A New American High School

This project is about the design of a secondary school for the community of Farmington, Minnesota and Independent School District 192. The site chosen for this project is near the current school placement so as to share existing amenities reducing impact on the site. As the population of Farmington is on the rise, the need for a secondary school is imminent. This thesis is a response to the challenge of meeting high standards of education with a building that successfully responds to the need for a healthy and supportive environment for its students and staff. The intention is to design a school that is small to mid-sized so that students can retain a sense of community and foster integrated learning

β1 integrin-extracellular matrix interactions are essential for maintaining exocrine pancreas architecture and function

Integrin receptors are responsible for integrating extracellular matrix signals inside the cell. The most prominent integrin receptor, β1 integrin, has a role in cell function, survival and differentiation. Recently, we demonstrated a profound in vivo role of β1 integrin expression in the pancreas on glucose homeostasis and islet function. Here, we extend these results by examining the role of β1 integrin in exocrine pancreatic structure and function. Adult C57Bl/6 mice hemizygous for a collagen type Iα2 (Col1a2) promoter-controlled tamoxifen-inducible Cre recombinase gene and homozygous for loxP-β1 integrin were injected with tamoxifen or corn oil to generate mice deleted or not for β1 integrin. Pancreata derived from these male mice were analyzed by quantitative reverse transcriptase-polymerase chain reaction, western blot and immunofluorescence. Our results showed that β1 integrin-deficient mice displayed a significant decrease in pancreas weight with a significant reduction of amylase, regenerating islet-derived protein II and carboxypeptidase-A expression (P\u3c0.05-0.01). Compared with control pancreata, β1 integrin-deficient pancreata showed reduced mRNA expression of extracellular matrix (collagen type Iα2, fibronectin and laminin) genes (P\u3c0.05), detached acini clusters and lost focal adhesion structure. Moreover, β1 integrin-deficient pancreatic acinar cells displayed decreased proliferation (P\u3c0.05) and increased apoptosis (P\u3c0.001). Apoptosis was reduced to that of controls when isolated exocrine clusters were cultured in media supplemented with extracellular matrix proteins. Taken together, these results implicate β1 integrin as an essential component for maintaining exocrine pancreatic structure and function. © 2013 USCAP, Inc All rights reserved

TRIDENT: an infrared camera optimized for the detection of methanated substellar companions around nearby stars

A near-infrared (0.85-2.5 microns) camera in use at the Canada-France-Hawaii Telescope and at the 1.6m telescope of the Observatoire du Mont-Megantic is described. The camera is based on a Hawaii-1 1024x1024 HgCdTe array detector. Its main feature is to acquire three simultaneous images at three wavelengths (simultaneous differential imaging) across the methane absorption bandhead at 1.6 micron, enabling an accurate subtraction of the stellar point spread function (PSF) and the detection of faint close methanated companions. The instrument has no coronagraph and features a fast (1 MHz) data acquisition system without reset anomaly, yielding high observing efficiencies on bright stars. The performance of the instrument is described, and it is illustrated by CFHT images of the nearby star Ups And. TRIDENT can detect (3 sigma) a methanated companion with DeltaH=10 at 0.5 arcsec from the star in one hour of observing time. Non-common path aberrations between the three optical paths are the limiting factors preventing further PSF attenuation. Reference star subtraction and instrument rotation improve the detection limit by one order of magnitude.Comment: 8 pages, 6 figures, to appear in SPIE 486

TRIDENT: an Infrared Differential Imaging Camera Optimized for the Detection of Methanated Substellar Companions

A near-infrared camera in use at the Canada-France-Hawaii Telescope (CFHT) and at the 1.6-m telescope of the Observatoire du Mont-Megantic is described. The camera is based on a Hawaii-1 1024x1024 HgCdTe array detector. Its main feature is to acquire three simultaneous images at three wavelengths across the methane absorption bandhead at 1.6 microns, enabling, in theory, an accurate subtraction of the stellar point spread function (PSF) and the detection of faint close methanated companions. The instrument has no coronagraph and features fast data acquisition, yielding high observing efficiency on bright stars. The performance of the instrument is described, and it is illustrated by laboratory tests and CFHT observations of the nearby stars GL526, Ups And and Chi And. TRIDENT can detect (6 sigma) a methanated companion with delta H = 9.5 at 0.5" separation from the star in one hour of observing time. Non-common path aberrations and amplitude modulation differences between the three optical paths are likely to be the limiting factors preventing further PSF attenuation. Instrument rotation and reference star subtraction improve the detection limit by a factor of 2 and 4 respectively. A PSF noise attenuation model is presented to estimate the non-common path wavefront difference effect on PSF subtraction performance.Comment: 41 pages, 16 figures, accepted for publication in PAS

Knockdown of Ant2 Reduces Adipocyte Hypoxia And Improves Insulin Resistance in Obesity.

Decreased adipose tissue oxygen tension and increased HIF-1α expression can trigger adipose tissue inflammation and dysfunction in obesity. Our current understanding of obesity-associated decreased adipose tissue oxygen tension is mainly focused on changes in oxygen supply and angiogenesis. Here, we demonstrate that increased adipocyte O2 demand, mediated by ANT2 activity, is the dominant cause of adipocyte hypoxia. Deletion of adipocyte Ant2 improves obesity-induced intracellular adipocyte hypoxia by decreasing obesity-induced adipocyte oxygen demand, without effects on mitochondrial number or mass, or oligomycin-sensitive respiration. This led to decreased adipose tissue HIF-1α expression and inflammation with improved glucose tolerance and insulin resistance in both a preventative or therapeutic setting. Our results suggest that ANT2 may be a target for the development of insulin sensitizing drugs and that ANT2 inhibition might have clinical utility

Microbiota-Produced N-Formyl Peptide fMLF Promotes Obesity-Induced Glucose Intolerance.

The composition of the gastrointestinal microbiota and associated metabolites changes dramatically with diet and the development of obesity. Although many correlations have been described, specific mechanistic links between these changes and glucose homeostasis remain to be defined. Here we show that blood and intestinal levels of the microbiota-produced N-formyl peptide, formyl-methionyl-leucyl-phenylalanine, are elevated in high-fat diet-induced obese mice. Genetic or pharmacological inhibition of the N-formyl peptide receptor Fpr1 leads to increased insulin levels and improved glucose tolerance, dependent upon glucagon-like peptide 1. Obese Fpr1 knockout mice also display an altered microbiome, exemplifying the dynamic relationship between host metabolism and microbiota. Overall, we describe a new mechanism by which the gut microbiota can modulate glucose metabolism, providing a potential approach for the treatment of metabolic disease

Search for residual prostate cancer on pT0 radical prostatectomy after positive biopsy

Reported incidence of no residual prostate cancer (i.e. pathological stage pT0) on radical prostatectomy ranges from 0.07 to 4.2%. The incidence is higher after neoadjuvant endocrine treatment. The aim of this study was to search for residual cancer on radical prostatectomy (RP) specimens when an initial sampling failed to find the cancer in patients with positive biopsy. Our database of 1,328 consecutive patients whose biopsies and RP specimen were both examined at the Polytechnic University-United Hospitals of the Marche Region between March 1995 and June 2006 was reviewed. The radical prostatectomies were grossly completely sampled and examined with the whole mount technique. We identified eight patients (i.e. 0.6%; three untreated and five hormonally treated preoperatively, i.e. 0.3 and 0.8%, respectively, of the total number of RPs included in the study) with positive biopsy and with no residual cancer in the initial routine histological examination of the RP. The RP of this group of eight was subjected to additional sectioning and evaluation of the paraffin blocks of the prostatectomy, also after block-flipping, immunostaining with an antibody against CAM 5.2, p63, PSA, and alpha-methylacyl-CoA racemase, and DNA specimen identity analysis. There were no cases with a false positive biopsy diagnosis, and cancer was not overlooked or missed in the initial routine histological examination of any of the 8 pT0 RPs. A minute focus of cancer (the diameter was always below 2.0 mm) was found on the additional sections in five. In particular, cancer was found after block-flipping in one of them. In an additional case, cancer was eventually discovered after immunostaining tissue sections for cytokeratin CAM 5.2, for p63 and PSA. In the remaining two cases (one untreated and the other hormonally treated), cancer was not found (0.15% of the 1,328 RPs included in the study); the review of the description of the macroscopic appearance of the RP and of its slides revealed that part of the peripheral zone corresponding to the site of the positive biopsy was missing, i.e. not removed from the patient at the time of the operation at least in one of the two. DNA specimen analysis confirmed the identity of the biopsy and prostatectomy in both. An extensive search for residual cancer reduces the number of pT0 RPs after a positive biopsy from 0.6 to 0.15%. It is recommended to have the needle biopsy reviewed, carefully look again at the radical prostatectomy, do deeper sections and then flip certain paraffin blocks. In addition, atypical foci should be stained for basal cell markers and often AMACR, especially in hormone-treated cases. If a block is missing part of the peripheral zone (capsular incision), this should be commented on. DNA analysis for tissue identity should be performed when the other steps have been taken without finding cancer