Modeling Dual Pathways for the Metazoan Spindle Assembly Checkpoint

Using computational modelling, we investigate mechanisms of signal transduction focusing on the spindle assembly checkpoint where a single unattached kinetochore is able to signal to prevent cell cycle progression. This inhibitory signal switches off rapidly once spindle microtubules have attached to all kinetochores. This requirement tightly constrains the possible mechanisms. Here we investigate two possible mechanisms for spindle checkpoint operation in metazoan cells, both supported by recent experiments. The first involves the free diffusion and sequestration of cell-cycle regulators. This mechanism is severely constrained both by experimental fluorescence recovery data and also by the large volumes involved in open mitosis in metazoan cells. Using a simple mathematical analysis and computer simulation, we find that this mechanism can generate the inhibition found in experiment but likely requires a two stage signal amplification cascade. The second mechanism involves spatial gradients of a short-lived inhibitory signal that propagates first by diffusion but then primarily via active transport along spindle microtubules. We propose that both mechanisms may be operative in the metazoan spindle assembly checkpoint, with either able to trigger anaphase onset even without support from the other pathway.Comment: 9 pages, 2 figure

Scattering of rare-gas atoms at a metal surface: evidence of anticorrugation of the helium-atom potential-energy surface and the surface electron density

Recent measurements of the scattering of He and Ne atoms at Rh(110) suggest that these two rare-gas atoms measure a qualitatively different surface corrugation: While Ne atom scattering seemingly reflects the electron-density undulation of the substrate surface, the scattering potential of He atoms appears to be anticorrugated. An understanding of this perplexing result is lacking. In this paper we present density functional theory calculations of the interaction potentials of He and Ne with Rh(110). We find that, and explain why, the nature of the interaction of the two probe particles is qualitatively different, which implies that the topographies of their scattering potentials are indeed anticorrugated.Comment: RevTeX, 4 pages, 10 figure

Endstates in multichannel spinless p-wave superconducting wires

Multimode spinless p-wave superconducting wires with a width W much smaller than the superconducting coherence length \xi are known to have multiple low-energy subgap states localized near the wire's ends. Here we compare the typical energies of such endstates for various terminations of the wire: A superconducting wire coupled to a normal-metal stub, a weakly disordered superconductor wire and a wire with smooth confinement. Depending on the termination, we find that the energies of the subgap states can be higher or lower than for the case of a rectangular wire with hard-wall boundaries.Comment: 10 pages, 7 figure

Integrating tuberculosis and HIV care in the primary care setting in South Africa.

BACKGROUND: In many countries including South Africa, the increasing human immunodeficiency virus (HIV) and tuberculosis (TB) epidemics have impacted significantly on already weakened public health services. This paper reviews the scope, process and performance of the HIV and TB services in a primary care setting where antiretroviral therapy is provided, in Khayelitsha, South Africa, in order to assess whether there is a need for some form of integration. METHODS: The scope and process of both services were assessed through observations of the service and individual and group interviews with key persons. The performance was assessed by examining the 2001-2002 reports from the health information system and clinical data. RESULTS: The TB service is programme oriented to the attainment of an 85% cure rate amongst smear-positive patients while the HIV service has a more holistic approach to the patient with HIV. The TB service is part of a well-established programme that is highly standardized. The HIV service is in the pilot phase. There is a heavy load at both services and there is large degree of cross-referral between the two services. There are lessons that can be learnt from each service. There is an overlap of activities, duplication of services and under-utilization of staff. There are missed opportunities for TB and HIV prevention, diagnosis and management. CONCLUSIONS: The study suggests that there may be benefits to integrating HIV and TB services. Constraints to this process are discussed

MLS: Airplane system modeling

Analysis, modeling, and simulations were conducted as part of a multiyear investigation of the more important airplane-system-related items of the microwave landing system (MLS). Particular emphasis was placed upon the airplane RF system, including the antenna radiation distribution, the cabling options from the antenna to the receiver, and the overall impact of the airborne system gains and losses upon the direct-path signal structure. In addition, effort was expended toward determining the impact of the MLS upon the airplane flight management system and developing the initial stages of a fast-time MLS automatic control system simulation model. Results ot these studies are presented

Disorder induced local density of states oscillations on narrow Ag(111) terraces

The local density of states of Ag(111) has been probed in detail on disordered terraces of varying width by dI/dV-mapping with a scanning tunneling microscope at low temperatures. Apparent shifts of the bottom of the surface-state band edge from terrace induced confinement are observed. Disordered terraces show interesting contrast reversals in the dI/dV maps as a function of tip-sample voltage polarity with details that depend on the average width of the terrace and the particular edge profile. In contrast to perfect terraces with straight edges, standing wave patterns are observed parallel to the step edges, i.e. in the non-confined direction. Scattering calculations based on the Ag(111) surface states reproduce these spatial oscillations and all the qualitative features of the standing wave patterns, including the polarity-dependent contrast reversals.Comment: 19 pages, 12 figure

Human resource requirements for quality-assured electronic data capture of the tuberculosis case register

<p>Abstract</p> <p>Background</p> <p>The tuberculosis case register is the data source for the reports submitted by basic management units to the national tuberculosis program. Our objective was to measure the data entry time required to complete and double-enter one record, and to estimate the time for the correction of errors in the captured information from tuberculosis case registers in Cambodia and Viet Nam. This should assist in quantifying the additional requirements in human resources for national programs moving towards electronic recording and reporting.</p> <p>Methods</p> <p>Data from a representative sample of tuberculosis case registers from Cambodia and Viet Nam were double-entered and discordances resolved by rechecking the original case register. Computer-generated data entry time recorded the time elapsed between opening of a new record and saving it to disk.</p> <p>Results</p> <p>The dataset comprised 22,732 double-entered records of 11,366 patients (37.1% from Cambodia and 62.9% from Viet Nam). The mean data entry times per record were 97.5 (95% CI: 96.2-98.8) and 66.2 (95% CI: 59.5-73.0) seconds with medians of 90 and 31 s respectively in Cambodia and in Viet Nam. The percentage of records with an error was 6.0% and 39.0% respectively in Cambodia and Viet Nam. Data entry time was inversely associated with error frequency. We estimate that approximately 118-person-hours were required to produce 1,000 validated records.</p> <p>Conclusions</p> <p>This study quantifies differences between two countries for data entry time for the tuberculosis case register and frequencies of data entry errors and suggests that higher data entry speed is partially offset by requiring revisiting more records for corrections.</p

Site determination and thermally assisted tunneling in homogenous nucleation

A combined low-temperature scanning tunneling microscopy and density functional theory study on the binding and diffusion of copper monomers, dimers, and trimers adsorbed on Cu(111) is presented. Whereas atoms in trimers are found in fcc sites only, monomers as well as atoms in dimers can occupy the stable fcc as well as the metastable hcp site. In fact the dimer fcc-hcp configuration was found to be only 1.3 meV less favorable with respect to the fcc-fcc configuration. This enables a confined intra-cell dimer motion, which at temperatures below 5 K is dominated by thermally assisted tunneling.Comment: 4 pages, 4 figure

Infinitesimally Robust Estimation in General Smoothly Parametrized Models

We describe the shrinking neighborhood approach of Robust Statistics, which applies to general smoothly parametrized models, especially, exponential families. Equal generality is achieved by object oriented implementation of the optimally robust estimators. We evaluate the estimates on real datasets from literature by means of our R packages ROptEst and RobLox