An ensemble evolutionary constraint-based approach to understand the emergence of metabolic phenotypes

Constraint-based modeling is largely used in computational studies of metabolism. We propose here a novel approach that aims to identify ensembles of flux distributions that comply with one or more target phenotype(s). The methodology has been tested on a small-scale model of yeast energy metabolism. The target phenotypes describe the differential pattern of ethanol production and O₂ consumption observed in “Crabtree-positive” and “Crabtree-negative” yeasts in changing environment (i.e., when the upper limit of glucose uptake is varied). The ensembles were obtained either by selection among sampled flux distributions or by means of a search heuristic (genetic algorithm). The former approach provided indication about the probability to observe a given phenotype, but the resulting ensembles could not be unambiguously partitioned into “Crabtree-positive” and “Crabtree-negative” clusters. On the contrary well-separated clusters were obtained with the latter method. The cluster analysis further allowed identification of distinct groups within each target phenotype. The method may thus prove useful in characterizing the design principles underlying metabolic plasticity arising from evolving physio-pathological or developmental constraints.     

A data collection protocol for real-time sensor applications

The nature of many sensor applications as well as continuously changing sensor data often imposes real-time requirements on wireless sensor network protocols. Due to numerous design constraints, such as limited bandwidth, memory and energy of sensor platforms, and packet collisions that can potentially lead to an unbounded number of retransmissions, timeliness techniques designed for real-time systems and real-time databases cannot be applied directly to wireless sensor networks. Our objective is to design a protocol for sensor applications that require periodic collection of raw data reports from the entire network in a timely manner. We formulate the problem as a graph coloring problem. We then present TIGRA (Timely Sensor Data Collection using Distributed Graph Coloring) — a distributed heuristic for graph coloring that takes into account application semantics and special characteristics of sensor networks. TIGRA ensures that no interference occurs and spatial channel reuse is maximized by assigning a specific time slot for each node. Although the end-to-end delay incurred by sensor data collection largely depends on a specific topology, platform, and application, TIGRA provides a transmission schedule that guarantees a deterministic delay on sensor data collection.     

An analysis of the transition proportion for binarization in handwritten historical documents

In this paper, we will present a mathematical analysis of the transition proportion for the normal threshold (NorT) based on the transition method. The transition proportion is a parameter of NorT which plays an important role in the theoretical development of NorT. We will study the mathematical forms of the quadratic equation from which NorT is computed. Through this analysis, we will describe how the transition proportion affects NorT. Then, we will prove that NorT is robust to inaccurate estimations of the transition proportion. Furthermore, our analysis extends to thresholding methods that rely on Bayes rule, and it also gives the mathematical bases for potential applications of the transition proportion as a feature to estimate stroke width and detect regions of interest. In the majority of our experiments, we used a database composed of small images that were extracted from DIBCO 2009 and H-DIBCO 2010 benchmarks. However, we also report evaluations using the original (H-)DIBCO?s benchmarks.     

Calcium: A comprehensive review on quantification,interaction with milk proteins and implications for processing of dairy products

Calcium (Ca) is a key micronutrient of high relevance for human nutrition that also influences the texture and taste of dairy products and their processability. In bovine milk, Ca is presented in several speciation forms, such as complexed with other milk components or free as ionic calcium while being distributed between colloidal and serum phases of milk. Partitioning of Ca between these phases is highly dynamic and influenced by factors, such as temperature, ionic strength, pH, and milk composition. Processing steps used during the manufacture of dairy products, such as preconditioning, concentration, acidification, salting, cooling, and heating, all contribute to modify Ca speciation and partition, thereby influencing product functionality, product yield, and fouling of equipment. This review aims to provide a comprehensive understanding of the influence of Ca partition on dairy products properties to support the development of kinetics models to reduce product losses and develop added-value products with improved functionality. To achieve this objective, approaches to separate milk phases, analytical approaches to determine Ca partition and speciation, the role of Ca on protein–protein interactions, and their influence on processing of dairy products are discussed.     

Invited review: Potential antiobesity effect of fermented dairy products

The growing prevalence of obesity affects millions of people around the world and has gained increased attention over the years because it is associated with the development of other chronic degenerative diseases. Different organizations recommend lifestyle changes to treat obesity; nevertheless, other strategies in addition to lifestyle changes have recently been suggested. One of these strategies is the use of probiotics in fermented dairy products; however, a need exists to review the different studies available related to the potential antiobesity effect of these products. Because probiotic fermented dairy products that support weight management are not available in the market, there is a great opportunity for the development of functional dairy products with new lactic acid bacteria that may present this added health benefit. Thus, the purpose of this overview is to highlight the importance of probiotic fermented dairy products as potential antiobesogenic functional foods and present in vitro and in vivo studies required before this kind of product may be introduced to the market. Overall, most studies attributed the antiobesity effect of fermented dairy foods to the probiotic strains present; however, bioactive peptides released during milk fermentation may also be responsible for this effect.     

Cell-Based Optimization of Covalent Reversible Ketoamide Inhibitors Bridging the Unprimed to the Primed Site of the Proteasome β5 Subunit

The ubiquitin-proteasome system (UPS) is an established therapeutic target for approved drugs to treat selected hematologic malignancies. While drug discovery targeting the UPS focuses on irreversibly binding epoxyketones and slowly-reversibly binding boronates, optimization of novel covalent-reversibly binding warheads remains largely unattended. We previously reported α-ketoamides to be a promising reversible lead motif, yet the cytotoxic activity required further optimization. This work focuses on the lead optimization of phenoxy-substituted α-ketoamides combining the structure-activity relationships from the primed and the non-primed site of the proteasome β5 subunit. Our optimization strategy is accompanied by molecular modeling, suggesting occupation of P1′ by a 3-phenoxy group to increase β5 inhibition and cytotoxic activity in leukemia cell lines. Key compounds were further profiled for time-dependent inhibition of cellular substrate conversion. Furthermore, the α-ketoamide lead structure 27 does not affect escape response behavior in Danio rerio embryos, in contrast to bortezomib, which suggests increased target specificity.     

Gender and posttraumatic stress: Sexual violence as an explanation for women's increased risk.

Women are approximately twice as likely as men to develop posttraumatic stress disorder (PTSD), but the cause of this disparity remains unclear. This study evaluated 2 alternative explanations of gender differences in PTSD, one pointing to an intrinsic vulnerability in women and the other emphasizing sexual violence across the life span. To test these competing theories, the authors analyzed National Violence Against Women Survey data from 591 victims of partner aggression. Results suggested that gender, when considered alone, has a small but significant effect on PTSD symptom severity. However, once models factor in sexual victimization history, the latter replaces gender as a key determinant of PTSD symptoms. These findings argue against theories of "feminine vulnerability," instead linking PTSD risk to sexually violent situations. (PsycINFO Database Record (c) 2010 APA, all rights reserved)