Modification of Behavior of Elastin-like Polypeptides by Changing Molecular Architecture

Elastin-like polypeptides (ELP) are environmentally responsive polymers that exhibit phase separation in response to external stimuli such as temperature, pH, light, and ionic strength. It has been shown that the sequence of the pentapeptide, its length, and the solution concentration are very important in the transition of the molecules from soluble to insoluble, but there has not been any detailed study of the effect of molecular architecture on the behavior of ELPs.In this study we designed, synthesized and characterized ELPs with different architectures and chemical identities to probe the effect of molecular design on the microscopic and macroscopic behavior of ELP molecules and to compare them to the linear ELP molecules. These new architectures also helped us better understand the theory of folding and aggregation of ELPs. The design was based on constructing three-armed star molecules by tagging a trimer forming oligomerization domain to the ELP chains. ELPs were chosen to have different chemical identities by changing the pentapetide sequence. The molecules were synthesized by molecular biology techniques and characterized by different methods.Our results show that capping the three ELP chains forces the chains to fold into more extended rod-like constructs prior to aggregation. A mathematical model was developed to predict the behavior of ELP chains at the transition temperature and it was shown that there is a difference between N- and C- terminal capping ELPs seem to fold at lower temperatures when their N-termini are held together. It was also shown that the constructs with both their ends capped can be designed such that they fold into a stable unit at much lower temperatures than the linear constructs without necessarily aggregation at higher temperatures. The trimer constructs were also used to make micellar aggregates that were characterized by dynamic and static light scattering. It was shown that the size of the micelles can be controlled by adjusting salt concentration or by making mixtures

Non-stationary Delayed Combinatorial Semi-Bandit with Causally Related Rewards

Sequential decision-making under uncertainty is often associated with long feedback delays. Such delays degrade the performance of the learning agent in identifying a subset of arms with the optimal collective reward in the long run. This problem becomes significantly challenging in a non-stationary environment with structural dependencies amongst the reward distributions associated with the arms. Therefore, besides adapting to delays and environmental changes, learning the causal relations alleviates the adverse effects of feedback delay on the decision-making process. We formalize the described setting as a non-stationary and delayed combinatorial semi-bandit problem with causally related rewards. We model the causal relations by a directed graph in a stationary structural equation model. The agent maximizes the long-term average payoff, defined as a linear function of the base arms' rewards. We develop a policy that learns the structural dependencies from delayed feedback and utilizes that to optimize the decision-making while adapting to drifts. We prove a regret bound for the performance of the proposed algorithm. Besides, we evaluate our method via numerical analysis using synthetic and real-world datasets to detect the regions that contribute the most to the spread of Covid-19 in Italy.Comment: 33 pages, 9 figures. arXiv admin note: text overlap with arXiv:2212.1292

Semi-Supervised Multiple Disambiguation

Determining the true entity behind an ambiguousword is an NP-Hard problem known as Disambiguation. Previoussolutions often disambiguate a single ambiguous mention acrossmultiple documents. They assume each document contains onlya single ambiguous word and a rich set of unambiguous contextwords. However, nowadays we require fast disambiguation ofshort texts (like news feeds, reviews or Tweets) with few contextwords and multiple ambiguous words. In this research we focuson Multiple Disambiguation (MD) in contrast to Single Disambiguation(SD). Our solution is inspired by a recent algorithm developed for SD. The algorithm categorizes documents by first,transferring them into a graph and then, clustering the graphbased on its topological structure. We changed the graph-baseddocument-modeling of the algorithm, to account for MD. Also,we added a new parameter that controls the resolution of theclustering. Then, we used a supervised sampling approach formerging the clusters when appropriate. Our algorithm, comparedwith the original model, achieved 10% higher quality in termsof F1-Score using only 4% sampling from the dataset.QC 20160407</p

Linear Combinatorial Semi-Bandit with Causally Related Rewards

In a sequential decision-making problem, having a structural dependency amongst the reward distributions associated with the arms makes it challenging to identify a subset of alternatives that guarantees the optimal collective outcome. Thus, besides individual actions' reward, learning the causal relations is essential to improve the decision-making strategy. To solve the two-fold learning problem described above, we develop the 'combinatorial semi-bandit framework with causally related rewards', where we model the causal relations by a directed graph in a stationary structural equation model. The nodal observation in the graph signal comprises the corresponding base arm's instantaneous reward and an additional term resulting from the causal influences of other base arms' rewards. The objective is to maximize the long-term average payoff, which is a linear function of the base arms' rewards and depends strongly on the network topology. To achieve this objective, we propose a policy that determines the causal relations by learning the network's topology and simultaneously exploits this knowledge to optimize the decision-making process. We establish a sublinear regret bound for the proposed algorithm. Numerical experiments using synthetic and real-world datasets demonstrate the superior performance of our proposed method compared to several benchmarks

The role of nanoliposome bilayer composition containing soluble leishmania antigen on maturation and activation of dendritic cells

Objective(s): Dendritic cells (DCs) play a critical role in activation of T cell responses. Induction of type1 T helper (Th1) immune response is essential to generate protective immunity against cutaneous leishmaniasis. The intrinsic tendency of liposomes to have interaction with antigen-presenting cells is the main rationale to utilize liposomes as antigen carriers. In the present study, the effect of lipid phase transition temperature on DCs maturation and liposome uptake by murine bone marrow derived dendritic cells and human monocyte derived dendritic cells was investigated.Materials and Methods: Two cationic liposomal formulations consisting of DOTAP and DSPC/DOTAP were prepared and contained soluble leishmania antigen. Liposomes were incubated with immature or mature DCs derived from bone marrow (BMDCs) of C57BL/6 (which are resistant to cutaneous leishmaniasis), BALB/c mice (susceptible to cutaneous leishmaniasis) or DCs derived from human monocytes (MoDCs). The expression of DCs co-stimulatory markers and liposomal uptake were evaluated by flow cytometry method. Results: DCs which were encountered to liposomes consisting of DSPC showed significantly more expression of co-stimulatory molecules in cells from both human and C57BL/6 mice but not in cells from BALB/c mice. Conclusion: It is concluded that cationic liposomes consisting of DSPC are an effective adjuvant for antigen delivery in case of MoDCs and BMDCs from C57BL/6 mice. Moreover, DCs from different origins act differently in uptake of liposomes

Graph Algorithms for Large-Scale and Dynamic Natural Language Processing

In Natural Language Processing, researchers design and develop algorithms to enable machines to understand and analyze human language. These algorithms benefit multiple downstream applications including sentiment analysis, automatic translation, automatic question answering, and text summarization. Topic modeling is one such algorithm that solves the problem of categorizing documents into multiple groups with the goal of maximizing the intra-group document similarity. However, the manifestation of short texts like tweets, snippets, comments, and forum posts as the dominant source of text in our daily interactions and communications, as well as being the main medium for news reporting and dissemination, increases the complexity of the problem due to scalability, sparsity, and dynamicity. Scalability refers to the volume of the messages being generated, sparsity is related to the length of the messages, and dynamicity is associated with the ratio of changes in the content and topical structure of the messages (e.g., the emergence of new phrases). We improve the scalability and accuracy of Natural Language Processing algorithms from three perspectives, by leveraging on innovative graph modeling and graph partitioning algorithms, incremental dimensionality reduction techniques, and rich language modeling methods. We begin by presenting a solution for multiple disambiguation on short messages, as opposed to traditional single disambiguation. The solution proposes a simple graph representation model to present topical structures in the form of dense partitions in that graph and applies disambiguation by extracting those topical structures using an innovative distributed graph partitioning algorithm. Next, we develop a scalable topic modeling algorithm using a novel dense graph representation and an efficient graph partitioning algorithm. Then, we analyze the effect of temporal dimension to understand the dynamicity in online social networks and present a solution for geo-localization of users in Twitter using a hierarchical model that combines partitioning of the underlying social network graph with temporal categorization of the tweets. The results show the effect of temporal dynamicity on users’ spatial behavior. This result leads to design and development of a dynamic topic modeling solution, involving an online graph partitioning algorithm and a significantly stronger language modeling approach based on the skip-gram technique. The algorithm shows strong improvement on scalability and accuracy compared to the state-of-the-art models. Finally, we describe a dynamic graph-based representation learning algorithm that modifies the partitioning algorithm to develop a generalization of our previous work. A strong representation learning algorithm is proposed that can be used for extracting high quality distributed and continuous representations out of any sequential data with local and hierarchical structural properties similar to natural language text.QC 20191125</p

Graph Algorithms for Large-Scale and Dynamic Natural Language Processing

In Natural Language Processing, researchers design and develop algorithms to enable machines to understand and analyze human language. These algorithms benefit multiple downstream applications including sentiment analysis, automatic translation, automatic question answering, and text summarization. Topic modeling is one such algorithm that solves the problem of categorizing documents into multiple groups with the goal of maximizing the intra-group document similarity. However, the manifestation of short texts like tweets, snippets, comments, and forum posts as the dominant source of text in our daily interactions and communications, as well as being the main medium for news reporting and dissemination, increases the complexity of the problem due to scalability, sparsity, and dynamicity. Scalability refers to the volume of the messages being generated, sparsity is related to the length of the messages, and dynamicity is associated with the ratio of changes in the content and topical structure of the messages (e.g., the emergence of new phrases). We improve the scalability and accuracy of Natural Language Processing algorithms from three perspectives, by leveraging on innovative graph modeling and graph partitioning algorithms, incremental dimensionality reduction techniques, and rich language modeling methods. We begin by presenting a solution for multiple disambiguation on short messages, as opposed to traditional single disambiguation. The solution proposes a simple graph representation model to present topical structures in the form of dense partitions in that graph and applies disambiguation by extracting those topical structures using an innovative distributed graph partitioning algorithm. Next, we develop a scalable topic modeling algorithm using a novel dense graph representation and an efficient graph partitioning algorithm. Then, we analyze the effect of temporal dimension to understand the dynamicity in online social networks and present a solution for geo-localization of users in Twitter using a hierarchical model that combines partitioning of the underlying social network graph with temporal categorization of the tweets. The results show the effect of temporal dynamicity on users’ spatial behavior. This result leads to design and development of a dynamic topic modeling solution, involving an online graph partitioning algorithm and a significantly stronger language modeling approach based on the skip-gram technique. The algorithm shows strong improvement on scalability and accuracy compared to the state-of-the-art models. Finally, we describe a dynamic graph-based representation learning algorithm that modifies the partitioning algorithm to develop a generalization of our previous work. A strong representation learning algorithm is proposed that can be used for extracting high quality distributed and continuous representations out of any sequential data with local and hierarchical structural properties similar to natural language text.QC 20191125</p

Graph Algorithms for Large-Scale and Dynamic Natural Language Processing

In Natural Language Processing, researchers design and develop algorithms to enable machines to understand and analyze human language. These algorithms benefit multiple downstream applications including sentiment analysis, automatic translation, automatic question answering, and text summarization. Topic modeling is one such algorithm that solves the problem of categorizing documents into multiple groups with the goal of maximizing the intra-group document similarity. However, the manifestation of short texts like tweets, snippets, comments, and forum posts as the dominant source of text in our daily interactions and communications, as well as being the main medium for news reporting and dissemination, increases the complexity of the problem due to scalability, sparsity, and dynamicity. Scalability refers to the volume of the messages being generated, sparsity is related to the length of the messages, and dynamicity is associated with the ratio of changes in the content and topical structure of the messages (e.g., the emergence of new phrases). We improve the scalability and accuracy of Natural Language Processing algorithms from three perspectives, by leveraging on innovative graph modeling and graph partitioning algorithms, incremental dimensionality reduction techniques, and rich language modeling methods. We begin by presenting a solution for multiple disambiguation on short messages, as opposed to traditional single disambiguation. The solution proposes a simple graph representation model to present topical structures in the form of dense partitions in that graph and applies disambiguation by extracting those topical structures using an innovative distributed graph partitioning algorithm. Next, we develop a scalable topic modeling algorithm using a novel dense graph representation and an efficient graph partitioning algorithm. Then, we analyze the effect of temporal dimension to understand the dynamicity in online social networks and present a solution for geo-localization of users in Twitter using a hierarchical model that combines partitioning of the underlying social network graph with temporal categorization of the tweets. The results show the effect of temporal dynamicity on users’ spatial behavior. This result leads to design and development of a dynamic topic modeling solution, involving an online graph partitioning algorithm and a significantly stronger language modeling approach based on the skip-gram technique. The algorithm shows strong improvement on scalability and accuracy compared to the state-of-the-art models. Finally, we describe a dynamic graph-based representation learning algorithm that modifies the partitioning algorithm to develop a generalization of our previous work. A strong representation learning algorithm is proposed that can be used for extracting high quality distributed and continuous representations out of any sequential data with local and hierarchical structural properties similar to natural language text.QC 20191125</p

Bayesian Linear Bandits for Large-Scale Recommender Systems

Potentially, taking advantage of available side information boosts the performance of recommender systems; nevertheless, with the rise of big data, the side information has often several dimensions. Hence, it is imperative to develop decision-making algorithms that can cope with such a high-dimensional context in real-time. That is especially challenging when the decision-maker has a variety of items to recommend. In this paper, we build upon the linear contextual multi-armed bandit framework to address this problem. We develop a decision-making policy for a linear bandit problem with high-dimensional context vectors and several arms. Our policy employs Thompson sampling and feeds it with reduced context vectors, where the dimensionality reduction follows by random projection. Our proposed recommender system follows this policy to learn online the item preferences of users while keeping its runtime as low as possible. We prove a regret bound that scales as a factor of the reduced dimension instead of the original one. For numerical evaluation, we use our algorithm to build a recommender system and apply it to real-world datasets. The theoretical and numerical results demonstrate the effectiveness of our proposed algorithm compared to the state-of-the-art in terms of computational complexity and regret performance.Comment: 10 pages, 2 figure