Workshop on the Early Earth: The Interval from Accretion to the Older Archean

Presentation abstracts are compiled which address various issues in Earth developmental processes in the first one hundred million years. The session topics included: accretion of the Earth (processes accompanying immediately following the accretion, including core formation); impact records and other information from planets and the Moon relevant to early Earth history; isotopic patterns of the oldest rocks; and igneous, sedimentary, and metamorphic petrology of the oldest rocks

On the quasi-steady state assumption applied to Michaelis-Menten and suicide substrate reactions with diffusion

We consider a recent extension to the validity of the quasi-steady-state assumption (QSSA) which includes the case where the ratio of the initial enzyme to substrate concentration is not necessarily small. We extend the analysis to include diffusion of substrate, in which case the initial enzyme to substrate ratio is spatially dependent and no longer constant. We show that the region in which the QSSA holds depends on the nature of the enzyme-substrate reaction: if the enzyme is inactivated by the substrate then the QSSA holds in a growing disc; if the enzyme is unchanged after reaction then the QSSA holds in a ring travelling through space

Suicide substrate reaction-diffusion equations: varying the source

The suicide substrate reaction is a model for certain enzyme-inhibiting drugs. This reaction system is examined assuming that the substrate diffuses freely while the enzyme remains fixed. Two sets of initial and boundary conditions are examined: one modelling an instantaneous point source, akin to an injection of substrate, the other, a continuous point source, akin to a continuing influx, or intravenous drip, of substrate. The quasi-steady-state assumption is applied to obtain analytical solutions for a limited parameter space. Finally, further applications of numerical and analytical experimentation on pharmaceutical mechanisms are described

On the kinetics of suicide substrates

We consider a realistic suicide substrate reaction which can be represented by four rate equations for the concentrations of the various molecules as functions of time. We present a general procedure to obtain accurate, approximate solutions analytically in terms of the rate equation parameters. This systematic technique provides more accurate approximations to the exact (numerical) solutions than other approximate methods which have been proposed based on a pseudo-steady state hypothesis

A guided search non-dominated sorting genetic algorithm for the multi-objective university course timetabling problem

Copyright @ Springer-Verlag Berlin Heidelberg 2011.The university course timetabling problem is a typical combinatorial optimization problem. This paper tackles the multi-objective university course timetabling problem (MOUCTP) and proposes a guided search non-dominated sorting genetic algorithm to solve the MOUCTP. The proposed algorithm integrates a guided search technique, which uses a memory to store useful information extracted from previous good solutions to guide the generation of new solutions, and two local search schemes to enhance its performance for the MOUCTP. The experimental results based on a set of test problems show that the proposed algorithm is efficient for solving the MOUCTP

Recent developments in CID imaging

Readout of CID imaging arrays was first performed by injecting and detecting the signal charge from each sensing site in sequence. A new readout method, termed parallel injection, has been developed in which the functions of signal charge detection and injection have been separated. The level of signal charge at each sensing site is detected during a line scan, and during the line retrace interval, all charge in the selected line is injected. The parallel injection technique is well adapted to TV scan formats in that the signal is read out at high speed, line by line. A 244 line by 248 element TV compatible imager, employing this technique and including an on chip preamplifier, has been constructed and operation demonstrated

A Component Based Heuristic Search Method with Evolutionary Eliminations

Nurse rostering is a complex scheduling problem that affects hospital personnel on a daily basis all over the world. This paper presents a new component-based approach with evolutionary eliminations, for a nurse scheduling problem arising at a major UK hospital. The main idea behind this technique is to decompose a schedule into its components (i.e. the allocated shift pattern of each nurse), and then to implement two evolutionary elimination strategies mimicking natural selection and natural mutation process on these components respectively to iteratively deliver better schedules. The worthiness of all components in the schedule has to be continuously demonstrated in order for them to remain there. This demonstration employs an evaluation function which evaluates how well each component contributes towards the final objective. Two elimination steps are then applied: the first elimination eliminates a number of components that are deemed not worthy to stay in the current schedule; the second elimination may also throw out, with a low level of probability, some worthy components. The eliminated components are replenished with new ones using a set of constructive heuristics using local optimality criteria. Computational results using 52 data instances demonstrate the applicability of the proposed approach in solving real-world problems.Comment: 27 pages, 4 figure

A Metabolic Dependency for Host Isoprenoids in the Obligate Intracellular Pathogen Rickettsia parkeri Underlies a Sensitivity to the Statin Class of Host-Targeted Therapeutics.

Gram-negative bacteria in the order Rickettsiales have an obligate intracellular growth requirement, and some species cause human diseases such as typhus and spotted fever. The bacteria have evolved a dependence on essential nutrients and metabolites from the host cell as a consequence of extensive genome reduction. However, it remains largely unknown which nutrients they acquire and whether their metabolic dependency can be exploited therapeutically. Here, we describe a genetic rewiring of bacterial isoprenoid biosynthetic pathways in the Rickettsiales that has resulted from reductive genome evolution. Furthermore, we investigated whether the spotted fever group Rickettsia species Rickettsia parkeri scavenges isoprenoid precursors directly from the host. Using targeted mass spectrometry, we found that infection caused decreases in host isoprenoid products and concomitant increases in bacterial isoprenoid metabolites. Additionally, we report that treatment of infected cells with statins, which inhibit host isoprenoid synthesis, prohibited bacterial growth. We show that growth inhibition correlates with changes in bacterial size and shape that mimic those caused by antibiotics that inhibit peptidoglycan biosynthesis, suggesting that statins lead to an inhibition of cell wall synthesis. Altogether, our results describe a potential Achilles' heel of obligate intracellular pathogens that can potentially be exploited with host-targeted therapeutics that interfere with metabolic pathways required for bacterial growth.IMPORTANCE Obligate intracellular pathogens, which include viruses as well as certain bacteria and eukaryotes, are a subset of infectious microbes that are metabolically dependent on and unable to grow outside an infected host cell because they have lost or lack essential biosynthetic pathways. In this study, we describe a metabolic dependency of the bacterial pathogen Rickettsia parkeri on host isoprenoid molecules that are used in the biosynthesis of downstream products, including cholesterol, steroid hormones, and heme. Bacteria make products from isoprenoids, such as an essential lipid carrier for making the bacterial cell wall. We show that bacterial metabolic dependency can represent a potential Achilles' heel and that inhibiting host isoprenoid biosynthesis with the FDA-approved statin class of drugs inhibits bacterial growth by interfering with the integrity of the cell wall. This work supports the potential to treat infections by obligate intracellular pathogens through inhibition of host biosynthetic pathways that are susceptible to parasitism

Tetanus infection in an HIV-positive patient with a history of prior tetanus vaccinations: Case report

An HIV-positive woman (previously vaccinated against tetanus) presented with tetanus infection after uvulectomy and manual vacuum aspiration (MVA).The course of her disease and treatment exposed critical issues in the proper prophylaxis and management of tetanus, particularly in a limited-resource setting with a high prevalence of both HIV and tetanus infections