A gradient descent algorithm for minimizing amino acid coupling reactions when synthesizing cyclic-peptide libraries

Combinatorial chemistry has become an invaluable tool in medicinal chemistry for the identification of new drug leads. For example, libraries of predetermined sequences and head-to-tail cyclized peptides are routinely synthesized in our laboratory using the IRORI approach. Such libraries are used as molecular toolkits that enable the development of pharmacophores that define activity and specificity at receptor targets. These libraries can be quite large and difficult to handle, due to physical and chemical constraints imposed by their size. Therefore, smaller sub-libraries are often targeted for synthesis. The number of coupling reactions required can be greatly reduced if the peptides having common amino acids are grouped into the same sub-library (batching). This paper describes a schedule optimizer to minimize the number of coupling reactions by rotating and aligning sequences while simultaneously batching. The gradient descent method thereby reduces the number of coupling reactions required for synthesizing cyclic peptide libraries. We show that the algorithm results in a 75% reduction in the number of coupling reactions for a typical cyclic peptide library.

A New Gradient Descent Approach for Local Learning of Fuzzy Neural Models

The majority of reported learning methods for Takagi-Sugeno-Kang fuzzy neural models to date mainly focus on the improvement of their accuracy. However, one of the key design requirements in building an interpretable fuzzy model is that each obtained rule consequent must match well with the system local behaviour when all the rules are aggregated to produce the overall system output. This is one of the distinctive characteristics from black-box models such as neural networks. Therefore, how to find a desirable set of fuzzy partitions and, hence, to identify the corresponding consequent models which can be directly explained in terms of system behaviour presents a critical step in fuzzy neural modelling. In this paper, a new learning approach considering both nonlinear parameters in the rule premises and linear parameters in the rule consequents is proposed. Unlike the conventional two-stage optimization procedure widely practised in the field where the two sets of parameters are optimized separately, the consequent parameters are transformed into a dependent set on the premise parameters, thereby enabling the introduction of a new integrated gradient descent learning approach. A new Jacobian matrix is thus proposed and efficiently computed to achieve a more accurate approximation of the cost function by using the second-order Levenberg-Marquardt optimization method. Several other interpretability issues about the fuzzy neural model are also discussed and integrated into this new learning approach. Numerical examples are presented to illustrate the resultant structure of the fuzzy neural models and the effectiveness of the proposed new algorithm, and compared with the results from some well-known methods.

Adaptive online gradient descent

We study the rates of growth of the regret in online convex optimization. First, we show that a simple extension of the algorithm of Hazan et al eliminates the need for a priori knowledge of the lower bound on the second derivatives of the observed functions. We then provide an algorithm, Adaptive Online Gradient Descent, which interpolates between the results of Zinkevich for linear functions and of Hazan et al for strongly convex functions, achieving intermediate rates between [square root T] and [log T]. Furthermore, we show strong optimality of the algorithm. Finally, we provide an extension of our results to general norms.

Adaptive online gradient descent

We study the rates of growth of the regret in online convex optimization. First, we show that a simple extension of the algorithm of Hazan et al eliminates the need for a priori knowledge of the lower bound on the second derivatives of the observed functions. We then provide an algorithm, Adaptive Online Gradient Descent, which interpolates between the results of Zinkevich for linear functions and of Hazan et al for strongly convex functions, achieving intermediate rates between [square root T] and [log T]. Furthermore, we show strong optimality of the algorithm. Finally, we provide an extension of our results to general norms.

A sequential dual method for structural SVMs

In many real world prediction problems the output is a structured object like a sequence or a tree or a graph. Such problems range from natural language processing to compu- tational biology or computer vision and have been tackled using algorithms, referred to as structured output learning algorithms. We consider the problem of structured classifi- cation. In the last few years, large margin classifiers like sup-port vector machines (SVMs) have shown much promise for structured output learning. The related optimization prob -lem is a convex quadratic program (QP) with a large num-ber of constraints, which makes the problem intractable for large data sets. This paper proposes a fast sequential dual method (SDM) for structural SVMs. The method makes re-peated passes over the training set and optimizes the dual variables associated with one example at a time. The use of additional heuristics makes the proposed method more efficient. We present an extensive empirical evaluation of the proposed method on several sequence learning problems.Our experiments on large data sets demonstrate that the proposed method is an order of magnitude faster than state of the art methods like cutting-plane method and stochastic gradient descent method (SGD). Further, SDM reaches steady state generalization performance faster than the SGD method. The proposed SDM is thus a useful alternative for large scale structured output learning.

Differentially private stochastic gradient descent algorithm for multiparty classification

We consider the problem of developing privacy-preserving machine learning algorithms in a dis-tributed multiparty setting. Here different parties own different parts of a data set, and the goal is to learn a classifier from the entire data set with-out any party revealing any information about the individual data points it owns. Pathak et al [7]recently proposed a solution to this problem in which each party learns a local classifier from its own data, and a third party then aggregates these classifiers in a privacy-preserving manner using a cryptographic scheme. The generaliza-tion performance of their algorithm is sensitive to the number of parties and the relative frac-tions of data owned by the different parties. In this paper, we describe a new differentially pri-vate algorithm for the multiparty setting that uses a stochastic gradient descent based procedure to directly optimize the overall multiparty ob-jective rather than combining classifiers learned from optimizing local objectives. The algorithm achieves a slightly weaker form of differential privacy than that of [7], but provides improved generalization guarantees that do not depend on the number of parties or the relative sizes of the individual data sets. Experimental results corrob-orate our theoretical findings.

Application of the gradient boosted method in randomised clinical trials: participant variables that contribute to depression treatment efficacy of duloxetine, SSRIs or placebo

Randomised, placebo-controlled trials of treatments for depression typically collect outcomes data but traditionally only analyse data to demonstrate efficacy and safety. Additional post-hoc statistical techniques may reveal important insights about treatment variables useful when considering inter-individual differences amongst depressed patients. This paper aims to examine the Gradient Boosted Model (GBM), a statistical technique that uses regression tree analyses and can be applied to clinical trial data to identify and measure variables that may influence treatment outcomes.

A Gradient-Type Method For Real-Time State Estimation Of Water Distribution Networks

Drinking water distribution networks risk exposure to malicious or accidental contamination. Several levels of responses are conceivable. One of them consists to install a sensor network to monitor the system on real time. Once a contamination has been detected, this is also important to take appropriate counter-measures. In the SMaRT-OnlineWDN project, this relies on modeling to predict both hydraulics and water quality. An online model use makes identification of the contaminant source and simulation of the contaminated area possible. The objective of this paper is to present SMaRT-OnlineWDN experience and research results for hydraulic state estimation with sampling frequency of few minutes. A least squares problem with bound constraints is formulated to adjust demand class coefficient to best fit the observed values at a given time. The criterion is a Huber function to limit the influence of outliers. A Tikhonov regularization is introduced for consideration of prior information on the parameter vector. Then the Levenberg-Marquardt algorithm is applied that use derivative information for limiting the number of iterations. Confidence intervals for the state prediction are also given. The results are presented and discussed on real networks in France and Germany.

Rapid determination of zinc in foods by flow injection analysis with flame AAS using gradient calibration method

A calibration method was developed using flow injection analysis (FI) with a Gradient Calibration Method (GCM). The method allows the rapid determination of zinc In foods (approximately 30 min) after treatment with concentrated sulphuric acid and 30% hydrogen peroxide, and analysis with flame atomic absorption spectrometry (FAAS). The method provides analytical results with a relative standard deviation of about 2% and requires less time than by conventional FI calibration. The electronic selection of different segments along the gradient and monitoring of the technique covers wide concentration ranges while maintaining the inherent high precision of flow injection analysis. Concentrations, flow rates, and flow times of the reagents were optimized in order to obtain best accuracy and precision. Flow rates of 10 mL/min were selected for zinc. In addition, the system enables electronic dilution and calibration where a multipoint curve can be constructed using a single sample injection.

Particle tracking in a salinity gradient: A method for measuring sinking rate of individual phytoplankton in the laboratory

This paper presents a new method to measure the sinking rates of individual phytoplankton “particles” (cells, chains, colonies, and aggregates) in the laboratory. Conventional particle tracking and high resolution video imaging were used to measure particle sinking rates and particle size. The stabilizing force of a very mild linear salinity gradient (1 ppt over 15 cm) prevented the formation of convection currents in the laboratory settling chamber. Whereas bulk settling methods such as SETCOL provide a single value of sinking rate for a population, this method allows the measurement of sinking rate and particle size for a large number of individual particles or phytoplankton within a population. The method has applications where sinking rates vary within a population, or where sinking rate-size relationships are important. Preliminary data from experiments with both laboratory and field samples of marine phytoplankton are presented here to illustrate the use of the technique, its applications, and limitations. Whereas this paper deals only with sinking phytoplankton, the method is equally valid for positively buoyant species, as well as nonbiological particles.

Dynamics of on-line gradient descent learning for multilayer neural networks

We consider the problem of on-line gradient descent learning for general two-layer neural networks. An analytic solution is presented and used to investigate the role of the learning rate in controlling the evolution and convergence of the learning process.

Computationally efficient natural gradient descent

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Modeling of a magneto-rheological (MR) fluid damper using a self tuning fuzzy mechanism

A magneto-rheological (MR) fluid damper is a semi-active control device that has recently begun to receive more attention in the vibration control community. However, the inherent nonlinear nature of the MR fluid damper makes it challenging to use this device to achieve high damping control system performance. Therefore the development of an accurate modeling method for a MR fluid damper is necessary to take advantage of its unique characteristics. Our goal was to develop an alternative method for modeling a MR fluid damper by using a self tuning fuzzy (STF) method based on neural technique. The behavior of the researched damper is directly estimated through a fuzzy mapping system. In order to improve the accuracy of the STF model, a back propagation and a gradient descent method are used to train online the fuzzy parameters to minimize the model error function. A series of simulations had been done to validate the effectiveness of the suggested modeling method when compared with the data measured from experiments on a test rig with a researched MR fluid damper. Finally, modeling results show that the proposed STF interference system trained online by using neural technique could describe well the behavior of the MR fluid damper without need of calculation time for generating the model parameters.

Utilizing voting systems for ranking user tweets

Twitter is a very popular social network website that allows users to publish short posts called tweets. Users in Twitter can follow other users, called followees. A user can see the posts of his followees on his Twitter profile home page. An information overload problem arose, with the increase of the number of followees, related to the number of tweets available in the user page. Twitter, similar to other social network websites, attempts to elevate the tweets the user is expected to be interested in to increase overall user engagement. However, Twitter still uses the chronological order to rank the tweets. The tweets ranking problem was addressed in many current researches. A sub-problem of this problem is to rank the tweets for a single followee. In this paper we represent the tweets using several features and then we propose to use a weighted version of the famous voting system Borda-Count (BC) to combine several ranked lists into one. A gradient descent method and collaborative filtering method are employed to learn the optimal weights. We also employ the Baldwin voting system for blending features (or predictors). Finally we use the greedy feature selection algorithm to select the best combination of features to ensure the best results.