Reduced skin tumor development in cyclin D1-deficient mice highlights the oncogenic ras pathway in vivo

Cyclin D1 is part of a cell cycle control node consistently deregulated in most human cancers. However, studies with cyclin D1-null mice indicate that it is dispensable for normal mouse development as well as cell growth in culture. Here, we provide evidence that ras-mediated tumorigenesis depends on signaling pathways that act preferentially through cyclin D1. Cyclin D1 expression and the activity of its associated kinase are up-regulated in keratinocytes in response to oncogenic ras. Furthermore, cyclin D1 deficiency results in up to an 80% decrease in the development of squamous tumors generated through either grafting of retroviral ras-transduced keratinocytes, phorbol ester treatment of ras transgenic mice, or two-stage carcinogenesis.     

Apolipoprotein E*3-Leiden transgenic mice as a test model for hypolipidaemic drugs

PURPOSE: We report an investigation into the distribution of proteoglycans (PGs) in normal, organ-cultured and dextran-treated human corneas. METHODS: Immunogold labeling was carried out at the electron microscope level to localize keratan sulphate (KS), chondroitin sulphate (CS), and heparan sulphate (HS) PGs. RESULTS: High levels of labeling for CS was found in the epithelium, endothelium, and keratocytes, with light labelling present in the basement membranes and the corneal stroma. Labeling for HS was present in the epithelium, endothelium, and keratocytes, with intense labeling present at the endothelium/Descemet's membrane interface and the epithelium/Bowman's layer interface. Large filaments were also observed in these regions in cuprolinic blue-stained specimens. Keratan sulphate was present at high levels in the stroma and the basement membranes with low levels present within the keratocytes, epithelium, and endothelium. The pattern of KS labeling along the collagen fibrils in the stroma sometimes showed evidence of periodicity. Organ-cultured corneas had extensive collagen-free "lakes," the interior of which immunolabeled positively for KS and showed staining with cuprolinic blue. The lakes were greatly reduced in the dextran-treated samples. CONCLUSION: This investigation determined the ultrastructural distribution of KS, CS, and HS PGs in human cornea and showed that organ culture is associated with a change in distribution of stromal PGs.     

Interference-based micromechanical spectral equalizers

Dynamic gain equalization filters (DGEFs) are important for high-performance wavelength division multiplexed (WDM) communications. One of the first demonstrated DGEF used a micromechanical etalon filter array illuminated with free-space spectral demultiplexing optics. Here, we present subsequent research on etalon-based dynamic spectral filters, including vertical device structures which linearize and reduce the drive voltage from 70 to 40 V, and spatially-segmented etalons which allow channelized spectral equalization and further reduce drive voltage. We describe a prototype using a simplified cylindrical optomechanical package with a 104-nm broadband spectral response, 7.5-dB insertion loss and less than 16-V operation voltage. Finally, we show the use of a 42-nm bandwidth DGEF prototype with feedback stabilization to more than double the number of channels and operating bandwidth of a conventional Erbium-doped fiber amplifier while maintaining < 1-dB power uniformity.     

The commercial currency of construction framework agreements

A critique is presented of construction client–main contractor framework agreements. In the midst of an unpredictable and volatile construction environment, the commercial currency of collaborative working practice, and by extension framework agreements, is being put under increasing management scrutiny. Drawing on a literature review, the guiding principles of framework agreements are examined. A dramatic downturn in construction demand has created considerable surplus in supply. Under such conditions the buyer–supplier interdependencies become imbalanced and commercial relationships fraught. Reports by construction industry analysts demonstrate a number of private sector clients rejecting framework agreements in favour of traditional competitive procurement practices. Drawing upon a neoclassical lens, three guiding principles embedded within economic orthodoxy are employed to examine business-to-business tensions within construction framework agreements, namely, individualism, instrumentalism and equilibrium. This neoclassical interpretation of construction framework agreements reveals a potential relational management bias within mainstream rhetoric. Notably, providing a complementary account of framework agreements practice should not be construed as a rejection of collaborative working practices. An alternative account of framework agreements is presented that does not rely upon the mainstream behavioural model of contemporary contracting.     

MODELLING OF MICROSTRUCTURE EVOLUTION AND PROPERTIES OF LOW-CARBON STEELS

1.IntroductionMicrostructureprocessmodelsareincreasinglyonhotstriprollingofste.l[1--7].Thesemodelsfrequentlyincorporateagreatdealofempiricismwithcomparativelytightprocessrangesofapplicability.Morefundamentallybasedprocessmodelsarerequiredtodeveloppredictivetoolstooptimizetheproductionforawiderangeofmilldesignsandprocessingconditions.Theprocessofhotstriprollingoflow--carbonsteelscanbesubdividedintothreeprin-cipalstages:(i)reheating,(n)rollingand(iii)cooling(watercoolingontherun--outtableandsubs…     

Cultural factors related to the peer review of teaching

Since 1994, the American Association for Higher Education Peer Review of Teaching Project has sought to popularize the notion that teaching is both a scholarly activity and community property to be shared with and critiqued by the larger academic community. In order to accomplish these goals, each of the three academic units at the twelve participating universities developed a pilot project that conformed to its own institutional, academic unit, and disciplinary culture. At a large Midwestern university, the academic units of mathematics, history, and nursing developed different projects. Each of these projects took account of the unit's specific culture, and this fact helps to account, in large part, for each project's success.     

Comparison of left anterior oblique, anterior, and geometric mean methods in gastric emptying assessment of postpancreaticoduodenectomy patients

Although left anterior oblique (LAO) gastric emptying studies appear to be an adequate alternative to geometric mean (GM) measurements in patients with normal gastric anatomy, it is not clear whether they can be used after gastric or duodenal surgery. In this study, dual-phase gastric emptying studies with combined solid-liquid meal were performed in 54 patients who had undergone pancreaticoduodenectomy (Whipple procedure). Gastric emptying was studied with GM, LAO, and anterior (ANT) methods. T1/2 and percent gastric retention at 10, 30, 60, 90, and 120 minutes were calculated. Results from the three methods were compared using correlation analysis and the t test. The t test showed no significant difference in T1/2 and percent retention values between the GM and LAO or ANT views. The solid emptying T1/2 showed a better correlation between GM and LAO values (r = 0.824) than between GM and ANT (r = 0.589). For the liquid T1/2, the reverse was true. Correlation between GM and ANT (r = 0.939) was better than between GM and LAO (r = 0.839); however, both LAO and ANT views correlated well with GM liquid emptying. It is concluded that the LAO view can replace GM gastric emptying methods in postpancreaticoduodenectomy patients for evaluation of both solid and liquid emptying, although the ANT view appears completely adequate for the study of liquid emptying.     

Molecular beam epitaxial HgCdTe material characteristics and device performance: Reproducibility status

Extensive material, device, and focal plane array (FPA) reproducibility data are presented to demonstrate significant advances made in the molecular beam epitaxial (MBE) HgCdTe technology. Excellent control of the composition, growth rate, layer thickness, doping concentration, dislocation density, and transport characteristics has been demonstrated. A change in the bandgap is readily achieved by adjusting the beam fluxes, demonstrating the flexibility of MBE in responding to the needs of infrared detection applications in various spectral bands. High performance of photodiodes fabricated on MBE HgCdTe layers reflects on the overall quality of the grown material. The photodiodes were planar p-on-n junctions fabricated by As ion-implantation into indium doped, n-type, in situ grown double layer heterostructures. At 77K, diodes fabricated on MBE Hg_1−xCd_xTe with x ≈ 0.30 (λ_co ≈ 5.6 μm), x ≈ 0.26 (λ_co ≈ 7 μm), x ≈ 0.23 (λ_co ≈ 10 μm) show R₀A products in excess of 1 x 10⁶ ohm-cm², 7 x 10⁵ ohm-cm², and 3 x 10² ohm-cm², respectively. These devices also show high quantum efficiency. As a means to assess the uniformity of the MBE HgCdTe material, two-dimensional 64 x 64 and 128 x 128 mosaic detector arrays were hybridized to Si multiplexers. These focal plane arrays show an operability as high as 97% at 77K for the x ≈ 0.23 spectral band and 93% at 77K for the x ≈ 0.26 spectral band. The operability is limited partly by the density of void-type defects that are present in the MBE grown layers and are easily identified under an optical microscope.     

MR angiography of the spine

Postcontrast MR angiography complements the standard spinal MR imaging study by improving detection and display of normal and abnormal intradural vessels, primarily veins. Detection of abnormal veins facilitates diagnosis of spinal vascular malformations and vascular tumors. The most useful application has been in screening for spinal dural arteriovenous fistula, in which MR angiography demonstrates the medullary vein into which the fistula drains, thus allowing noninvasive identification of the spinal level of the fistula.     

Pin force measurement in a halo-vest orthosis, in vivo

Salmon calcitonin (sCT) is an example of one of the many bioactive peptides that require amidation of the carboxy terminus for full potency. We describe a method for the production of amidated sCT in the mammary gland of transgenic rabbits. Expression of a fusion protein comprising human alpha lactalbumin joined by an enterokinase cleavable linker to sCT was directed to the mammary gland under the control of the ovine beta lactoglobulin promoter. C-terminal amidation in vivo was achieved by extending the sCT by a single glycine residue that provides a substrate for endogenous amidating activity in the mammary gland. Full characterization of the released sCT demonstrated it to be equivalent to synthetic standard in terms of structure, purity, and potency.