Synthesis and biological studies on analogs of cyclolinopeptide A with a shortened peptide chain

Continuing our work on the immunosuppressive activity of cyclolinopeptide A (CLA), a cyclic nonapeptide of the sequence: c-(-Leu-Ile-Ile-Leu-Val-Pro-Pro-Phe-Phe), we synthesized a series of 6 linear analogs of CLA, successively shortened at the N-terminus of the peptide chain. Immunosuppressive activity of acetates as well as trifluoroacetates of these peptides was investigated using PFC (humoral immunity) and DTH (cellular immunity) tests. It was found that the immunosuppressive potency of the peptides examined diminishes with shortening of the peptide chain. Octapeptide I with the sequence Ile-Ile-Leu-Val-Pro-Pro-Phe-Phe was found to be the most active of the whole series. The immunosuppressive activity increased again for a tripeptide fragment of CLA of the sequence Pro-Phe-Phe. The immunosuppressive activity of octapeptide probably depends on the suppression of IL-1, IL-6 and TNF production by the cells involved in immune and inflammatory response.     

Hypermobile Robots – the Survey

This article presents a survey on hypermobile robots – a group of articulated mobile robots that typically comprise of several segments with powered wheels, tracks, or legs to propel the vehicle forward. Segments are connected by 2- or 3-degree-of-freedom (DOF) joints that may or may not be powered and provide better mobility as compared with regular mobile robots. The origins are analyzed and over 14 projects are compared in order to find the best methodology of designing and developing hypermobile robots.     

An approach to reduce energy consumption and performance losses on heterogeneous servers using power capping

Journal of Scheduling - Rapid growth of demand for remote computational power, along with high energy costs and infrastructure limits, has led to treating power usage as a primary constraint in...     

Modelling and solving grid resource allocation problem with network resources for workflow applications

A problem of allocating resources of a grid to workflow applications is considered. The problem consists, generally, in allocating distributed grid resources to tasks of a workflow in such a way that the resource demands of each task are satisfied. Grid resources are divided into computational resources and network resources. Computational tasks and transmission tasks of a workflow are distinguished. We present a model of the problem, and an algorithm for finding feasible resource allocations. A numerical example is included, showing the importance of the resource allocation phase on a grid. Some conclusions and directions for future research are given.     

Speeding up global optimization with the help of intelligent supervisors

It is shown in the paper that Developmental Genetic Programming is an efficient tool for evolutionary development of intelligent supervisors that solve an extension of Resource-Constrained Project Scheduling Problem. The extension assumes that resources are only partially available. It also assumes that renewable resources affect the project cost. The cost should be as low as possible and a deadline of the project must be met. This is apparent with regard to software houses and building enterprises. Computational experiments showed that supervisors find solutions of the problem much faster than other genetic approaches. A specific property of the supervisor is that it has various strategies of allocating the resources to the tasks. The supervisor uses the strategies in order to develop a procedure for producing the best schedule for the whole project. The analysis of the evolutionary process was performed and experimental results were compared with the optimal ones obtained by means of the exhaustive search method.     

3D‐vision based detection,localization, and sizing of broccoli heads in the field

This paper describes a 3D vision system for robotic harvesting of broccoli using low‐cost RGB‐D sensors, which was developed and evaluated using sensory data collected under real‐world field conditions in both the UK and Spain. The presented method addresses the tasks of detecting mature broccoli heads in the field and providing their 3D locations relative to the vehicle. The paper evaluates different 3D features, machine learning, and temporal filtering methods for detection of broccoli heads. Our experiments show that a combination of Viewpoint Feature Histograms, Support Vector Machine classifier, and a temporal filter to track the detected heads results in a system that detects broccoli heads with high precision. We also show that the temporal filtering can be used to generate a 3D map of the broccoli head positions in the field. Additionally, we present methods for automatically estimating the size of the broccoli heads, to determine when a head is ready for harvest. All of the methods were evaluated using ground‐truth data from both the UK and Spain, which we also make available to the research community for subsequent algorithm development and result comparison. Cross‐validation of the system trained on the UK dataset on the Spanish dataset, and vice versa, indicated good generalization capabilities of the system, confirming the strong potential of low‐cost 3D imaging for commercial broccoli harvesting.     

Novel Cyclopentaquinoline and Acridine Analogs as Multifunctional,Potent Drug Candidates in Alzheimer’s Disease

A series of new cyclopentaquinoline derivatives with 9-acridinecarboxylic acid and a different alkyl chain length were synthesized, and their ability to inhibit cholinesterases was evaluated. All designed compounds, except derivative 3f, exhibited a selectivity for butyrylcholinesterase (BuChE) with IC₅₀ values ranging from 103 to 539 nM. The 3b derivative revealed the highest inhibitory activity towards BuChE (IC₅₀ = 103.73 nM) and a suitable activity against AChE (IC₅₀ = 272.33 nM). The 3f derivative was the most active compound to AChE (IC₅₀ = 113.34 nM) with satisfactory activity towards BuChE (IC₅₀ = 203.52 nM). The potential hepatotoxic effect was evaluated for both 3b and 3f compounds. The 3b and 3f potential antioxidant activity was measured using the ORAC-FL method. The 3b and 3f derivatives revealed a significantly higher antioxidant potency, respectively 35 and 25 higher than tacrine. Theoretical, physicochemical, and pharmacokinetic properties were calculated using ACD Labs Percepta software. Molecular modeling and kinetic study were used to reveal the mechanism of cholinesterase inhibition in the most potent compounds: 3b and 3f.     

Albumin Binds Doxorubicin via Self–Assembling Dyes as Specific Polymolecular Ligands

Congo red (CR) type self–assembled ribbon–like structures (SRLS) were previously shown to interact with some proteins, including albumin. SRLS also complex with some drugs with a flat, ring–shaped structure with aromatic characteristics, intercalating them into their ribbon structure. The combination of interaction with proteins and drug binding by SRLS enables the use of such systems for immunotargeting. It is especially interesting in the case of chemotherapeutic agents. The present experiments aimed to show that the model carrier system composed of supramolecular albumin and Congo red efficiently binds doxorubicin (Dox) and that the drug can be released at reduced pH. The presented results come from the studies on such complexes differing in the molar ratio of CR to Dox. The following methods were used for the analysis: electrophoresis, dialysis, gel filtration, spectral analysis, and analysis of the size of the hydrodynamic radius using the dynamic light scattering method (DLS). The applied methods confirmed the formation of the CR–Dox complex, with large dimensions and changed properties compared with free CR. The presented results show that albumin binds both CR and its complex with Dox. Various CR–Dox molar ratios, 5:1, 2:1, and 1:1, were analyzed. The confirmation of the possibility of releasing the drug from the carriers thus formed was also obtained. The presented research is important due to the search for optimal solutions for the use of SRLS in drug immunotargeting, with particular emphasis on chemotherapeutic agents.