left carotid artery (IA) and ii) a similar injection into the femoral vein (IV). The IA injection resulted in Tc99m accumulation in capillaries of the systemic circulation including the bronchial circulation, whereas the IV resulted in Tc99m accumulation in the pulmonary capillaries. Ordered subset expectation maximization (OSEM) was used to reconstruct the SPECT image volumes and a Feldkamp algorithm was used to reconstruct the micro-CT image volumes. The micro-CT and SPECT volumes were registered, the SPECT image volume was segmented using the right and left lung boundaries defined from the micro-CT volume, and the ratio of IA radioactivity accumulation in the left lung to IV radioactivity accumulation in both lungs was used as a measure of left lung flow via the bronchial circulation. This ratio was ~0.02 for the untreated rats compared to the treated animals that had an increased flow ratio of ~0.21 40 days after left pulmonary artery occlusion. This increase in flow to the occluded left lung via the bronchial circulation suggests this will be a useful model for further investigating antiangiogenic treatments

Quantification of Bronchial Circulation Perfusion in Rats

The bronchial circulation is thought to be the primary blood supply for pulmonary carcinomas. Thus, we have developed a method for imaging and quantifying changes in perfusion in the rat lung due to development of the bronchial circulation. A dual-modality micro-CT/SPECT system was used to detect change in perfusion in two groups of rats: controls and those with a surgically occluded left pulmonary artery. Both groups were imaged following injections on separate days i) 2mCi of Tc99m labeled macroaggregated albumin (MAA) into the left carotid artery (IA) and ii) a similar injection into the femoral vein (IV). The IA injection resulted in Tc99m accumulation in capillaries of the systemic circulation including the bronchial circulation, whereas the IV resulted in Tc99m accumulation in the pulmonary capillaries. Ordered subset expectation maximization (OSEM) was used to reconstruct the SPECT image volumes and a Feldkamp algorithm was used to reconstruct the micro-CT image volumes. The micro-CT and SPECT volumes were registered, the SPECT image volume was segmented using the right and left lung boundaries defined from the micro-CT volume, and the ratio of IA radioactivity accumulation in the left lung to IV radioactivity accumulation in both lungs was used as a measure of left lung flow via the bronchial circulation. This ratio was ~0.02 for the untreated rats compared to the treated animals that had an increased flow ratio of ~0.21 40 days after left pulmonary artery occlusion. This increase in flow to the occluded left lung via the bronchial circulation suggests this will be a useful model for further investigating antiangiogenic treatments

Exploring heritage through time and space : Supporting community reflection on the highland clearances

On the two hundredth anniversary of the Kildonan clearances, when people were forcibly removed from their homes, the Timespan Heritage centre has created a program of community centred work aimed at challenging pre conceptions and encouraging reflection on this important historical process. This paper explores the innovative ways in which virtual world technology has facilitated community engagement, enhanced visualisation and encouraged reflection as part of this program. An installation where users navigate through a reconstruction of pre clearance Caen township is controlled through natural gestures and presented on a 300 inch six megapixel screen. This environment allows users to experience the past in new ways. The platform has value as an effective way for an educator, artist or hobbyist to create large scale virtual environments using off the shelf hardware and open source software. The result is an exhibit that also serves as a platform for experimentation into innovative ways of community co-creation and co-curation.Postprin

Characteristics of GaInNAsSb VCSELs operating near 1.55µm

A detailed study of the high-power pulsed operation of C-band optically-pumped GaInNAsSb vertical cavity surface emitting lasers is reported. The devices employ a resonant periodic gain structure grown by molecular beam epitaxy on a GaAs substrate with a 31-pair GaAs/AlAs bottom distributed Bragg reflector and a 4-λ, GaAs-based resonant cavity containing 10 GaInNAsSb quantum wells distributed among the 7 antinodes of the electric field. A dual-pump-band SiO2/TiO2 dielectric top mirror allows efficient optical pumping via low reflectivities at 808nm and 1064nm while providing very high reflectivity at the 1.55μm target emission wavelength. The laser characteristics were evaluated using both a Q-switched Nd:YAG 1064nm pump and a 20W-peak 180ns-pulsed 850nm diode laser. The importance of the gain-cavity detuning was evident from time-dependent spectral measurements of laser material subjected to post-growth annealing at different temperatures between 725 and 775°C. The highest annealing temperature produces the largest blue shift of the gain peak relative to the cavity resonance, resulting in the best power transfer characteristics as well as reduced temperature sensitivity

MC2^2: Subaru and Hubble Space Telescope Weak-Lensing Analysis of the Double Radio Relic Galaxy Cluster PLCK G287.0+32.9

The second most significant detection of the Planck Sunyaev Zel'dovich survey, PLCK~G287.0+32.9 ($z=0.385$) boasts two similarly bright radio relics and a radio halo. One radio relic is located $\sim 400$ kpc northwest of the X-ray peak and the other $\sim 2.8$ Mpc to the southeast. This large difference suggests that a complex merging scenario is required. A key missing puzzle for the merging scenario reconstruction is the underlying dark matter distribution in high resolution. We present a joint Subaru Telescope and {\it Hubble Space Telescope} weak-lensing analysis of the cluster. Our analysis shows that the mass distribution features four significant substructures. Of the substructures, a primary cluster of mass $M_{200\text{c}}=1.59^{+0.25}_{-0.22}\times 10^{15} \ h^{-1}_{70} \ \text{M}_{\odot}$dominates the weak-lensing signal. This cluster is likely to be undergoing a merger with one (or more) subcluster whose mass is approximately a factor of 10 lower. One candidate is the subcluster of mass$M_{200\text{c}}=1.16^{+0.15}_{-0.13}\times 10^{14} \ h^{-1}_{70} \ \text{M}_{\odot}$located$\sim 400$kpc to the southeast. The location of this subcluster suggests that its interaction with the primary cluster could be the source of the NW radio relic. Another subcluster is detected$\sim 2$Mpc to the SE of the X-ray peak with mass$M_{200\text{c}}=1.68^{+0.22}_{-0.20}\times 10^{14} \ h^{-1}_{70} \ \text{M}_{\odot}$. This SE subcluster is in the vicinity of the SE radio relic and may have created the SE radio relic during a past merger with the primary cluster. The fourth subcluster,$M_{200\text{c}}=1.87^{+0.24}_{-0.22}\times 10^{14} \ h^{-1}_{70} \ \text{M}_{\odot}$, is northwest of the X-ray peak and beyond the NW radio relic.Comment: 19 pages, 14 figures; Accepted to Ap