Modulation of CD14 and TLR4⋅MD‐2 Activities by a Synthetic Lipid A Mimetic

Monosaccharide lipid A mimetics based on a glucosamine core linked to two fatty acid chains and bearing one or two phosphate groups have been synthesized. Compounds 1 and 2 , each with one phosphate group, were practically inactive in inhibiting LPS‐induced TLR4 signaling and cytokine production in HEK‐blue cells and murine macrophages, but compound 3 , with two phosphate groups, was found to be active in efficiently inhibiting TLR4 signal in both cell types. The direct interaction between compound 3 and the MD‐2 coreceptor was investigated by NMR spectroscopy and molecular modeling/docking analysis. This compound also interacts directly with the CD14 receptor, stimulating its internalization by endocytosis. Experiments on macrophages show that the effect on CD14 reinforces the activity on MD‐2 ? TLR4 because compound 3 's activity is higher when CD14 is important for TLR4 signaling (i.e., at low LPS concentration). The dual targeting of MD‐2 and CD14, accompanied by good solubility in water and lack of toxicity, suggests the use of monosaccharide 3 as a lead compound for the development of drugs directed against TLR4related syndromes.     

DArTseq-Based High-Throughput SilicoDArT and SNP Markers Applied for Association Mapping of Genes Related to Maize Morphology

Today, agricultural productivity is essential to meet the needs of a growing population, and is also a key tool in coping with climate change. Innovative plant breeding technologies such as molecular markers, phenotyping, genotyping, the CRISPR/Cas method and next-generation sequencing can help agriculture meet the challenges of the 21st century more effectively. Therefore, the aim of the research was to identify single-nucleotide polymorphisms (SNPs) and SilicoDArT markers related to select morphological features determining the yield in maize. The plant material consisted of ninety-four inbred lines of maize of various origins. These lines were phenotyped under field conditions. A total of 14 morphological features was analyzed. The DArTseq method was chosen for genotyping because this technique reduces the complexity of the genome by restriction enzyme digestion. Subsequently, short fragment sequencing was used. The choice of a combination of restrictases allowed the isolation of highly informative low copy fragments of the genome. Thanks to this method, 90% of the obtained DArTseq markers are complementary to the unique sequences of the genome. All the observed features were normally distributed. Analysis of variance indicated that the main effect of lines was statistically significant (p < 0.001) for all 14 traits of study. Thanks to the DArTseq analysis with the use of next-generation sequencing (NGS) in the studied plant material, it was possible to identify 49,911 polymorphisms, of which 33,452 are SilicoDArT markers and the remaining 16,459 are SNP markers. Among those mentioned, two markers associated with four analyzed traits deserved special attention: SNP (4578734) and SilicoDArT (4778900). SNP marker 4578734 was associated with the following features: anthocyanin coloration of cob glumes, number of days from sowing to anthesis, number of days from sowing to silk emergence and anthocyanin coloration of internodes. SilicoDArT marker 4778900 was associated with the following features: number of days from sowing to anthesis, number of days from sowing to silk emergence, tassel: angle between the axis and lateral branches and plant height. Sequences with a length of 71 bp were used for physical mapping. The BLAST and EnsemblPlants databases were searched against the maize genome to identify the positions of both markers. Marker 4578734 was localized on chromosome 7, the closest gene was Zm00001d022467, approximately 55 Kb apart, encoding anthocyanidin 3-O-glucosyltransferase. Marker 4778900 was located on chromosome 7, at a distance of 45 Kb from the gene Zm00001d045261 encoding starch synthase I. The latter observation indicated that these flanking SilicoDArT and SNP markers were not in a state of linkage disequilibrium.     

Simultaneous identification of moving masses and structural damage

A method for simultaneous identification of moving masses and damages of the supporting structure from measured responses is presented. The interaction forces between the masses and the structure are used as excitation. Masses and damage extents are used as the optimization variables; compared to the approaches based on identification of the interaction forces, it allows ill-conditioning to be avoided and decreases the number of required sensors. The virtual distortion method is used; the damaged structure is modeled by the intact structure subjected to response-coupled virtual distortions and moving forces. These are related to the optimization variables via a linear system, which allows the optimization variables of both kinds to be treated in a unified way. A moving dynamic influence matrix is introduced to reduce the numerical costs. The adjoint variable method is used for fast sensitivity analysis. A numerical experiment of a three-span beam with 10% rms measurement error and three types of model errors is presented.     

Multi-objective decision support system in numerical reliability optimization of modern electronic packaging

Nowadays, numerical prototyping methods in electronic packaging are widely used. This is mainly due to cost and time reduction and improved functionality and reliability of final products. Recently, there has been a lot of interest and work conducted on advanced numerical optimization, which can be directly applied to prototyping. So far, the optimization is focused on one criteria while neglecting problem of multi-objectivity, which is not the best approach from practical point of view. Nevertheless, such an approach is jusitified from the point of view of complex analysis, interdisciplinary issues and reduced accuracy of numerical models. In reality, there are usually many criteria which, in order to solve the problem, have to be taken into consideration. There are many multi-objective methods, of which the Pareto set approach is mostly cited in the literature. The “problem” of multi-objective optimization is that not a single optimal solution has resulted but the set of equivalent optimal solutions. This set of equivalent optimal solutions is referenced as “the Pareto set”. From the mathematical point of view, every value from this set can be treated as optimal for certain assumed constraints. However, there could be some additional conditions which cannot be applied to optimization process and some of the results from the Pareto set are more likely (i.e., the fabrication process will be more repeatable) then the others. So, the question is: which value from the Pareto set should be taken to further processing? There are two possibilities: asking an expert for the advice or use the decision making system. Decision making methods based on multi-objective optimization could be referenced as “Multiple criteria decision making” (MCDM) or “Multiple criterial decision aid” (MCDA) systems. There are several groups of these methods: (a) mathematical multi-objective programming, (b) artificial intelligence methods, (c) simple arithmetic methods, and (d) advanced mathematical methods. The current paper will focus on designing and application of the decision support system for multi-objective numerical reliability optimization of electronic packaging. The work will be based on the self developed numerical tool based on Python Scrippting language and will present its application to selected microelectronic packages based on its numerical model elaborated in ABAQUS.     

Existence of perfect equilibria in a class of multigenerational stochastic games of capital accumulation

In this paper we introduce a model of multigenerational stochastic games of capital accumulation where each generation consists of m different players. The main objective is to prove the existence of a perfect stationary equilibrium in an infinite horizon game. A suitable change in the terminology used in this paper provides (in the case of perfect altruism between generations) a new Nash equilibrium theorem for standard stochastic games with uncountable state space.     

Online scheduling of bounded length jobs to maximize throughput

We consider an online scheduling problem, motivated by the issues present at the joints of networks using ATM and TCP/IP. Namely, IP packets have to be broken down into small ATM cells and sent out before their deadlines, but cells corresponding to different packets can be interwoven. More formally, we consider the online scheduling problem with preemptions, where each job j is revealed at release time r _j , and has processing time p _j , deadline?d _j , and weight w _j . A?preempted job can be resumed at any time. The goal is to maximize the total weight of all jobs completed on time. Our main results are as follows. Firstly, we prove that when the processing times of all jobs are at most k, the optimum deterministic competitive ratio is ??(k/log?k). Secondly, we give a deterministic algorithm with competitive ratio depending on the ratio between the smallest and the largest processing time of all jobs. In particular, it attains competitive ratio 5 in the case when all jobs have identical processing times, for which we give a lower bound of 2.598. The latter upper bound also yields an O(log?k)-competitive randomized algorithm for the variant with processing times bounded by k.     

NMR-Based Metabolomics in Investigation of the Radiation Induced Changes in Blood Serum of Head and Neck Cancer Patients and Its Correlation with the Tissue Volumes Exposed to the Particulate Doses

In the present study, we analyze the nuclear magnetic resonance (NMR) blood serum metabolic profiles of 106 head and neck squamous cell carcinoma (HNSCC) patients during radio (RT) and concurrent radio-chemotherapy (CHRT). Four different fractionation schemes were compared. The blood samples were collected weekly, from the day before the treatment until the last week of CHRT/RT. The NMR spectra were acquired on A Bruker 400 MHz spectrometer at 310 K and analyzed using multivariate methods. Seven metabolites were found significantly to be altered solely by radiotherapy: N-acetyl-glycoprotein (NAG), N-acetylcysteine, glycerol, glycolate and the lipids at 0.9, 1.3 and 3.2 ppm. The NMR results were correlated with the tissue volumes receiving a particular dose of radiation. The influence of the irradiated volume on the metabolic profile is weak and mainly limited to sparse correlations with the inflammatory markers, creatinine and the lymphocyte count in RT and the branched-chain amino-acids in CHRT. This is probably due to the optimal planning and delivery of radiotherapy improving sparing of the surrounding normal tissues and minimizing the differences between the patients (caused by the tumor location and size).     

Fluorescence Recognition of Anions Using a Heteroditopic Receptor: Homogenous and Two-Phase Sensing

In contrast to monotopic receptor 3, the anthracene functionalized squaramide dual-host receptor 1 is capable of selectively extracting sulfate salts, as was evidenced unambiguously by DOSY, mass spectrometry, fluorescent and ion chromatography measurements. The receptors were investigated in terms of anion and ion pair binding using the UV–vis and ¹H NMR titrations method in acetonitrile. The reference anion receptor 3, lacking a crown ether unit, was found to lose the enhancement in anion binding induced by the presence of cations. Besides the ability to bind anions in an enhanced manner exhibited by ion pair receptors 2 and 4, changing the 1-aminoanthracene substituent resulted in their exhibiting a lower anion affinity than receptor 1. By using receptor 1 and adjusting the water content in organic phase it was possible to selectively detect sulfates both by “turn-off” and “turn-on” fluorescence, and to do so homogenously and under interfacial conditions. Such properties of receptor 1 have allowed the development of a new type of sensor capable of recognizing and extracting potassium sulfate from the aqueous medium across a phase boundary, resulting in an appropriate fluorescent response in the organic solution.