Characterization of N-Acetylated Heme Undecapeptide and Some of Its Derivatives in Aqueous Media: Monomeric Model Systems for Hemoproteins

The heme undecapeptide of cytochrome c has been converted to a bis(N-acetylated) derivative by reaction with acetic anhydride. The structure of the product has been confirmed by liquid secondary-ion mass spectrometry. As anticipated, the N-acetylated molecule exhibits much less tendency to aggregate in aqueous solution than its heme undecapeptide precursor. Around neutral pH, one axial ligand on the heme iron is provided by the same histidine residue as in the native cytochrome. The other axial ligand can be varied by the addition of exogenous donor species to produce a range of hemoprotein model compounds exhibiting mixed axial ligation. Contrary to the findings of Othman et al. [Biochemistry 1994, 33, 15437-15448] concerning heme octapeptide, the N-acetylated undecapeptide showed no tendency to bind more than one exogenous ligand per heme. At concentrations approaching millimolar and in the absence of exogenous ligands, the N-acetylated molecule may either be monodispersed, exhibiting a characteristic high-spin (S = (5)/(2)) ferric heme electron paramagnetic resonance (EPR) signal, or exist in an EPR-silent and presumably aggregated form. Interestingly, the system displays a novel dependence on the buffer with regard to which of these two forms is present in a given sample. There is no evidence in any of the spectra for the existence of an intermediate-spin (S = (3)/(2)) ferric heme as suggested by Wang and Van Wart [J. Phys. Chem. 1989, 93, 7925-7931] to be present in aqueous solutions of N-acetylated heme octapeptide. Also, in contrast to another earlier report concerning the underivatized undecapeptide [Clore et al. Inorg. Chim. Acta 1981, 56, 143-148], the N-acetylated molecule showed no evidence of catalase activity. In fact, the heme chromophore was surprisingly unstable in the presence of hydrogen peroxide.     

Adaptive automated construction of hybrid heuristics for exam timetabling and graph colouring problems

In this paper, we present a random iterative graph based hyper-heuristic to produce a collection of heuristic sequences to construct solutions of different quality. These heuristic sequences can be seen as dynamic hybridisations of different graph colouring heuristics that construct solutions step by step. Based on these sequences, we statistically analyse the way in which graph colouring heuristics are automatically hybridised. This, to our knowledge, represents a new direction in hyper-heuristic research. It is observed that spending the search effort on hybridising Largest Weighted Degree with Saturation Degree at the early stage of solution construction tends to generate high quality solutions. Based on these observations, an iterative hybrid approach is developed to adaptively hybridise these two graph colouring heuristics at different stages of solution construction. The overall aim here is to automate the heuristic design process, which draws upon an emerging research theme on developing computer methods to design and adapt heuristics automatically. Experimental results on benchmark exam timetabling and graph colouring problems demonstrate the effectiveness and generality of this adaptive hybrid approach compared with previous methods on automatically generating and adapting heuristics. Indeed, we also show that the approach is competitive with the state of the art human produced methods.     

Integral resource capacity planning for inpatient care services based on bed census predictions by hour

The design and operations of inpatient care facilities are typically largely historically shaped. A better match with the changing environment is often possible, and even inevitable due to the pressure on hospital budgets. Effectively organizing inpatient care requires simultaneous consideration of several interrelated planning issues. Also, coordination with upstream departments like the operating theatre and the emergency department is much-needed. We present a generic analytical approach to predict bed census on nursing wards by hour, as a function of the Master Surgical Schedule and arrival patterns of emergency patients. Along these predictions, insight is gained on the impact of strategic (ie, case mix, care unit size, care unit partitioning), tactical (ie, allocation of operating room time, misplacement rules), and operational decisions (ie, time of admission/discharge). The method is used in the Academic Medical Center Amsterdam as a decision-support tool in a complete redesign of the inpatient care operations.     

The practice and theory of automated timetabling (2016)

Annals of Operations Research -     

A new model for automated examination timetabling

Automated examination timetabling has been addressed by a wide variety of methodologies and techniques over the last ten years or so. Many of the methods in this broad range of approaches have been evaluated on a collection of benchmark instances provided at the University of Toronto in 1996. Whilst the existence of these datasets has provided an invaluable resource for research into examination timetabling, the instances have significant limitations in terms of their relevance to real-world examination timetabling in modern universities. This paper presents a detailed model which draws upon experiences of implementing examination timetabling systems in universities in Europe, Australasia and America.     

Spacetime code: Preliminaries and motivations

A review of the work of David Finkelstein and others on quantum topology is given, the intention being to present physical ideas and a progress report, which will help readers with the more detailed papers. Some new approaches involving walks on graphs are presented.