Complementary Dual Approach for In Silico Target Identification of Potential Pharmaceutical Compounds in Cystic Fibrosis

Cystic fibrosis is a genetic disease caused by mutation of the CFTR gene, which encodes a chloride and bicarbonate transporter in epithelial cells. Due to the vast range of geno- and phenotypes, it is difficult to find causative treatments; however, small-molecule therapeutics have been clinically approved in the last decade. Still, the search for novel therapeutics is ongoing, and thousands of compounds are being tested in different assays, often leaving their mechanism of action unknown. Here, we bring together a CFTR-specific compound database (CandActCFTR) and systems biology model (CFTR Lifecycle Map) to identify the targets of the most promising compounds. We use a dual inverse screening approach, where we employ target- and ligand-based methods to suggest targets of 309 active compounds in the database amongst 90 protein targets from the systems biology model. Overall, we identified 1038 potential target–compound pairings and were able to suggest targets for all 309 active compounds in the database.     

Gender differences in sexual abuse outcomes and recovery experiences: A survey of therapist-survivors.

If gender differences in recovery from childhood sexual abuse (CSA) go unrecognized, treatment may be unsuccessful. Gender differences in abuse characteristics, outcomes, and recovery are described for 131 therapists with CSA histories. Female clinicians reported more problems with self-esteem relationships, trust, sex, and work than males. Female clinicians identified several recovery experiences as more important: relinquishing guilt, talking about the abuse, renegotiating family-of-origin relationships, personal therapy, reading or writing about their CSA, hospitalization, and CSA workshops. Therapists working with male victims need to be aware of possible gender differences in symptom report and effects of healing strategies. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

It's All About Getting What You Want What We Want Is to Make Work That Fits

Today we live in a culture of institutionalised public realm – it is not the grass-roots activity of the 1970s. However, Liza Fior, Katherine Clarke and Sophie Handler of muf architecture explain how the collaborative nature of the practice, both internally and in its approach to any project brief, defines how, today, a community is as strong as the questions it is prepared to ask of itself. Copyright © 2005 John Wiley & Sons, Ltd.     

Impact of a clinician's sexual abuse history, gender, and theoretical orientation on treatment issues related to childhood sexual abuse.

This study examined the impact of childhood sexual abuse history (CSA), gender, and theoretical orientation on treatment issues related to childhood sexual abuse. A survey of 501 clinicians found that 32% reported CSA histories. Sexually abused therapists were more likely to report some countertransference issues, especially boundary issues, than nonabused therapists, but gender differences were more important in determining differences in clinical practice. Female clinicians reported that CSA was more difficult to treat, that they screened more regularly for CSA, and that they utilized more coping strategies than male clinicians. Dissimilarities were also found between self-identified feminist therapists and psychoanalysts in their clinical practices, including the use of personality disorder diagnoses, reported countertransference issues, and coping strategies. Greater recognition of these issues in training programs is recommended. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

CFTR Lifecycle Map—A Systems Medicine Model of CFTR Maturation to Predict Possible Active Compound Combinations

Different causative therapeutics for CF patients have been developed. There are still no mutation-specific therapeutics for some patients, especially those with rare CFTR mutations. For this purpose, high-throughput screens have been performed which result in various candidate compounds, with mostly unclear modes of action. In order to elucidate the mechanism of action for promising candidate substances and to be able to predict possible synergistic effects of substance combinations, we used a systems biology approach to create a model of the CFTR maturation pathway in cells in a standardized, human- and machine-readable format. It is composed of a core map, manually curated from small-scale experiments in human cells, and a coarse map including interactors identified in large-scale efforts. The manually curated core map includes 170 different molecular entities and 156 reactions from 221 publications. The coarse map encompasses 1384 unique proteins from four publications. The overlap between the two data sources amounts to 46 proteins. The CFTR Lifecycle Map can be used to support the identification of potential targets inside the cell and elucidate the mode of action for candidate substances. It thereby provides a backbone to structure available data as well as a tool to develop hypotheses regarding novel therapeutics.     

Multiple-jet electrospinning methods for nanofiber processing: A review

Electrospinning is a versatile method of producing continuous nanofibers through the application of an electric field. The simplest and earliest form of electrospinning involves the use of a single-needle spinneret to draw the solution out and form fibers. The process, however, is very time consuming, limiting the potential wide-scale application of electrospun nanofibers. Many multiple-jet electrospinning methods have been proposed to overcome the problem of low productivity, but the generation of multiple jets brought about other problems such as jet repulsion, lower process controllability, and deterioration of fiber quality. Thus, continuous development is necessary for the optimization of the process. The aim of this review is to provide an overview of the recent electrospinning technologies reported in the literature, particularly on various multiple-jet electrospinning methods from both nozzles and free surfaces. The general principle underlying the electrospinning process, as well as important parameters involved are also presented in this paper.     

Assessment of PM dry deposition on solar energy harvesting systems: Measurement–model comparison

Soiling of solar energy systems, or the accumulation of particulate matter on their surface, can cause significant losses in energy conversion efficiency. However, predicting these losses is still not done, as no methods exist. Field measurements of mass accumulation and airborne PM₁₀ were conducted for more than one year at two sites in the Front Range of Colorado with the objective of developing soiling prediction models. For this study, only dry deposition was examined. The two sites, despite having different PM₁₀ concentrations, have indistinguishable average effective deposition velocities of 2 cm/s, although a large spread in the data was noted. These results are similar to results found in other deposition studies. The observed effective deposition velocities indicate that coarse particles are a dominant player in mass accumulation, and sampled airborne size distributions support this hypothesis. Using a model to calculate dry deposition yielded better agreement with deposition than a simple average deposition velocity data fit. This model combined with other research and models can be used for estimating average soiling rates and is most useful over long time scales especially months to years or longer.

Copyright © 2016 American Association for Aerosol Research     

The effect of frying on browning,acrylamide and 5-hydroxymethylfurfural formation on Malaysian curry puff skin treated with l-asparaginase

Food Science and Biotechnology - Acrylamide and 5-hydroxymethylfurfural (HMF) is the product of the Maillard reaction and its accumulation may lead to adverse health effects. Hence, this paper aims...     

Endosperm and whole grain rye breads are characterized by low post-prandial insulin response and a beneficial blood glucose profile

Background  

Rye products have previously been shown to induce comparatively low post-prandial insulin responses; irrespectively of their glycaemic indices (GI). However, the mechanism behind this lowered insulin demand remains unknown. An improved insulin economy might contribute to the benefits seen in epidemiological studies with whole grain diets on metabolic risk factors and weight regulation. The objective of this study was to explore the mechanism for a reduced post-prandial insulin demand with rye products.     

A Model-Integrated, Guideline-Driven, Clinical Decision-Support System

Using evidence-based guidelines to standardize the care of patients with complex medical problems is a difficult challenge. In acute care settings, such as intensive care units, the inherent problems of stabilizing and improving vital patient parameters is complicated by the division of responsibilities among different healthcare team members. Computerized support for implementing such guidelines has tremendous potential. The use of model-integrated techniques for specifying and implementing guidelines as coordinated asynchronous processes is a promising new methodology for providing advanced clinical decision support. Combined with visual dashboards, which show the status of the implemented guidelines, a new approach to computer-supported care is possible. The Vanderbilt Medical Center is applying these techniques to the management of sepsis.