Estimating Density Dependence, Environmental Variance, and Long-Term Selection on a Stage-Structured Life History

A method for analyzing long-term demographic data on density-dependent stage-structured populations in a stochastic environment is derived to facilitate comparison of populations and species with different life histories. We assume that a weighted sum of stage abundances, N, exerts density dependence on stage-specific vital rates of survival and reproduction and that N has a small or moderate coefficient of variation. The dynamics of N are approximated as a univariate stochastic process governed by three key parameters: the density-independent growth rate, the net density dependence, and environmental variance in the life history. We show how to estimate the relative weighs of stages in N and the key parameters. Life history evolution represents a stochastic maximization of a simple function of the key parameters. The long-term selection gradient on the life history can be expressed as a vector of sensitivities of this function with respect to density-independent, density-dependent, and stochastic components of the vital rates. To illustrate the method, we analyze 38 years of demographic data on a great tit population, estimating the key parameters, which accurately predict the observed mean, coefficient of variation, and fluctuation rate of N; we also evaluate the long-term selection gradient on the life history.</p

Partial cooperative unfolding in proteins as observed by hydrogen exchange mass spectrometry

This is an Accepted Manuscript of an article published by Taylor & Francis in International Reviews in Physical Chemistry on 2013-1-1, available online: http://www.tandfonline.com/10.1080/0144235X.2012.751175.Many proteins do not exist in a single rigid conformation. Protein motions, or dynamics, exist and in many cases are important for protein function. The analysis of protein dynamics relies on biophysical techniques that can distinguish simultaneously existing populations of molecules and their rates of interconversion. Hydrogen exchange (HX) detected by mass spectrometry (MS) is contributing to our understanding of protein motions by revealing unfolding and dynamics on a wide timescale, ranging from seconds to hours to days. In this review we discuss HX MS-based analyses of protein dynamics, using our studies of multi-domain kinases as examples. Using HX MS, we have successfully probed protein dynamics and unfolding in the isolated SH3, SH2 and kinase domains of the c-Src and Abl kinase families, as well as the role of inter- and intra-molecular interactions in the global control of kinase function. Coupled with high-resolution structural information, HX MS has proved to be a powerful and versatile tool for the analysis of the conformational dynamics in these kinase systems, and has provided fresh insight regarding the regulatory control of these important signaling proteins. HX MS studies of dynamics are applicable not only to the proteins we illustrate here, but to a very wide range of proteins and protein systems, and should play a role in both classification of and greater understanding of the prevalence of protein motion

Consequences of digital mammography in population-based breast cancer screening: initial changes and long-term impact on referral rates

Contains fulltext : 89208.pdf (publisher's version ) (Closed access)OBJECTIVES: To investigate the referral pattern after the transition to full-field digital mammography (FFDM) in a population-based breast cancer screening programme. METHODS: Preceding the nationwide digitalisation of the Dutch screening programme, an FFDM feasibility study was conducted. Detection and referral rates for FFDM and screen-film mammography (SFM) were compared for first and subsequent screens. Furthermore, radiological characteristics of referrals in digital screening were assessed. RESULTS: A total of 312,414 screening mammograms were performed (43,913 digital and 268,501 conventional), with 4,473 consecutive referrals (966 following FFDM). Initially the FFDM referral rate peaked, and many false-positive results were noted as a consequence of pseudolesions and increased detection of (benign) microcalcifications. A higher overall referral rate was observed in FFDM screening in both first and subsequent examinations (p < .001), with a significant increase in cancer detection (p = .010). CONCLUSION: As a result of initial inexperience with digital screening images implementing FFDM in a population-based breast cancer screening programme may lead to a strong, but temporary increase in referral. Dedicated training in digital screening for radiographers and screening radiologists is therefore recommended. Referral rates decrease and stabilise (learning curve effect) at a higher level than in conventional screening, yet with significantly enhanced cancer detection.1 september 201

Modelling radiation-induced cell cycle delays

Ionizing radiation is known to delay the cell cycle progression. In particular after particle exposure significant delays have been observed and it has been shown that the extent of delay affects the expression of damage such as chromosome aberrations. Thus, to predict how cells respond to ionizing radiation and to derive reliable estimates of radiation risks, information about radiation-induced cell cycle perturbations is required. In the present study we describe and apply a method for retrieval of information about the time-course of all cell cycle phases from experimental data on the mitotic index only. We study the progression of mammalian cells through the cell cycle after exposure. The analysis reveals a prolonged block of damaged cells in the G2 phase. Furthermore, by performing an error analysis on simulated data valuable information for the design of experimental studies has been obtained. The analysis showed that the number of cells analyzed in an experimental sample should be at least 100 to obtain a relative error less than 20%.Comment: 19 pages, 11 figures, accepted for publication in Radiation and Environmental Biophysic

Создание развитых интернет-программ на примере построения виджет-программ

Рассмотрено применение методологии создания развитых Интернет-программ на основе Adobe Flex 2.0 с применением паттернов проектирования и архитектурного каркаса. Подход проиллюстрирован построением виджет-программ

Government debt expansion and stock returns

Using an international dataset, this paper documents a negative association between increases in the central government debt-to-GDP ratio and dollar-denominated stock index returns. Depending on the estimation method, raising the debt ratio by one percentage point diminishes the stock returns by between 39 to 95 basis points. We show that this result cannot be explained by changes in the investment risk. Instead, government debt issuance exerts upward pressure on private interest rates and appears to signal a greater tax burden in the future. These two factors coincide to produce a fall in stock market prices

Impact of carprofen administration on stress and nociception responses of calves to cautery dehorning

Citation: Stock, M. L., Barth, L. A., Van Engen, N. K., Millman, S. T., Gehring, R., Wang, C., . . . Coetzee, J. F. (2016). Impact of carprofen administration on stress and nociception responses of calves to cautery dehorning. Journal of Animal Science, 94(2), 542-555. doi:10.2527/jas2015-9510The objective of this study was to investigate the effects of carprofen administered immediately before cautery dehorning on nociception and stress. Forty Holstein calves aged approximately 6 to 8 wk old were either placebo treated and sham dehorned (n = 10) or cautery dehorned following administration of carprofen (1.4 mg/kg) subcutaneously (n = 10) or orally (n = 10) or a subcutaneous and oral placebo (n = 10) in a randomized, controlled trial. All animals were given a cornual nerve block using lidocaine before dehorning. Response variables including mechanical nociception threshold, ocular temperature, heart rate, and respiratory rate were measured before and following cautery dehorning for 96 h. Blood samples were also collected over 96 h following dehorning and analyzed for plasma cortisol and substance P concentrations by RIA. Plasma carprofen concentration and ex vivo PGE2 concentrations were also determined for this time period. Average daily gain was calculated for 7 d after dehorning. Data were analyzed using a linear mixed effects model with repeated measures, controlling for baseline values by their inclusion as a covariate in addition to planned contrasts. Dehorning was associated with decreased nociception thresholds throughout the study and a stress response immediately after dehorning, following the loss of local anesthesia, and 48 h after dehorning compared with sham-dehorned calves. Carprofen was well absorbed after administration and reached concentrations that inhibited ex vivo PGE2 concentrations for 72 h (subcutaneous) and 96 h (oral) compared with placebo-treated calves (P < 0.05). Carprofen-treated calves tended to be less sensitive (P = 0.097) to nociceptive threshold tests. Overall, at the dosing regimen studied, the effect of carprofen on sensitivity and stress following cautery dehorning was minimal. Consideration of route of administration and dose determination studies may be warranted