PubChem: a public information system for analyzing bioactivities of small molecules

PubChem (http://pubchem.ncbi.nlm.nih.gov) is a public repository for biological properties of small molecules hosted by the US National Institutes of Health (NIH). PubChem BioAssay database currently contains biological test results for more than 700 000 compounds. The goal of PubChem is to make this information easily accessible to biomedical researchers. In this work, we present a set of web servers to facilitate and optimize the utility of biological activity information within PubChem. These web-based services provide tools for rapid data retrieval, integration and comparison of biological screening results, exploratory structure–activity analysis, and target selectivity examination. This article reviews these bioactivity analysis tools and discusses their uses. Most of the tools described in this work can be directly accessed at http://pubchem.ncbi.nlm.nih.gov/assay/. URLs for accessing other tools described in this work are specified individually

Étude de l'absorption des phosphates, azote, chrome et cadmium par trois algues vertes isolées à partir d'effluents urbains

La capacité de déphosphatation et de dénitrification ainsi que la sensibilité et l'accumulation de deux métaux lourds (Cr et Cd) de Scenedesmus quadricauda, Chlorella pyrenoidosa et Chlamydomonas reinhardtii isolées des eaux usées de la ville de Fès, ont été étudiées dans les conditions de laboratoire. Les résultats ont montré que S. quadricauda présente les meilleurs taux de réduction des phosphates (83%), et d'ammonium (75%). L'étude de la sensibilité vis à vis du chrome et du cadmium des trois espèces, a montré qu'au delà d'une concentration de 1 ppm, la croissance se trouve réduite et que S. quadricauda présente une sensibilité plus faible que les deux autres espèces. Les résultats des expériences d'absorption conduites avec du chrome VI marqué au51 Cr et du cadmium marqué au109 Cd ont montré que les quantités de chrome et du cadmium prélevées par S. quadricauda dépassent celles des deux autres espèces. L'utilisation potentielle des trois espèces dans le traitement des effluents urbains est discutée à la lumière des résultats de ces expériences.Wastewater discharge is an environmental problem, especially in developing countries. Biological wastewater treatment seems to be an alternative for these countries due to its low cost. Algae are used in such wastewater treatment systems in many parts of the world. In addition to preventing environmental damage, the reuse of treated wastewater can be an alternative water supply in arid regions and during drought periods.In this paper, three algal (Chlamydomonas reinhardtii, Chlorella pyrenoïdosa and Scenedesmus quadricauda) species were isolated from an urban effluent collected from a Mediterranean city (Fez, Morocco, situated between 4° to 7° W and 33° to 35° N) and their ability to remove phosphate and nitrogen was tested under laboratory conditions. The toxicity and uptake of chromium and cadmium were also studied.Fez city wastewater was sampled monthly during one year (2000) at three main stations located along the Boukhrareb stream which crosses the city. The following parameters were measured according to methods described by RODIER J. (1996): Chemical oxygen demand, COD; Biological oxygen demand, BOD; NO3 -; NH4 +; PO43 -; electrical conductivity (EC) and organic matter. Heavy metals (Cr, Fe and Zn) were measured by INAA (Instrumental Thermal Neutron Activation Analysis) in wastewater samples dried on Teflon sheets at 70°C.The collected samples were incubated under controlled conditions and species of alga were identified, isolated, and then transferred to fresh culture medium. Chlamydomonas reinhardtii, Chlorella pyrenoïdosa and Scenedesmus quadricauda were chosen for these experiments because of their abundance in wastewater over the year and for their capacities for biomass production. The removal of nutrients from aqueous media was studied by using monospecific cultures. Algae were in the exponential growth phase when the experiments were started and BG11 culture medium was used under standard growth conditions. Initial concentrations of phosphate and nitrogen were 2.24 mg×L-1 (PO43 -), 12.84 mg×L-1 (NO3 -) and 0.26 mg×L-1 (N-NH4 +). The concentrations decreased during the experimental period, and degrees of removal ranged from 83 to 75% for phosphate, from 85 to 77% for nitrogen and from 52 to 75% for ammonium.To evaluate the sensitivity of the algal cells to heavy metals, the algal strains were exposed for one week to chromium as K2Cr2O7 and cadmium as CdCl2 at concentrations of 0.1, 0.5, 1, 1.5 and 2 ppm (mg×L-1) of Cr or Cd. Culture growth was monitored by microscopic counting of algal cells to determine quantitative biomass changes. Results demonstrated that growth inhibition occurred at 1 ppm Cr and Cd, whereas levels of 1.5 and 2 ppm of both metals were lethal to the cultures, but no effect on growth was seen in algae exposed to 0.1 ppm of Cd or 0.1 ppm of Cr. Scenedesmus quadricauda was more resistant than Chlamydomonas reinhardtii and Chlorella pyrenoïdosa to chromium and cadmium.Radiotracers (51Cr and 109Cd) were used to trace the biosorption of chromium and cadmium by the three algal strains. Cr(VI) as K2 Cr2O7 and Cd as CdCl2 were added to the algal suspension culture to give concentrations of 1, 1.5 and 2 ppm Cd and Cr respectively. At various stages during growth of the unialgal cultures, samples were removed, a pulse of51 Cr or109 Cd was added, and the uptake rates of Cr(VI) and Cd were determined. To evaluate the amount of heavy metals removed by the algal cells, microscopic cell counting was carried out. All the experiments were conducted under the above-mentioned conditions for each concentration studied, the measurements were repeated three times and the mean values from the three replicates were calculated. The results showed that chromium and cadmium removal by algae was dependent on the metal concentration in the culture medium. The quantity of metal removed also varied with algal species, where 20 µg, 23 µg and 35 µg of Cd were accumulated by 106 cells of Chlorella, Chlamydomonas and Scenedesmus respectively at a metal concentration of 2 ppm. About 25 µg of Cr were accumulated by 106 cells of Chlorella and Chlamydomonas whereas, 106 cells of Scenedesmus accumulated 32 µg of Cr at a concentration of 2 ppm.The experimental data presented here demonstrated that there was not a great difference in the uptake capabilities between the three algal strains, and reaffirmed the potential of algae in the purification of metal-contaminated wastewater. This wastewater treatment system has many advantages and it is an efficient way to significantly reduce the release of nutrients (e.g., phosphorus, nitrogen, ammonia) and heavy metals (e.g., chromium and cadmium)

The impact of greyscale inversion for nodule detection in an anthropomorphic chest phantom: a free-response observer study

Objective: The aim of this work was to assess the impact of greyscale inversion on nodule detection on poster- oanterior chest X-ray images. Previous work has attemp- ted this, with no consensus opinion formed. We assessed the value of “fast-flicking” between standard and inverted display modes for nodule detection. Methods: Six consultant radiologists (with 5–32 years’ reporting experience) completed an observer task under the free-response paradigm. An anthropomorphic chest phantom was loaded with 50 different configurations of simulated nodules (1–4 nodules per case) measuring 5, 8, 10 and 12mm in spherical diameter; each configuration represented a single case. In addition, 25 cases contained no nodules. Images were displayed in three modes: (i) standard, (ii) inverted and (iii) fast-flicking between standard and inverted display modes. Each observer completed the study in a different order of display (i, ii, iii) using a calibrated 5-megapixel monitor. Nodules were localized with mouse clicks and ratings assigned using a 1–10 discrete slider-bar confidence scale. Rjafroc (Pitts- burgh, PA) was used for data analysis; differences in nodule detection performance were considered significant at 0.05. Results: The observer-averaged weighted jackknife alter- native free-response receiver-operating characteristic figures of merit were 0.715 (standard), 0.684 (inverted) and 0.717 (fast-flicking). Random-reader fixed-case anal- ysis revealed no statistically significant difference be- tween any treatment pair [F(2,8) 5 1.22; p 5 0.345]. Conclusion: No statistically significant difference in nodule detection was found for the three display conditions. Advances in knowledge: We have investigated the impact of fast-flicking between standard and inverted display modes for the detection of nodules. We found no benefit

The Role of Quantitative Pharmacology in an Academic Translational Research Environment

Translational research is generally described as the application of basic science discoveries to the treatment or prevention of disease or injury. Its value is usually determined based on the likelihood that exploratory or developmental research can yield effective therapies. While the pharmaceutical industry has evolved into a highly specialized sector engaged in translational research, the academic medical research community has similarly embraced this paradigm largely through the motivation of the National Institute of Health (NIH) via its Roadmap initiative. The Clinical and Translational Science Award (CTSA) has created opportunities for institutions which can provide the multidisciplinary environment required to engage such research. A key component of the CTSA and an element of both the NIH Roadmap and the FDA Critical Path is the bridging of bench and bedside science via quantitative pharmacologic relationships. The infrastructure of the University of Pennsylvania/Children’s Hospital of Philadelphia CTSA is highlighted relative to both research and educational objectives reliant upon quantitative pharmacology. A case study, NIH-sponsored research program exploring NK1r antagonism for the treatment NeuroAIDS is used to illustrate the application of quantitative pharmacology in a translational research paradigm

The status of clinical trials: Cause for concern

<p>Abstract</p> <p>Background</p> <p>Americans see clinical research as important, with over 15 million American residents participating in NIH-sponsored studies in 2008 and growing yearly.</p> <p>Methods</p> <p>Documents reporting NIH supported Clinical Research projects were reviewed.</p> <p>Results</p> <p>When compared with other studies, the number of interventional Phase III and Phase IV trials have decreased from 20% to 4.4% from 1994-2008.</p> <p>Conclusions</p> <p>This finding most likely has occurred for several reasons. One reason is that the physician lacks an infrastructure for designing and carrying out trials. This lack is because of an absence of a coordinated effort to train clinical trialists. It is clear that the Nation needs a more purposeful approach to developing and maintaining the infrastructure for designing and conducting clinical trials. Building it de novo trial by trial is profoundly inefficient, to say nothing about time consuming and error prone.</p

Quantitative CT of lung nodules: Dependence of calibration on patient body size, anatomic region, and calibration nodule size for singleâ and dualâ energy techniques

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/134901/1/mp8536.pd

Collaborative research between clinicians and researchers: a multiple case study of implementation

<p>Abstract</p> <p>Background</p> <p>Bottom-up, clinician-conceived and directed clinical intervention research, coupled with collaboration from researcher experts, is conceptually endorsed by the participatory research movement. This report presents the findings of an evaluation of a program in the Veterans Health Administration meant to encourage clinician-driven research by providing resources believed to be critical. The evaluation focused on the extent to which funded projects: maintained integrity to their original proposals; were methodologically rigorous; were characterized by collaboration between partners; and resulted in sustained clinical impact.</p> <p>Methods</p> <p>Researchers used quantitative (survey and archival) and qualitative (focus group) data to evaluate the implementation, evaluation, and sustainability of four clinical demonstration projects at four sites. Fourteen research center mentors and seventeen clinician researchers evaluated the level of collaboration using a six-dimensional model of participatory research.</p> <p>Results</p> <p>Results yielded mixed findings. Qualitative and quantitative data suggested that although the process was collaborative, clinicians' prior research experience was critical to the quality of the projects. Several challenges were common across sites, including subject recruitment, administrative support and logistics, and subsequent dissemination. Only one intervention achieved lasting clinical effect beyond the active project period. Qualitative analyses identified barriers and facilitators and suggested areas to improve sustainability.</p> <p>Conclusions</p> <p>Evaluation results suggest that this participatory research venture was successful in achieving clinician-directed collaboration, but did not produce sustainable interventions due to such implementation problems as lack of resources and administrative support.</p

The relationship between gambling advertising and gambling attitudes, intentions and behaviours:a critical and meta-analytic review

Gambling advertising has become ubiquitous in westernised countries in the last two decades, yet there is little understanding of the relationship between exposure to gambling advertising and gambling attitudes, intentions and behaviour. We conduct a critical and meta-analytic review of the past two decades of empirical research. The research suggests a positive association between exposure to gambling advertising and gambling-related attitudes, intentions and behaviour. The association is greatest for gambling behaviour. There is some evidence for a dose-response relationship. The quality and breadth of research on gambling advertising are weaker than those in comparable areas (e.g., alcohol, tobacco), with an absence of longitudinal and experimental studies. Gaps in, and methodological problems with, the field are discussed, and research directions recommended

Routes for breaching and protecting genetic privacy

We are entering the era of ubiquitous genetic information for research, clinical care, and personal curiosity. Sharing these datasets is vital for rapid progress in understanding the genetic basis of human diseases. However, one growing concern is the ability to protect the genetic privacy of the data originators. Here, we technically map threats to genetic privacy and discuss potential mitigation strategies for privacy-preserving dissemination of genetic data.Comment: Draft for comment