Disruption of Vitamin D and Calcium Signaling in Keratinocytes Predisposes to Skin Cancer.

1,25 dihydroxyvitamin D (1,25(OH)2D), the active metabolite of vitamin D, and calcium regulate epidermal differentiation. 1,25(OH)2D exerts its effects through the vitamin D receptor (VDR), a transcription factor in the nuclear hormone receptor family, whereas calcium acts through the calcium sensing receptor (Casr), a membrane bound member of the G protein coupled receptor family. We have developed mouse models in which the Vdr and Casr have been deleted in the epidermis ((epid) Vdr (-∕-) and (epid) Casr (-∕-)). Both genotypes show abnormalities in calcium induced epidermal differentiation in vivo and in vitro, associated with altered hedgehog (HH) and β-catenin signaling that when abnormally expressed lead to basal cell carcinomas (BCC) and trichofolliculomas, respectively. The Vdr (-∕-) mice are susceptible to tumor formation following UVB or chemical carcinogen exposure. More recently we found that the keratinocytes from these mice over express long non-coding RNA (lncRNA) oncogenes such as H19 and under express lncRNA tumor suppressors such as lincRNA-21. Spontaneous tumors have not been observed in either the (epid) Vdr (-∕-) or (epid) Casr (-∕-). But in mice with epidermal specific deletion of both Vdr and Casr ((epid) Vdr (-∕-)/(epid) Casr (-∕-) [DKO]) tumor formation occurs spontaneously when the DKO mice are placed on a low calcium diet. These results demonstrate important interactions between vitamin D and calcium signaling through their respective receptors that lead to cancer when these signals are disrupted. The roles of the β-catenin, hedgehog, and lncRNA pathways in predisposing the epidermis to tumor formation when vitamin D and calcium signaling are disrupted will be discussed

Workflow Critical Path: A Data-oriented Critical path metric for Holistic HPC Workflows

Current trends in HPC, such as the push to exascale, convergence with Big Data, and growing complexity of HPC applications, have created gaps that traditional performance tools do not cover. One example is Holistic HPC Workflows — HPC workflows comprising multiple codes, paradigms, or platforms that are not developed using a workflow management system. To diagnose the performance of these applications, we define a new metric called Workflow Critical Path (WCP), a data-oriented metric for Holistic HPC Workflows. WCP constructs graphs that span across the workflow codes and platforms, using data states as vertices and data mutations as edges. Using cloud-based technologies, we implement a prototype called Crux, a distributed analysis tool for calculating and visualizing WCP. Our experiments with a workflow simulator on Amazon Web Services show Crux is scalable and capable of correctly calculating WCP for common Holistic HPC workflow patterns. We explore the use of WCP and discuss how Crux could be used in a production HPC environment

Automated Mobile System for Accurate Outdoor Tree Crop Enumeration Using an Uncalibrated Camera.

This paper demonstrates an automated computer vision system for outdoor tree crop enumeration in a seedling nursery. The complete system incorporates both hardware components (including an embedded microcontroller, an odometry encoder, and an uncalibrated digital color camera) and software algorithms (including microcontroller algorithms and the proposed algorithm for tree crop enumeration) required to obtain robust performance in a natural outdoor environment. The enumeration system uses a three-step image analysis process based upon: (1) an orthographic plant projection method integrating a perspective transform with automatic parameter estimation; (2) a plant counting method based on projection histograms; and (3) a double-counting avoidance method based on a homography transform. Experimental results demonstrate the ability to count large numbers of plants automatically with no human effort. Results show that, for tree seedlings having a height up to 40 cm and a within-row tree spacing of approximately 10 cm, the algorithms successfully estimated the number of plants with an average accuracy of 95.2% for trees within a single image and 98% for counting of the whole plant population in a large sequence of images

Optical thickness measurement with multi-wavelength THz interferometry

AbstractWe report unambiguous thickness measurement with an all-optical THz source. The optical thickness variation of a test target was measured in a Mach–Zehnder interferometer to approximately 0.5% of the illumination wavelength using an optical parametric THz laser. The frequency of the laser was continuously tuneable, enabling a synthetic wavelength to be produced by sequential illumination at discrete frequencies, thus extending the unambiguous measurement range to half the synthetic wavelength. The all-optical source provides some advantages with respect to opto-electronic and electronic sources, particularly measurement speed and resolution

Histidine-rich protein II nanoparticle delivery of heme iron load drives endothelial inflammation in cerebral malaria

Histidine-rich protein II (HRPII) is secreted b

Transfer Pricing by Multinational Firms: New Evidence from Foreign Firm Ownerships

Using a firm-level panel dataset covering the universe of Danish exports between 1999 and 2006, we find robust evidence for profit shifting by multinational corporations (MNC) through transfer pricing. Our triple difference estimation method corrects for a downward bias in previous studies. The bias results from MNCs adjusting their arm's length prices to obscure the extent of their transfer price manipulations. Our identification strategy exploits the movement in export prices to a destination in response to: (1) the establishment of a foreign affiliate by an exporter to that destination, and (2) a change in the foreign corporate tax rates. Once owning an affiliate in a country with a corporate tax rate lower than in the home country, Danish multinationals reduce the unit values of their exports there between 5.7 to 9.1 percent, on average. This reduction corresponds to $141 million in underreported export revenues in year 2006, which translates into a loss in tax income equal to 3.24 percent of Danish MNCs' tax returns

Low dose CT vs plain abdominal radiography for the investigation of the acute abdomen

Background: To compare low-dose abdominal computed tomography (LDCT) with plain abdominal radiography (AR) in the primary investigation of acute abdominal pain to determine if there is a difference in diagnostic yield, the number of additional investigations required and hospital length of stay (LOS). Methods: This randomized controlled trial was approved by the institutional review board, and informed consent was obtained. Patients presenting to the emergency department with an acute abdomen and who would normally be investigated with AR were randomized to either AR or LDCT. The estimated radiation dose of the LDCT protocol was 2–3 mSv compared to 1.1 mSv for AR. Pearson\u27s chi-square and the independent samples t-test were used for the statistical analysis. Results: A total of 142 patients were eligible, and after exclusions and omitting those with incomplete data, 55 patients remained for analysis in the AR arm and 53 in the LDCT arm. A diagnosis could be obtained in 12 (21.8%) patients investigated with AR compared to 34 (64.2%) for LDCT (P \u3c 0.001). Twenty-eight (50.9%) patients in the AR group required further imaging during their admission compared to 14 (26.4%) in the LDCT group (P= 0.009). There was no difference in the median hospital LOS (3.84 days for AR versus 4.24 days for LDCT, P= 0.83). Conclusion: LDCT demonstrates a superior diagnostic yield over AR and reduces the number of subsequent imaging tests for a minimal cost in radiation exposure. However, there is no difference in the overall hospital LOS between the two imaging strategies