FAF-Drugs2: Free ADME/tox filtering tool to assist drug discovery and chemical biology projects

<p>Abstract</p> <p>Background</p> <p>Drug discovery and chemical biology are exceedingly complex and demanding enterprises. In recent years there are been increasing awareness about the importance of predicting/optimizing the absorption, distribution, metabolism, excretion and toxicity (ADMET) properties of small chemical compounds along the search process rather than at the final stages. Fast methods for evaluating ADMET properties of small molecules often involve applying a set of simple empirical rules (educated guesses) and as such, compound collections' property profiling can be performed <it>in silico</it>. Clearly, these rules cannot assess the full complexity of the human body but can provide valuable information and assist decision-making.</p> <p>Results</p> <p>This paper presents FAF-Drugs2, a free adaptable tool for ADMET filtering of electronic compound collections. FAF-Drugs2 is a command line utility program (e.g., written in Python) based on the open source chemistry toolkit OpenBabel, which performs various physicochemical calculations, identifies key functional groups, some toxic and unstable molecules/functional groups. In addition to filtered collections, FAF-Drugs2 can provide, via Gnuplot, several distribution diagrams of major physicochemical properties of the screened compound libraries.</p> <p>Conclusion</p> <p>We have developed FAF-Drugs2 to facilitate compound collection preparation, prior to (or after) experimental screening or virtual screening computations. Users can select to apply various filtering thresholds and add rules as needed for a given project. As it stands, FAF-Drugs2 implements numerous filtering rules (23 physicochemical rules and 204 substructure searching rules) that can be easily tuned.</p

A Location Based Value Prediction for Quality of Web Service

The number of web services with functionality increases, the service users usually depends on web recommendation systems. Now a days the service users pay more importance on non functional properties which are also known as Quality of Service (QoS) while finding and selecting appropriate web services. Collaborative filtering approach predicts the QoS values of the web services effectively. Existing recommendation systems rarely consider the personalized influence of the users and services in determining the similarity between users and services. The proposed system is a ranking oriented hybrid approach which integrates user-based and item-based QoS predictions. Many of the non-functional properties depends on the user and the service location. The system thus employs the location information of users and services in selecting similar neighbors for the target user and service and thereby making personalized service recommendation for service users

An Iterative Shrinkage Approach to Total-Variation Image Restoration

The problem of restoration of digital images from their degraded measurements plays a central role in a multitude of practically important applications. A particularly challenging instance of this problem occurs in the case when the degradation phenomenon is modeled by an ill-conditioned operator. In such a case, the presence of noise makes it impossible to recover a valuable approximation of the image of interest without using some a priori information about its properties. Such a priori information is essential for image restoration, rendering it stable and robust to noise. Particularly, if the original image is known to be a piecewise smooth function, one of the standard priors used in this case is defined by the Rudin-Osher-Fatemi model, which results in total variation (TV) based image restoration. The current arsenal of algorithms for TV-based image restoration is vast. In the present paper, a different approach to the solution of the problem is proposed based on the method of iterative shrinkage (aka iterated thresholding). In the proposed method, the TV-based image restoration is performed through a recursive application of two simple procedures, viz. linear filtering and soft thresholding. Therefore, the method can be identified as belonging to the group of first-order algorithms which are efficient in dealing with images of relatively large sizes. Another valuable feature of the proposed method consists in its working directly with the TV functional, rather then with its smoothed versions. Moreover, the method provides a single solution for both isotropic and anisotropic definitions of the TV functional, thereby establishing a useful connection between the two formulae.Comment: The paper was submitted to the IEEE Transactions on Image Processing on October 22nd, 200

Roles of ON cone bipolar cell subtypes in temporal coding in the mouse retina

In the visual system, diverse image processing starts with bipolar cells, which are the second-order neurons of the retina. Thirteen subtypes of bipolar cells have been identified, which are thought to encode different features of image signaling and to initiate distinct signal-processing streams. Although morphologically identified, the functional roles of each bipolar cell subtype in visual signal encoding are not fully understood. Here, we investigated how ON cone bipolar cells of the mouse retina encode diverse temporal image signaling. We recorded bipolar cell voltage changes in response to two different input functions: sinusoidal light and step light stimuli. Temporal tuning in ON cone bipolar cells was diverse and occurred in a subtype-dependent manner. Subtypes 5s and 8 exhibited low-pass filtering property in response to a sinusoidal light stimulus, and responded with sustained fashion to step-light stimulation. Conversely, subtypes 5f, 6, 7, and XBC exhibited bandpass filtering property in response to sinusoidal light stimuli, and responded transiently to step-light stimuli. In particular, subtypes 7 and XBC were high-temporal tuning cells. We recorded responses in different ways to further examine the underlying mechanisms of temporal tuning. Current injection evoked low-pass filtering, whereas light responses in voltage-clamp mode produced bandpass filtering in all ON bipolar cells. These findings suggest that cone photoreceptor inputs shape bandpass filtering in bipolar cells, whereas intrinsic properties of bipolar cells shape low-pass filtering. Together, our results demonstrate that ON bipolar cells encode diverse temporal image signaling in a subtype-dependent manner to initiate temporal visual information-processing pathways

Blind deconvolution of medical ultrasound images: parametric inverse filtering approach

©2007 IEEE. Personal use of this material is permitted. However, permission to reprint/republish this material for advertising or promotional purposes or for creating new collective works for resale or distribution to servers or lists, or to reuse any copyrighted component of this work in other works must be obtained from the IEEE. This material is presented to ensure timely dissemination of scholarly and technical work. Copyright and all rights therein are retained by authors or by other copyright holders. All persons copying this information are expected to adhere to the terms and constraints invoked by each author's copyright. In most cases, these works may not be reposted without the explicit permission of the copyright holder.DOI: 10.1109/TIP.2007.910179The problem of reconstruction of ultrasound images by means of blind deconvolution has long been recognized as one of the central problems in medical ultrasound imaging. In this paper, this problem is addressed via proposing a blind deconvolution method which is innovative in several ways. In particular, the method is based on parametric inverse filtering, whose parameters are optimized using two-stage processing. At the first stage, some partial information on the point spread function is recovered. Subsequently, this information is used to explicitly constrain the spectral shape of the inverse filter. From this perspective, the proposed methodology can be viewed as a ldquohybridizationrdquo of two standard strategies in blind deconvolution, which are based on either concurrent or successive estimation of the point spread function and the image of interest. Moreover, evidence is provided that the ldquohybridrdquo approach can outperform the standard ones in a number of important practical cases. Additionally, the present study introduces a different approach to parameterizing the inverse filter. Specifically, we propose to model the inverse transfer function as a member of a principal shift-invariant subspace. It is shown that such a parameterization results in considerably more stable reconstructions as compared to standard parameterization methods. Finally, it is shown how the inverse filters designed in this way can be used to deconvolve the images in a nonblind manner so as to further improve their quality. The usefulness and practicability of all the introduced innovations are proven in a series of both in silico and in vivo experiments. Finally, it is shown that the proposed deconvolution algorithms are capable of improving the resolution of ultrasound images by factors of 2.24 or 6.52 (as judged by the autocorrelation criterion) depending on the type of regularization method used