The cell surface glycoprotein CUB domain-containing protein 1 (CDCP1) contributes to epidermal growth factor receptor-mediated cell migration

Epidermal growth factor (EGF) activation of the EGF receptor (EGFR) is an important mediator of cell migration, and aberrant signaling via this system promotes a number of malignancies including ovarian cancer. We have identified the cell surface glycoprotein CDCP1 as a key regulator of EGF/EGFR-induced cell migration. We show that signaling via EGF/EGFR induces migration of ovarian cancer Caov3 and OVCA420 cells with concomitant up-regulation of CDCP1 mRNA and protein. Consistent with a role in cell migration CDCP1 relocates from cell-cell junctions to punctate structures on filopodia after activation of EGFR. Significantly, disruption of CDCP1 either by silencing or the use of a function blocking antibody efficiently reduces EGF/EGFR-induced cell migration of Caov3 and OVCA420 cells. We also show that up-regulation of CDCP1 is inhibited by pharmacological agents blocking ERK but not Src signaling, indicating that the RAS/RAF/MEK/ERK pathway is required downstream of EGF/EGFR to induce increased expression of CDCP1. Our immunohistochemical analysis of benign, primary, and metastatic serous epithelial ovarian tumors demonstrates that CDCP1 is expressed during progression of this cancer. These data highlight a novel role for CDCP1 in EGF/EGFR-induced cell migration and indicate that targeting of CDCP1 may be a rational approach to inhibit progression of cancers driven by EGFR signaling including those resistant to anti-EGFR drugs because of activating mutations in the RAS/RAF/MEK/ERK pathway.

The Spartan-3E Tutorial 2 : Introduction to using the PicoBlaze Microcontroller Version 1.0

This tutorial is designed to help new users become familiar with using the PicoBlaze microcontroller with the Spartan-3E board. The tutorial gives a brief introduction to the PicoBlaze microcontroller, and then steps through the following: - Writing a small PicoBlaze assembly language (.psm) file, and stepping through the process of assembling the .psm file using KCPSM3; - Writing a top level VHDL module to connect the PicoBlaze microcontroller (KCPSM3 component) and the program ROM, and to connect the required input and output ports; - Connecting the top level module inputs and outputs to the switches, buttons and LEDs on the Spartan-3E board; - Downloading the program to the Spartan-3E board using the Project Navigator software.

Antenatal ureaplasma infection impairs development of the fetal ovine gut in an IL-1-dependent manner

Ureaplasma infection of the amniotic cavity is associated with adverse postnatal intestinal outcomes. We tested whether interleukin-1 (IL-1) signaling underlies intestinal pathology following ureaplasma exposure in fetal sheep. Pregnant ewes received intra-amniotic injections of ureaplasma or culture media for controls at 3, 7, and 14 d before preterm delivery at 124 d gestation (term 150 d). Intra-amniotic injections of recombinant human interleukin IL-1 receptor antagonist (rhIL-1ra) or saline for controls  were given 3 h before and every 2 d after Ureaplasma injection. Ureaplasma exposure caused fetal gut inflammation within 7 d with damaged villus epithelium and gut barrier loss. Proliferation, differentiation, and maturation of enterocytes were significantly reduced after 7 d of ureaplasma exposure, leading to severe villus atrophy at 14 d. Inflammation, impaired development and villus atrophy of the fetal gut was largely prevented by intra-uterine rhIL-1ra treatment. These data form the basis for a clinical understanding of the role of ureaplasma in postnatal intestinal pathologies.

Krüppel-associated box (KRAB)-associated co-repressor (KAP-1) Ser-473 phosphorylation regulates heterochromatin protein 1 (HP1- ) mobilization and DNA repair in heterochromatin

The DNA damage response encompasses a complex series of signaling pathways that function to regulate and facilitate the repair of damaged DNA. Recent studies have shown that the repair of transcriptionally inactive chromatin, named heterochromatin, is dependent upon the phosphorylation of the co-repressor, Krüppel-associated box (KRAB) domain-associated protein (KAP-1), by the ataxia telangiectasia-mutated (ATM) kinase. Co-repressors, such as KAP-1, function to regulate the rigid structure of heterochromatin by recruiting histone-modifying enzymes, such HDAC1/2, SETDB1, and nucleosome-remodeling complexes such as CHD3. Here, we have characterized a phosphorylation site in the HP1-binding domain of KAP-1, Ser-473, which is phosphorylated by the cell cycle checkpoint kinase Chk2. Expression of a nonphosphorylatable S473A mutant conferred cellular sensitivity to DNA-damaging agents and led to defective repair of DNA double-strand breaks in heterochromatin. In addition, cells expressing S473A also displayed defective mobilization of the HP1-β chromodomain protein. The DNA repair defect observed in cells expressing S473A was alleviated by depletion of HP1-β, suggesting that phosphorylation of KAP-1 on Ser-473 promotes the mobilization of HP1-β from heterochromatin and subsequent DNA repair. These results suggest a novel mechanism of KAP-1-mediated chromatin restructuring via Chk2-regulated HP1-β exchange from heterochromatin, promoting DNA repair.

Motorcycle Safety Research Project Interim Summary Report Research Deliverable 1: Investigate and Develop a Pre-learner Motorcycle Licensing Package

Motorcycle trauma is a serious road safety issue in Queensland and throughout Australia. In 2009, Queensland Transport (later Transport and Main Roads or TMR) appointed CARRS-Q to provide a three-year program of Road Safety Research Services for Motorcycle Rider Safety. Funding for this research originated from the Motor Accident Insurance Commission. This program of research was undertaken to produce knowledge to assist TMR to improve motorcycle safety by further strengthening the licensing and training system to make learner riders safer by developing a pre-learner package (Deliverable 1 which is the focus of this report), and by evaluating the Q-Ride CAP program to ensure that it is maximally effective and contributes to the best possible training for new riders (Deliverable 2), which is the focus of this report. Deliverable 3 of the program identified potential new licensing components that will reduce the incidence of risky riding and improve higher-order cognitive skills in new riders. While fatality and injury rates for learner car drivers are typically lower than for those with intermediate licences, this pattern is not found for learner motorcycle riders. Learner riders cannot be supervised as effectively as learner car drivers and errors are more likely to result in injury for learner riders than learner drivers. It is therefore imperative to improve safety for learner riders. Deliverable 1 examines the potential for improving the motorcycle learner and licence scheme by introducing a pre-learner motorcycle licensing and training scheme within Queensland. The tasks undertaken for Deliverable 1 were a literature review, analysis of learner motorcyclist crash and licensing data, and the development of a potential pre-learner motorcycle rider program.

Non-rhetorical journalism? A case study of Absudo [Jornalismo (não) retórico? Um estudo de caso sobre o Abusado]

Resumo: A proposta do artigo é discutir a possibilidade de um jornalismo não-retórico, pelo viés do acontecer poético, no romance-reportagem Abusado: o dono do morro Dona Marta, do jornalista Caco Barcellos. Retoma, nesse empreendimento, a reflexão do filósofo Michel Foucault sobre a construção discursiva da figura do delinquente. Com isso, a construção biográfica do traficante Márcio Amaro de Oliveira aparece como imagem-questão, anunciadora de novas perguntas e inquietações sobre a realidade da favela da Santa Marta, ao invés de uma simples construção discursiva sobre o real.

4-Amino-N-(4,6-dimethylpyrimidin-2-yl)benzenesulfonamide--2-nitrobenzoic acid (1/1)

In the asymmetric unit of the title co-crystal, C12H14N4O2S·C7H5NO4, the sulfamethazine and 2-nitrobenzoic acid molecules form a heterodimer through intermolecular amide-carboxylic acid N-HO and carboxylic acid-pyrimidine O-HN hydrogen-bond pairs, giving a cyclic motif [graph set R22(8)]. The dihedral angle between the two aromatic ring systems in the sulfamethazine molecule is 88.96 (18)° and the nitro group of the acid is 50% rotationally disordered. Secondary aniline N-HOsulfone hydrogen-bonding associations give a two-dimensional structure lying parallel to the ab plane.

The effect of Yb addition in bi2sr2ca 1-xybxcu2oy partial melted thick films

To study the phase relations in the Bi-2212 and Yb2O3 system, Bi2Sr2Ca1-xYbxCu 2Oy thick films are prepared by partial melt processing via an intermediate reaction between Bi-2212 and Yb2O3. When Bi-2212 and Yb2O3 are partially melted and then slowly cooled, solid solutions of Bi2Sr2Ca 1-xYbxCu2Oy, form by reactions between liquid and solid phases which contain Yb. Following these reactions, Ca is partially replaced in Bi-2212 matrix and participates in the formation of secondary phases, such as Bi-free, (Ca, Sr)Ox and CaO. Variation of the Bi-2212-Yb2O3 ratios and processing parameters changes the balance between the phases and leads to different Yb:Ca ratios in the Bi-2212 matrix of processed thick films. When the partial melting process is optimized for each sample to minimize the growth of secondary phases, x = 0.42-0.46 for the samples prepared at pO2 = 0.01 atm, x = 0.24-0.29 for the samples prepared at pO2 = 0.21 atm, x = 0.18-0.23 for the samples prepared at pO2 = 0.99 atm are obtained regardless to the starting compositions. It is found that superconducting properties of Bi 2Sr2Ca1-xYbxCu2O y thick films strongly depend on the processing conditions, because the conditions result in different Yb content in the Bi-2212 matrix and the volume fraction of the secondary phases. The highest Tc(0) of 77, 90 and 91 K were obtained for the samples processed at 0.01, 0.21 and 0.99 atm of O2, respectively.

The product of text and 'Other' statements : discourse analysis and the critical use of Foucault

Much has been written on Michel Foucault’s reluctance to clearly delineate a research method, particularly with respect to genealogy (Harwood 2000; Meadmore, Hatcher, & McWilliam 2000; Tamboukou 1999). Foucault (1994, p. 288) himself disliked prescription stating, “I take care not to dictate how things should be” and wrote provocatively to disrupt equilibrium and certainty, so that “all those who speak for others or to others” no longer know what to do. It is doubtful, however, that Foucault ever intended for researchers to be stricken by that malaise to the point of being unwilling to make an intellectual commitment to methodological possibilities. Taking criticism of “Foucauldian” discourse analysis as a convenient point of departure to discuss the objectives of poststructural analyses of language, this paper develops what might be called a discursive analytic; a methodological plan to approach the analysis of discourses through the location of statements that function with constitutive effects.

Slid pairs in the initialisation of the A5/1 stream cipher

A5/1 is a shift register based stream cipher which uses a majority clocking rule to update its registers. It is designed to provide privacy for the GSM system. In this paper, we analyse the initialisation process of A5/1. We demonstrate a sliding property of the A5/1 cipher, where every valid internal state is also a legitimate loaded state and multiple key-IV pairs produce phase shifted keystream sequences. We describe a possible ciphertext only attack based on this property.

Anatomical MR imaging of long bones : comparative performance of MRI at 1.5 T and 3 T

The current gold standard for the design of orthopaedic implants is 3D models of long bones obtained using computed tomography (CT). However, high-resolution CT imaging involves high radiation exposure, which limits its use in healthy human volunteers. Magnetic resonance imaging (MRI) is an attractive alternative for the scanning of healthy human volunteers for research purposes. Current limitations of MRI include difficulties of tissue segmentation within joints and long scanning times. In this work, we explore the possibility of overcoming these limitations through the use of MRI scanners operating at a higher field strength. We quantitatively compare the quality of anatomical MR images of long bones obtained at 1.5 T and 3 T and optimise the scanning protocol of 3 T MRI. FLASH images of the right leg of five human volunteers acquired at 1.5 T and 3 T were compared in terms of signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR). The comparison showed a relatively high CNR and SNR at 3 T for most regions of the femur and tibia, with the exception of the distal diaphyseal region of the femur and the mid diaphyseal region of the tibia. This was accompanied by an ~65% increase in the longitudinal spin relaxation time (T1) of the muscle at 3 T compared to 1.5 T. The results suggest that MRI at 3 T may be able to enhance the segmentability and potentially improve the accuracy of 3D anatomical models of long bones, compared to 1.5 T. We discuss how the total imaging times at 3 T can be kept short while maximising the CNR and SNR of the images obtained.

Years lived with disability (YLDs) for 1160 sequelae of 289 diseases and injuries 1990–2010 : a systematic analysis for the Global Burden of Disease Study 2010

Background Non-fatal health outcomes from diseases and injuries are a crucial consideration in the promotion and monitoring of individual and population health. The Global Burden of Disease (GBD) studies done in 1990 and 2000 have been the only studies to quantify non-fatal health outcomes across an exhaustive set of disorders at the global and regional level. Neither effort quantified uncertainty in prevalence or years lived with disability (YLDs). Methods Of the 291 diseases and injuries in the GBD cause list, 289 cause disability. For 1160 sequelae of the 289 diseases and injuries, we undertook a systematic analysis of prevalence, incidence, remission, duration, and excess mortality. Sources included published studies, case notification, population-based cancer registries, other disease registries, antenatal clinic serosurveillance, hospital discharge data, ambulatory care data, household surveys, other surveys, and cohort studies. For most sequelae, we used a Bayesian meta-regression method, DisMod-MR, designed to address key limitations in descriptive epidemiological data, including missing data, inconsistency, and large methodological variation between data sources. For some disorders, we used natural history models, geospatial models, back-calculation models (models calculating incidence from population mortality rates and case fatality), or registration completeness models (models adjusting for incomplete registration with health-system access and other covariates). Disability weights for 220 unique health states were used to capture the severity of health loss. YLDs by cause at age, sex, country, and year levels were adjusted for comorbidity with simulation methods. We included uncertainty estimates at all stages of the analysis. Findings Global prevalence for all ages combined in 2010 across the 1160 sequelae ranged from fewer than one case per 1 million people to 350 000 cases per 1 million people. Prevalence and severity of health loss were weakly correlated (correlation coefficient −0·37). In 2010, there were 777 million YLDs from all causes, up from 583 million in 1990. The main contributors to global YLDs were mental and behavioural disorders, musculoskeletal disorders, and diabetes or endocrine diseases. The leading specific causes of YLDs were much the same in 2010 as they were in 1990: low back pain, major depressive disorder, iron-deficiency anaemia, neck pain, chronic obstructive pulmonary disease, anxiety disorders, migraine, diabetes, and falls. Age-specific prevalence of YLDs increased with age in all regions and has decreased slightly from 1990 to 2010. Regional patterns of the leading causes of YLDs were more similar compared with years of life lost due to premature mortality. Neglected tropical diseases, HIV/AIDS, tuberculosis, malaria, and anaemia were important causes of YLDs in sub-Saharan Africa. Interpretation Rates of YLDs per 100 000 people have remained largely constant over time but rise steadily with age. Population growth and ageing have increased YLD numbers and crude rates over the past two decades. Prevalences of the most common causes of YLDs, such as mental and behavioural disorders and musculoskeletal disorders, have not decreased. Health systems will need to address the needs of the rising numbers of individuals with a range of disorders that largely cause disability but not mortality. Quantification of the burden of non-fatal health outcomes will be crucial to understand how well health systems are responding to these challenges. Effective and affordable strategies to deal with this rising burden are an urgent priority for health systems in most parts of the world. Funding Bill & Melinda Gates Foundation.

The Spartan-3E tutorial 3 : using the LCD display [version 1.0]

This tutorial is designed to assist users who wish to use the LCD screen on the Spartan-3E board. In this tutorial, the PicoBlaze microcontroller is used to control the LCD. The tutorial is organised into three Parts. In Part A, code is written to display the message "Hello World" on the LCD. Part B demonstrates how to define and display custom characters. Finally, Part C shows how the display can be shifted and flashed. Shifting is done by using a delay in the main PicoBlaze program loop, while flashing is done using the PicoBlaze interrupt. The slider switches can be used to select the shifting direction, and to turn shifting and flashing on and off.

Debts “incurred” by receivers, administrators and liquidators : the case for a harmonised construction of ss 419, 443A and 556(1)(a) of the Corporations Act

This article analyses the inconsistent approaches taken by courts when interpreting provisions of the Corporations Act which address debts or expenses “incurred” by receivers, administrators and liquidators. The article contends for a consistent construction of these provisions which will enable the legislation to operate (as was intended) for the benefit of persons who supply goods, services or labour to companies in external administration. The article explains how and why debts can be “incurred” by insolvency practitioners continuing on pre-existing contracts. Specifically, the article contends for a construction of ss 419 and 443A of the Corporations Act which renders receivers and administrators personally liable for certain entitlements of employees (eg, wages and superannuation contributions) which become due and payable by reason of the decision of a receiver or administrator to continue a pre-existing contract rather than terminate it.