DIFFUSE POLLUTION ‐ WHAT IS THE NATURE OF THE PROBLEM?

This paper considers recent developments in the understanding of diffuse pollution, its generation, transport and impacts. The relative importance of diffuse sources to total pollutant loading must be identified in order to develop appropriate strategies for management.
Research has indicated that individual diffuse pollutants respond differently to changing flow conditions and that there is a widespread misconception that higher flows are associated with lower pollutant concentrations. Evidence is presented to highlight this discrepancy and a rationale for load assessment is presented. The implications of this for monitoring within the context of the EU Water Framework Directive are discussed as are the implications for the mitigation of diffuse pollution.     

In the echoes of gunfire: Practicing psychologists' responses to school violence.

The recent rash of school shootings has thrust practicing psychologists into the role of assisting communities prevent such high profile incidents of juvenile violence. Although many psychologists are involved in assessing and treating children at risk for violent behavior, their efforts are rarely linked with other organized prevention efforts. This article describes how practicing psychologists represent a critical resource to school districts in developing and implementing a comprehensive violence prevention strategy. The authors outline a model school and mental health clinic collaborative program that can be replicated in various practice settings and discuss the benefits and essential steps for building such a collaboration. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Affinity,Specificity, and Cooperativity of DNA Binding by Bacterial Gene Regulatory Proteins

Nearly all of biology depends on interactions between molecules: proteins with small molecules, proteins with other proteins, nucleic acids with small molecules, and nucleic acids with proteins that regulate gene expression, our concern in this Special Issue. All those kinds of interactions, and others, constitute the vast majority of biology at the molecular level. An understanding of those interactions requires that we quantify them to learn how they interact: How strongly? With which partners? How—and how well—are different partners distinguished? This review addresses the evolution of our current understanding of the molecular origins of affinity and specificity in regulatory protein–DNA interactions, and suggests that both these properties can be modulated by cooperativity.     

Manipulating Estrogenic/Anti-Estrogenic Activity of Triphenylethylenes towards Development of Novel Anti-Neoplastic SERMs

Selective estrogen receptor modulators (SERMs) act as estrogen receptor (ERα) agonists or antagonists depending on the target issue. Tamoxifen (TAM) (a non-steroidal triphenylethylene derivative) was the first SERM approved as anti-estrogen for the treatment of metastatic breast cancer. On the hunt for novel SERMs with potential growth inhibitory activity on breast cancer cell lines yet no potential to induce endometrial carcinoma, we designed and synthesized 28 novel TAM analogs. The novel analogs bear a triphenylethylene scaffold. Modifications on rings A, B, and C aim to attenuate estrogenic/anti-estrogenic activities of the novel compounds so they can potentially inhibit breast cancer and provide positive, beneficial estrogenic effects on other tissues with no risk of developing endometrial hyperplasia. Compound 12 (E/Z-1-(2-{4-[1-(4-Chloro-phenyl)-2-(4-methoxy-phenyl)-propenyl]-phenoxy}-ethyl)-piperidine) showed an appreciable relative ERα agonistic activity in a yeast estrogen screen (YES) assay. It successfully inhibited the growth of the MCF-7 cell line with GI₅₀ = 0.6 µM, and it was approximately three times more potent than TAM. It showed no potential estrogenicity on Ishikawa endometrial adenocarcinoma cell line via assaying alkaline phosphatase (AlkP) activity. Compound 12 was tested in vivo to assess its estrogenic properties in an uterotrophic assay in an ovariectomized rat model. Compared to TAM, it induced less increase in wet uterine wet weight and showed no uterotrophic effect. Compound 12 is a promising candidate for further development due to its inhibition activity on MCF-7 proliferation with moderate AlkP activity and no potential uterotrophic effects. The in vitro estrogenic activity encourages further investigations toward potential beneficial properties in cardiovascular, bone, and brain tissues.     

Mouse Sertoli Cells Inhibit Humoral-Based Immunity

Transplantation is used to treat many different diseases; however, without the use of immunosuppressants, which can be toxic to the patient, grafted tissue is rejected by the immune system. Humoral immune responses, particularly antibodies and complement, are significant components in rejection. Remarkably, Sertoli cells (SCs), immunoregulatory testicular cells, survive long-term after transplantation without immunosuppression. The objective of this study was to assess SC regulation of these humoral-based immune factors. Mouse SCs survived in vitro human complement (model of robust complement-mediated rejection) and survived in vivo as allografts with little-to-no antibody or complement fragment deposition. Microarray data and ELISA analyses identified at least 14 complement inhibitory proteins expressed by mouse SCs, which inhibit complement at multiple points. Interestingly, a mouse SC line (MSC-1), which was rejected by day 20 post transplantation, also survived in vitro human complement, showed limited deposition of antibodies and complement, and expressed complement inhibitors. Together this suggests that SC inhibition of complement-mediated killing is an important component of SC immune regulation. However, other mechanisms of SC immune modulation are also likely involved in SC graft survival. Identifying the mechanisms that SCs use to achieve extended survival as allografts could be utilized to improve graft survival.     

Transient evolution of weakly nonlinear sloshing waves: an analytical and numerical comparison

The problem of water waves generated in a horizontally oscillating basin is considered, with specific emphasis on the transient evolution of the wave amplitude. A third-order amplitude evolution equation is solved analytically in terms of Jacobian elliptic functions. The solution explicitly determines the maximum amplitude and nonlinear beating period of the resonated wave. An observed bifurcation in the amplitude response is shown to correspond to the elliptic modulus approaching unity and the beating period of the interaction approaching infinity. The theoretical predictions compare favorably to fully nonlinear simulations of the sloshing process. Due to the omission of damping, the consideration of only a single mode, and the weakly nonlinear framework, the analytical solution applies only to finite-depth, non-breaking waves. The inviscid numerical simulations are similarly limited to finite depth.     

Comparison of manual vs. speech-based interaction with in-vehicle information systems

This study examined whether speech-based interfaces for different in-vehicle-information-systems (IVIS) reduce the distraction caused by these systems. For three frequently used systems (audio, telephone with name selection, navigation system with address entry and point of interest selection) speech, manual control and driving without IVIS (baseline) were compared. The Lane Change Task was used to assess driving performance. Additionally, gaze behavior and a subjective measure of distraction were analyzed. Speech interfaces improved driving performance, gaze behavior and subjective distraction for all systems with the exception of point-of-interest entry. However, these improvements were overall not strong enough to reach the baseline performance level. Only in easy segments of the driving task the performance level was comparable to baseline. Thus, speech-based IVIS have to be further developed to keep the cognitive complexity at an adequate level which does not disturb driving. However, looking at the benefits, speech control is a must for the car of the future.     

Flexible Etherified and Esterified Triphenylethylene Derivatives and Their Evaluation on ER-positive and Triple-Negative Breast Cancer Cell Lines

Tamoxifen (TAM) is a selective estrogen receptor modulator (SERM) with potential clinical benefits for all stages of breast cancer. TAM is primarily metabolized to more potent metabolites via polymorphic CYP2D6. This affects the clinical outcome of TAM treatment. Herein we report novel TAM analogues that can avoid metabolism via CYP2D6. The novel analogues bear a flexible skeleton. Compounds have either an ester group on ring C or homodiaminoalkoxy groups on rings B and C . Compound 6 (E/Z-4-[1-[4-(2-diethylaminoethoxy)phenyl]-3-(4-methoxyphenyl)-2-methyl[propenyl]phenol) was found to be ten-fold more potent than TAM on MCF-7 cells (GI₅₀=0.15 μM). It showed fivefold greater inhibitory activity on MDA-MB-231 cells than TAM (GI₅₀=1.71 μM). Compound 13 (4-{3,3-bis-[4-(3-dimethylaminopropoxy)phenyl]-2-methylallyl}methoxybenzene) was the most potent among the homodiaminoalkoxy derivatives (GI₅₀=0.44) on both MCF-7 and MDA-MB-231 cell lines, respectively. Furthermore, the COMPARE algorithm suggested that it has different molecular targets from those of some other reported anticancer drugs.