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Activation of the tyrosine kinase c-Src promotes breast cancer progression and poor outcomes, yet the underlying mechanisms are incompletely understood. Here, we have shown that deletion of c-Src in a genetically engineered model mimicking the luminal B molecular subtype of breast cancer abrogated the activity of forkhead box M1 (FOXM1), a master transcriptional regulator of the cell cycle. We determined that c-Src phosphorylated FOXM1 on 2 tyrosine residues to stimulate its nuclear localization and target gene expression. These included key regulators of [G.sub.2]/M cell-cycle progression as well as c-Src itself, forming a positive feedback loop that drove proliferation in genetically engineered and patient-derived models of luminal B-like breast cancer. Using genetic approaches and small molecules that destabilize the FOXM1 protein, we found that targeting this mechanism induced [G.sub.2]/M cell-cycle arrest and apoptosis, blocked tumor progression, and impaired metastasis. We identified a positive correlation between FOXM1 and c-Src expression in human breast cancer and show that the expression of FOXM1 target genes predicts poor outcomes and associates with the luminal B subtype, which responds poorly to currently approved therapies. These findings revealed a regulatory network centered on c-Src and FOXM1 that is a targetable vulnerability in aggressive luminal breast cancers., Introduction Breast cancer comprises a range of histopathological and molecular subtypes differing in metastatic capacity, response to therapies, and clinical outcomes (1). Transcriptomic profiling has identified at least 5 breast [...]

Byline: Najah. Alanizy, Ehab. Attalla, Ahmed. Abdelaal, Mohamed. Yassen, Medhat. Shafaa Grid radiotherapy is one of the treatment techniques applied to treat patients with advanced bulky tumors. Purpose: This study [...]

Byline: Mohamed. Ibrahim, Ehab. Attalla, Mostafa. El Naggar, Wael. Elshemey Background: To evaluate the pros and cons of 9-field intensity modulated radiotherapy (IMRT) compared to 7-field IMRT in the treatment [...]

Byline: Reham. Sherif, Wael. Elshemey, Ehab. Attalla BACKGROUND: Craniospinal irradiation (CSI) is the standard radiation therapy treatment for medulloblastoma. The aim of this study was to estimate and compare the [...]

Byline: Ola. Bakry, Mohamed. Shoeib, Noha. El Kady, Shereen. Attalla Background: Vitiligo is a common pigmentary disorder. Studies on its pathogenesis extensively investigated melanocytes' abnormalities and few studies searched for [...]

This study analyzes the consumption quantities and costs of energy, water, and gas for a sample of 10 conventional and 20 energy-retrofitted public schools in Toronto over a 5 year study period to establish a benchmark for the consumption of energy in traditional versus more sustainable buildings. Through extensive statistical analysis of the data collected, the study demonstrates that electricity and gas consumption quantities and costs decrease more significantly in energy-retrofitted schools than in conventional schools. Whereas energy-retrofitted schools consume and spend on average as much money on energy as conventional schools, energy-retrofitted schools consume and spend more money on electricity and less money on gas than conventional schools. Energy-retrofitted schools also exhibit stronger and more significant positive relationships between the quantities of electricity, water, and gas consumed per user in those schools and the schools' total number of users than conventional schools. Key words: conventional schools, energy-retrofitted schools, energy, water, gas consumption quantities and costs. La presente etude analyse les quantitees et les couts d'energie, d'eau et de gaz consommes pour un echantillon de 10 ecoles publiques conventionnelles et de 20 ecoles publiques ayant subi des renovations energetiques dans Toronto au cours d'une periode de cinq ans, afin d'etablir une reference pour la consommation d'energie dans les batiments conventionnels par rapport a des batiments plus ecologiques. Grace a une analyse statistique detailleee des donnees colligeees, l'etude demontre que les quantitees et les couts d'electricitee et de gaz consommes diminuent de maniere plus importante dans les ecoles ayant subi des renovations energetiques que dans les ecoles conventionnelles. Alors que les ecoles renovees consomment et depensent en moyenne autant d'argent en energie que les ecoles conventionnelles, les ecoles reenoveees consomment et depensent plus d'argent en electricite et moins en gaz que les ecoles conventionnelles. Les ecoles renovees montrent egalement une meilleure relation beaucoup plus positive entre les quantitees d'electricite, d'eau et de gaz consommeees par utilisateur dans ces ecoles et pour le nombre total d'utilisateurs des ecoles que dans les ecoles conventionnelles. Mots-cles: ecoles conventionnelles, ecoles ayant subi des renovations energetiques, quantites et couts de l'energie, de l'eau et du gaz consommes. [Traduit par la Redaction], 1. Introduction In the past, architectural, engineering, and construction projects were primarily concerned with the creation and building of new infrastructure. With the massive investment in building new infrastructure, the [...]

The aging infrastructure in North America and worldwide mandates large investments in repair and improvement (R&I) activities. For organizations that own many assets, managing a large number of R&I activities is not a simple task and requires accurate estimating and scheduling so that proper budgeting and resource allocation decisions can be made. To support these decisions, this paper introduces a Web-based system that estimates the cost and duration of a user-requested R&I activity and provides alternative schedules based on resource availability. For estimating, the Web-based system hosts 32 artificial neural networks (ANNs), trained on actual historical data, for 32 common R&I activities in building projects. Each ANN incorporates a sensitivity analysis to consider the uncertainty in the input parameters on the estimate, and is linked to a central scheduling algorithm for resource allocation based on a first-come first-serve basis. The automated system helps practitioners in planning numerous R&I requests with least time, cost, and paper work. Details on system development are provided in this paper along with perceived benefits and the opinion of users on its performance. DOI: 10.1061/(ASCE)0733-9364(2008)134:5(342) CE Database subject headings: Estimation; Scheduling; Computer applications; Reconstruction; Maintenance costs; Infrastructure.

A new technique is proposed for generating initial orthonormal eigenvectors of the discrete Fourier transform matrix F by the singular-value decomposition of its orthogonal projection matrices on its eigenspaces and efficiently computable expressions for those matrices are derived. In order to generate Hermite-Gaussian-like orthonormal eigenvectors of F given the initial ones, a new method called the sequential orthogonal procrustes algorithm (SOPA) is presented based on the sequential generation of the columns of a unitary matrix rather than the batch evaluation of that matrix as in the OPA. It is proved that for any of the SOPA, the OPA, or the Gram--Schmidt algorithm (GSA) the output Hermite-Gaussian-like orthonormal eigenvectors are invariant under the change of the input initial orthonormal eigenvectors. Index Terms--Discrete fractional Fourier transform (DFRFT), Gram-Schmidt algorithm (GSA), Hermite-Gaussian-like eigenvectors, orthogonal procrustes algorithm (OPA), sequential OPA (SOPA), singular-value decomposition.

As compared with new construction, reconstruction of operational facilities exhibits a higher challenge, particularly when multiple projects are involved. For owner organizations involved in such projects, use of in-house resources versus outside contractors has been a major dilemma, with each approach having its potential benefits. This paper uses a real-life case study approach to investigate the delivery of 800 small reconstruction projects using in-house forces. Details are described related to the prioritization, budgeting, organization structure, and the mechanisms used for staff allocation. It was found that the main characteristics of projects that are best delivered by in-house forces include high urgency and inadequate scope definition. Outsourcing this type of projects exposes the owner to a large number of changes and their consequent cost overruns/delays. Based on the case study, the challenges facing in-house delivered projects and the factors that contribute to their success were investigated and outlined. To verify the findings a questionnaire survey among similar organizations is conducted and its results discussed. DOI: 10.1061/(ASCE)0742-597X(2004)20:1(25) CE Database subject headings: Reconstruction; Scheduling; Delivery; Project management.

This paper investigates the challenging environment of reconstruction projects and describes the development of a predictive model of cost deviation in such high-risk projects. Based on a survey of construction professionals, information was obtained on the reasons behind cost overruns and poor quality from 50 reconstruction projects. For each project, the specific techniques used for project control were reported along with the actual cost deviation from planned values. Two indicators of cost deviation are used in this study: cost overrun to the owner, and the cost of rework to the contractor. Based on the information obtained, 36 factors were identified as having direct impact on the cost performance of reconstruction projects. Two techniques were then used to develop models for predicting cost deviation: statistical analysis, and artificial neural networks (ANNs). While both models had similar accuracy, the ANN model is more sensitive to a larger number of variables. Overall, this study contributes to a better understanding of the reasons for cost deviation in reconstruction projects and provides a decision support tool to quantify that deviation. DOI: 10.1061/(ASCE)0733-9364(2003)129:4(405) CE Database subject headings: Construction management; Reconstruction; Cost control; Retrofitting; Project management.

Cost, schedule, and quality are the main indicators of performance in construction projects. These indicators are highly interrelated and require some balance and trade-off among them to achieve efficient overall control over project performance. Focusing on these performance indicators, the primary objective of this study is to investigate the use of conventional control techniques in projects involving reconstruction of occupied buildings. To facilitate this analysis, performance data have been collected, using a questionnaire survey, from 25 reconstruction and 15 new construction projects. The survey was followed by structured interviews with construction practitioners and project participants to elicit success-related factors and to identify some of the unique problems affecting the control of reconstruction projects. Using the collected data, performance comparison was conducted between new and reconstruction projects along with a detailed analysis of the suitability of existing techniques for the control of the cost, schedule, and quality in reconstruction projects.

The paper describes a method of inelastic analysis for steel frames that provides the accuracy of distributed plasticity methods with the computational efficiency of elastic-plastic-hinge methods. It accounts for spread-of-plasticity effects without the need for through-section and lengthwise discretization of a beam-column element. This is accomplished through nonlinear equations for the force-strain relationships of the cross section that are calibrated to data from inelastic analyses and numerical integration of the cross-section model along the element length to obtain inelastic flexibility coefficients for the member. The flexibility coefficients are employed in generating an inelastic stiffness matrix in which geometric nonlinearity is also accounted for. The proposed model has been implemented and tested using several example problems known to be sensitive to spreading-plasticity effects.

Byline: Hassan. Abou-elenein, Ehab. Attalla, H. Ammar, Ismail. Eldesoky, Mohamed. Farouk, Mohamed. Zaghloul The improvement in conformal radiotherapy techniques enables us to achieve steep dose gradients around the target which [...]

Byline: Ehab. Attalla, H. Abo-Elenein, H. Ammar, Ismail. El-Desoky Dosimetric properties of virtual wedge (VW) and physical wedge (PW) in 6- and 10-MV photon beams from a Siemens ONCOR linear [...]