Non-transferrin iron uptake by trophoblast cells in culture. Significance of a NADH-dependent ferrireductase

BACKGROUND: Glucocorticoids have been linked to self-administration of a wide range of drugs in animals and are increased endogenously by chronic nicotine intake. Corticosteroids have also been shown to regulate nicotine receptor sensitivity and to be involved in behavioral sensitization to nicotine. METHODS: Cortisol levels and cortisol suppression in response to dexamethasone were measured in a sample of smokers participating in a smoking cessation treatment trial. RESULTS: Cortisol levels dropped significantly during the early quitting process (2 weeks post-quit) and returned to a level below baseline 1 month post-quit. The magnitude of the initial drop in cortisol was strongly related to post-quit distress and marginally predictive of abstinence. Neither baseline nor post-quit changes in percent cortisol suppression after dexamethasone were related to abstinence success or withdrawal distress. CONCLUSIONS: Withdrawal from cigarette smoking is marked by a reduction in cortisol levels that appears to be related to the degree of distress experienced during the early quitting period. Further work is needed to determine whether withdrawal-related cortisol changes or distress are predictive of abstinence success.     

Ethical and practical issues involved in behavioral pharmacology research that administers drugs of abuse to human volunteers

Researchers carrying out non-therapeutic research that involves the administration of drugs of abuse to human volunteers can be faced with many ethical and practical questions. The history of this type of research is relatively brief, with little in the way of published information relevant to carrying out behavioral pharmacological research with human participants. The aim of this article is to raise issues that occur in most studies of this type and to provide solutions that we have found acceptable and which have been approved by a variety of institutions and regulatory agencies. Clearly, there are other approaches that would work equally as well, and we are not attempting to provide 'the' answer to many of the issues raised. We believe that raising these issues and providing our perspectives is important for stimulating others to discuss them and for all of us to strive, where possible, to reach a consensus concerning ethical practices and to become aware of gaps and pitfalls. The topics discussed range from the nuts and bolts of acquiring and keeping track of drugs, to selecting research participants and designing ethical studies that protect our volunteers while still collecting scientifically useful data.     

The Drug Evaluation Classification Program: using ocular and other signs to detect drug intoxication

BACKGROUND: A systematic approach to determining drug intoxication has been developed for use by police officers. By considering specific physiological signs, trained officers can detect the effects of seven major drug types. METHODS: Officers follow a 12-step testing sequence and evaluate signs such as pupil sizes and responses, eye movements, heart rate, body temperature, mental timing, and balance. A matrix is then used to compare that subject's signs to those that would be produced by the seven types of drugs. If a pattern match is found, the officer concludes that the subject is under the influence of a drug and specifies the drug type. RESULTS: Several field and laboratory validation studies have been conducted using these procedures. In general, officers were 70% to 90% accurate in determining intoxication status and drug classification, but poly-drug use and drug rebound effects can sometimes cause problems in interpretation. CONCLUSION: Ocular and other physiological signs can be used to detect drug intoxication and classify the type of drug taken. Knowledge of the procedures used in the Drug Recognition Program can enable optometrists to serve as consultants to the police and as expert witnesses in cases involving the use of ocular signs that indicate illicit drug use.     

Recruitment strategies in the women's health trial: feasibility study in minority populations. WHT:FSMP Investigators Group. Women's Health Trial:Feasibility Study in Minority Populations

The Women's Health Trial:Feasibility Study in Minority Populations (WHT:FSMP) examined the feasibility of recruiting postmenopausal women from a broad range of racial and socioeconomic backgrounds into a primary prevention trial requiring marked reductions in dietary fat. Postmenopausal women aged 50-79 yr who had no history of cardiovascular disease or cancer and who consumed 36% or more total energy from fat qualified to participate. We randomized the women into dietary intervention (60%) or control (40%) groups; we aimed to randomize 750 women in 18 months in each of the three clinical centers. All centers achieved goals for randomization based on ethnicity, and two centers exceeded overall recruitment goals. The greatest source of randomized participants was mass mailing, followed by items in the media, referrals, and community outreach. Recruitment yields were generally similar for the ethnic groups but lower for less-educated participants. The experience of WHT:FSMP indicates that postmenopausal women from the African-American, Hispanic, and non-Hispanic white communities can be recruited into dietary intervention studies for the prevention of disease.     

Long-term information collection with energy harvesting wireless sensors: a multi-armed bandit based approach

This paper reports on the development of a multi-agent approach to long-term information collection in networks of energy harvesting wireless sensors. In particular, we focus on developing energy management and data routing policies that adapt their behaviour according to the energy that is harvested, in order to maximise the amount of information collected given the available energy budget. In so doing, we introduce a new energy management technique, based on multi-armed bandit learning, that allows each agent to adaptively allocate its energy budget across the tasks of data sampling, receiving and transmitting. By using this approach, each agent can learn the optimal energy budget settings that give it efficient information collection in the long run. Then, we propose two novel decentralised multi-hop algorithms for data routing. The first proveably maximises the information throughput in the network, but can sometimes involve high communication cost. The second algorithm provides near-optimal performance, but with reduced computational and communication costs. Finally, we demonstrate that, by using our approaches for energy management and routing, we can achieve a 120% improvement in long-term information collection against state-of-the-art benchmarks.     

Thrombospondin-1 CD47 Signalling: From Mechanisms to Medicine

Recent advances provide evidence that the cellular signalling pathway comprising the ligand-receptor duo of thrombospondin-1 (TSP1) and CD47 is involved in mediating a range of diseases affecting renal, vascular, and metabolic function, as well as cancer. In several instances, research has barely progressed past pre-clinical animal models of disease and early phase 1 clinical trials, while for cancers, anti-CD47 therapy has emerged from phase 2 clinical trials in humans as a crucial adjuvant therapeutic agent. This has important implications for interventions that seek to capitalize on targeting this pathway in diseases where TSP1 and/or CD47 play a role. Despite substantial progress made in our understanding of this pathway in malignant and cardiovascular disease, knowledge and translational gaps remain regarding the role of this pathway in kidney and metabolic diseases, limiting identification of putative drug targets and development of effective treatments. This review considers recent advances reported in the field of TSP1-CD47 signalling, focusing on several aspects including enzymatic production, receptor function, interacting partners, localization of signalling, matrix-cellular and cell-to-cell cross talk. The potential impact that these newly described mechanisms have on health, with a particular focus on renal and metabolic disease, is also discussed.     

HEAT TRANSFER BETWEEN ROUGH SURFACES IN CONTACT OVER A HIGHLY ELLIPTICAL CONTOUR AREA: COMPARISON OF EXPERIMENTAL AND NUMERICAL RESULTS

This paper describes experimental and numerical studies of heat transfer between surfaces in contact over a highly elliptical area in a gas or in vacuum. Measurements of the steady-state thermal resistance of a high aspect ratio contact formed between cylindrical steel surfaces with widely different radii of curvature (76 cm vs 0.95 cm) are reported for two levels of surface roughness (0.05 μm and 1.0 μm rms) and compared to 3-D numerical results obtained with the multigrid method. Theoretical results obtained by evaluating the contact conductance acting over each surface element within the contour area with a method developed previously for rough but nominally flat surfaces are shown to be in excellent agreement with the rough surface experimental data.     

Stability of nonlinear 2D systems described by the continuous-time Roesser model

This paper considers systems with two-dimensional dynamics (2D systems) described by the continuous-time nonlinear state-space Roesser model. The sufficient conditions of exponential stability in terms of vector Lyapunov functions are established. These conditions are then applied to analysis of the absolute stability of a certain class of systems comprising a linear continuous-time plant in the form of the Roesser model with a nonlinear characteristic in the feedback loop, which satisfies quadratic constraints. The absolute stability conditions are reduced to computable expressions in the form of linear matrix inequalities. The obtained results are extended to the class of continuous-time systems governed by the Roesser model with Markovian switching. The problems of absolute stability and stabilization via state- and output-feedback are solved for linear systems of the above class. The solution procedures for these problems are in the form of algorithms based on linear matrix inequalities.     

Dis-Bond Detection and the Possibility of Interfacial Stiffness Measurement with Real-Time Impulsive Stimulated Thermal Scattering

We describe a new, real-time, noninvasive method for dis-bond (delamination) detection which is based on a technique known as impulsive stimulated thermal scattering (ISTS). We first explain the ISTS technique and compare data from polyimide films tightly bound to silicon substrates with data from unsupported polyimide films. The observed differences in the data from these two cases are readily understandable and offer an unmistakable signature for delaminations. We demonstrate ISTS dis-bond detection by locating and mapping out randomly-distributed and spatially-fine regions of delamination in a polyimide film-silicon substrate system. Finally, we present two simple physical models of the interfacial region which comprehensively describe acoustic data from the tightly-bound and the unsupported samples. With insight from simulations using these models, we suggest how ISTS might be used to determine interfacial adhesion quality and we show how ISTS sensitivity to interfacial effects can be adjusted.