Ant Colony Optimization with Global Pheromone Evaluation for Scheduling a Single Machine

Ant Colony Optimization (ACO) is a metaheuristic that has recently been applied to scheduling problems. We propose an ACO algorithm for the Single Machine Total Weighted Tardiness Problem and compare it to an existing ACO algorithm for the unweighted problem. The proposed algorithm has some novel properties that are of general interest for ACO optimization. A main novelty is that the ants are guided on their way through the decision space by global pheromone information instead of using only local pheromone information. It is also shown that the ACO optimization behaviour can be improved when priority scheduling heuristics are adapted so that they appropriately reflect absolute quality differences between the alternatives before they are used by the ants. Further improvements can be obtained by identifying situations where the ants can perform optimal decisions.     

AN INVESTIGATION OF ANDREWS' PLOTS TO SHOW TIME VARIATION OF MODEL PARAMETERS

Abstract. Andrews (1972) introduced a method of plotting high-dimensional data in two dimensions. This method is exploited as a graphical technique for the examination of changes over time in the parameters of a time series model. Two sets of data are used to illustrate the method. Both polynomial and Fourier series models are used. Some statistical properties of the method are discussed.     

Pharmacophore‐Based Design of Novel Oxadiazoles as Selective Sphingosine‐1‐phosphate (S1P) Receptor Agonists with in vivo Efficacy

Sphingosine‐1‐phosphate (S1P) receptor agonists have shown promise as therapeutic agents for multiple sclerosis (MS) due to their regulatory roles within the immune, central nervous system, and cardiovascular system. Here, the design and optimization of novel [1,2,4]oxadiazole derivatives as selective S1P receptor agonists are described. The structure–activity relationship exploration was carried out on the three dominant segments of the series: modification of the polar head group (P), replacement of the oxadiazole linker (L) with different five‐membered heterocycles, and the use of diverse 2,2′‐disubstituted biphenyl moieties as the hydrophobic tail (H). All three segments have a significant impact on potency, S1P receptor subtype selectivity, physicochemical properties, and in vitro absorption, distribution, metabolism, excretion and toxicity (ADMET) profile of the compounds. From these optimization studies, a selective S1P₁ agonist, N‐methyl‐N‐(4‐{5‐[2‐methyl‐2′‐(trifluoromethyl)biphenyl‐4‐yl]‐1,2,4‐oxadiazol‐3‐yl}benzyl)glycine ( 45 ), and a dual S1P_1,5 agonist, N‐methyl‐N‐(3‐{5‐[2′‐methyl‐2‐(trifluoromethyl)biphenyl‐4‐yl]‐1,2,4‐oxadiazol‐3‐yl}benzyl)glycine ( 49 ), emerged as frontrunners. These compounds distribute predominantly in lymph nodes and brain over plasma and induce long lasting decreases in lymphocyte count after oral administration. When evaluated head‐to‐head in an experimental autoimmune encephalomyelitis mouse model, together with the marketed drug fingolimod, a pan‐S1P receptor agonist, S1P_1,5 agonist 49 demonstrated comparable efficacy while S1P₁‐selective agonist 45 was less potent. Compound 49 is not a prodrug, and its improved property profile should translate into a safer treatment of relapsing forms of MS.     

Recent advances in cured raw ham manufacture

Cured raw hams are a valuable and popular group of meat products. The consumption and international trade have increased during the last years, therefore new technologies to accelerate the production process and to increase product quality and safety are needed. In the current review, an overview of European protected cured raw hams is presented. Furthermore, traditional methods for cured raw ham production together with recent advantages in the techniques for pretreatment (trimming, blade tenderization, and freeze-thawing), curing/salting (tumbling, vacuum impregnation, pulsed pressure, ultrasound, pulsed electric fields, simultaneous thawing/salting), drying/ripening (Quick-Dry-Slice-process, oil drop application, high temperature short time process) and postprocessing (vacuum and modified atmosphere packaging, high hydrostatic pressure, high pressure carbon dioxide, high pressure carbon dioxide with ultrasound) are described. Moreover, application techniques and effects of protective cultures and starter cultures, such as molds, yeasts, coagulase-negative staphylococci and lactic acid bacteria, on cured raw ham quality and safety are reviewed.     

The Receptor AT1 Appears to Be Important for the Maintenance of Bone Mass and AT2 Receptor Function in Periodontal Bone Loss Appears to Be Regulated by AT1 Receptor

A large number of experimental studies has demonstrated that angiotensin II (Ang II) is involved in key events of the inflammatory process. This study aimed to evaluate the role of Ang II type 1 (AT1) and Ang II type 2 (AT2) receptors on periodontitis. Methods: Experimental periodontitis was induced by placing a 5.0 nylon thread ligature around the second upper left molar of AT1 mice, no-ligature or ligature (AT1-NL and AT1-L), AT2 (AT2-NL or AT2-L) and wild type (WT-NL or L). Alveolar bone loss was scanned using Micro-CT. Cytokines, peptides and enzymes were analyzed from gingival tissues by Elisa and RT-PCR. Results: The blockade of AT1 receptor resulted in bone loss, even in healthy animals. Ang II receptor blockades did not prevent linear bone loss. Ang II and Ang 1-7 levels were significantly increased in the AT2-L (p < 0.01) group compared to AT2-NL and AT1-L. The genic expression of the Mas receptor was significantly increased in WT-L and AT2-L compared to (WT-NL and AT2-NL, respectively) and in AT1-L. Conclusions: Our data suggest that the receptor AT1 appears to be important for the maintenance of bone mass. AT2 receptor molecular function in periodontitis appears to be regulated by AT1.     

Large-scale phenotypic analysis—the pilot project on yeast chromosome III

In 1993, a pilot project for the functional analysis of newly discovered open reading frames, presumably coding for proteins, from yeast chromosome III was launched by the European Community. In the frame of this programme, we have developed a large-scale screening for the identification of gene/protein functions via systematic phenotypic analysis. To this end, some 80 haploid mutant yeast strains were constructed, each carrying a targeted deletion of a single gene obtained by HIS3 or TRP1 transplacement in the W303 background and a panel of some 100 growth conditions was established, ranging from growth substrates, stress to, predominantly, specific inhibitors and drugs acting on various cellular processes. Furthermore, co-segregation of the targeted deletion and the observed phenotype(s) in meiotic products has been verified. The experimental procedure, using microtiter plates for phenotypic analysis of yeast mutants, can be applied on a large scale, either on solid or in liquid media. Since the minimal working unit of one 96-well microtiter plate allows the simultaneous analysis of at least 60 mutant strains, hundreds of strains can be handled in parallel. The high number of monotropic and pleiotropic phenotypes (62%) obtained, together with the acquired practical experience, have shown this approach to be simple, inexpensive and reproducible. It provides a useful tool for the yeast community for the systematic search of biochemical and physiological functions of unknown genes accounting for about a half of the 6000 genes of the complete yeast genome. © 1997 John Wiley & Sons, Ltd.