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A computational protocol for particle tracking in wellfields with lakes is proposed. The protocol is demonstrated in the Northwest Wellfield, which is the largest wellfield in Florida and contains many lakes. Comparison of the results with existing regulatory travel-time contours shows that the proposed method produces more realistic results in terms of reflecting the presence of lakes. DOI: 10.1061/(ASCE)WR.1943-5452.0000032 CE Database subject headings: Particles; Travel time; Groundwater; Lakes. Author keywords: Particle tracking; Travel time; Wellhead protection; Groundwater; Lakes.

Perceived wisdom within the construction industry is that different Forensic Schedule Analysis (FSA) methods produce different results on the same set of facts. Although there are many potential variables that could cause this, such as bias of the analyst or the quality of the implementation of a method, some experts have expressed concern that because the methods themselves generate different results, some may be potentially defective. This paper will explore that question by examining a specific set of facts and applying each of the four major FSA methods - as-planned versus as-built (APAB), Windows, time impact analysis (TIA) and Collapsed As- Built (CAB) - to those facts. Further, the paper will explain how and why that occurs, how to quantify and reconcile the differences and what conclusions a FSA expert should draw from those differences. [ABSTRACT FROM AUTHOR]

Nuclear receptors such as the estrogen receptors (ERα and ERβ) modulate the effects of the estrogen hormones and are important targets for design of innovative chemotherapeutic agents for diseases such as breast cancer and osteoporosis. Conjugate and bifunctional compounds which incorporate an ER ligand offer a useful method of delivering cytotoxic drugs to tissue sites such as breast cancers which express ERs. A series of novel conjugate molecules incorporating both the ER ligands endoxifen and cyclofenil-endoxifen hybrids covalently linked to the antimitotic and tubulin targeting agent combretastatin A-4 were synthesised and evaluated as ER ligands. A number of these compounds demonstrated pro-apoptotic effects, with potent antiproliferative activity in ER-positive MCF-7 breast cancer cell lines and low cytotoxicity. These conjugates displayed binding affinity towards ERα and ERβ isoforms at nanomolar concentrations e.g., the cyclofenil-amide compound 13e is a promising lead compound of a clinically relevant ER conjugate with IC50 in MCF-7 cells of 187 nM, and binding affinity to ERα (IC50 = 19 nM) and ERβ (IC50 = 229 nM) while the endoxifen conjugate 16b demonstrates antiproliferative activity in MCF-7 cells (IC50 = 5.7 nM) and binding affinity to ERα (IC50 = 15 nM) and ERβ (IC50 = 115 nM). The ER binding effects are rationalised in a molecular modelling study in which the disruption of the ER helix-12 in the presence of compounds 11e, 13e and 16b is presented These conjugate compounds have potential application for further development as antineoplastic agents in the treatment of ER positive breast cancers [ABSTRACT FROM AUTHOR]