A strategy for the characterization of minute chromosome rearrangements using multiple color fluorescence in situ hybridization with chromosome-specific DNA libraries and YAC clones

The identification of marker chromosomes in clinical and tumor cytogenetics by chromosome banding analysis can create problems. In this study, we present a strategy to define minute chromosomal rearrangements by multicolor fluorescence in situ hybridization (FISH) with whole chromosome painting probes derived from chromosome-specific DNA libraries and Alu-polymerase chain reaction (PCR) products of various region-specific yeast artificial chromosome (YAC) clones. To demonstrate the usefulness of this strategy for the characterization of chromosome rearrangements unidentifiable by banding techniques, an 8p+ marker chromosome with two extra bands present in the karyotype of a child with multiple anomalies, malformations, and severe mental retardation was investigated. A series of seven-color FISH experiments with sets of fluorochrome-labeled DNA library probes from flow-sorted chromosomes demonstrated that the additional segment on 8p+ was derived from chromosome 6. For a more detailed characterization of the marker chromosome, three-color FISH experiments with library probes specific to chromosomes 6 and 8 were performed in combination with newly established telomeric and subtelomeric YAC clones from 6q25, 6p23, and 8p23. These experiments demonstrated a trisomy 6pter6p22 and a monosomy 8pter8p23 in the patient. The present limitations for a broad application of this strategy and its possible improvements are discusse

The Relationship Between HR Practices and Firm Performance: Examining Causal Order

Significant research attention has been devoted to examining the relationship between HR practices and firm performance, and the research support has assumed HR as the causal variable. Using data from 45 business units (with 62 data points), this study examines how measures of HR practices correlate with past, concurrent, and future operational performance measures. The results indicate that correlations with performance measures at all three times are both high and invariant, and that controlling for past or concurrent performance virtually eliminates the correlation of HR with future performance. Implications are discussed

Electrochemical communication with the inside of cells using micro-patterned vertical carbon nanofibre electrodes

With the rapidly increasing demands for ultrasensitive biodetection, the design and applications of new nano-scale materials for development of sensors based on optical and electrochemical transducers have attracted substantial interest. In particular, given the comparable sizes of nanomaterials and biomolecules, there exist plenty of opportunities to develop functional nanoprobes with biomolecules for highly sensitive and selective biosensing, shedding new light on cellular behaviour. Towards this aim, herein we interface cells with patterned nano-arrays of carbon nanofibers forming a nanosensor-cell construct. We show that such a construct is capable of electrochemically communicating with the intracellular environment.This work was supported by the Leverhulme Trust [grant numbers F/00 094/BD, ECF/2013-603]; the Biotechnology and Biological Sciences Research Council [grant number BB/L017059/1]; the European Research Council [Consolidator Grant, number 614787], the Engineering and Physical Sciences Research Council [EP/K027263/1]; and the NC3Rs [grant number NC/L00058X/1]

The views of older women towards mammographic screening: a qualitative and quantitative study

Purpose: Mammographic screening has improved breast cancer survival in the screened age group. This improved survival has not been seen in older women (>70 years) where screening uptake is low. This study explores the views, knowledge and attitudes of older women towards screening. Methods: Women (>70) were interviewed about breast screening. Interview findings informed the development of a questionnaire which was sent to 1000 women (>70) to quantify their views regarding screening. Results: Twenty-six women were interviewed and a questionnaire designed. The questionnaire response rate was 48.3% (479/992). Over half (52.9%, 241/456) of respondents were unaware they could request mammography by voluntary self-referral and were unaware of how to arrange this. Most (81.5% 383/470) had not attended breast screening since turning 70. Most (75.6%, 343/454) felt screening was beneficial and would attend if invited. Most, (90.1%, 412/457) felt screening should be offered to all women regardless of age or health. Conclusions: There is a lack of knowledge about screening in older women. The majority felt that invitation to screening should be extended to the older age group regardless of age or health. The current under-utilised system of voluntary self referral is not supported by older women

Trypanocidal and leishmanicidal activity of six limonoids

Six limonoids [kotschyienone A and B (1, 2), 7-deacetylgedunin (3), 7-deacetyl-7-oxogedunin (4), andirobin (5) and methyl angolensate (6)] were investigated for their trypanocidal and leishmanicidal activities using bloodstream forms of Trypanosoma brucei and promastigotes of Leishmania major. Whereas all compounds showed anti-trypanosomal activity, only compounds 1–4 displayed anti-leishmanial activity. The 50% growth inhibition (GI 50) values for the trypanocidal and leishmanicidal activity of the compounds ranged between 2.5 and 14.9 μM. Kotschyienone A (1) was found to be the most active compound with a minimal inhibition concentration (MIC) value of 10 μM and GI 50 values between 2.5 and 2.9 μM. Only compounds 1 and 3 showed moderate cytotoxicity against HL-60 cells with MIC and GI 50 values of 100 μM and 31.5–46.2 μM, respectively. Compound 1 was also found to show activity against intracellular amastigotes of L. major with a GI 50 value of 1.5 μM. The results suggest that limonoids have potential as drug candidates for the development of new treatments against trypanosomiasis and leishmaniasis

Towards quantifying uncertainty in predictions of Amazon 'dieback'.

This is the final version of the article. It first appeared from The Royal Society via http://dx.doi.org/10.1098/rstb.2007.0028Simulations with the Hadley Centre general circulation model (HadCM3), including carbon cycle model and forced by a 'business-as-usual' emissions scenario, predict a rapid loss of Amazonian rainforest from the middle of this century onwards. The robustness of this projection to both uncertainty in physical climate drivers and the formulation of the land surface scheme is investigated. We analyse how the modelled vegetation cover in Amazonia responds to (i) uncertainty in the parameters specified in the atmosphere component of HadCM3 and their associated influence on predicted surface climate. We then enhance the land surface description and (ii) implement a multilayer canopy light interception model and compare with the simple 'big-leaf' approach used in the original simulations. Finally, (iii) we investigate the effect of changing the method of simulating vegetation dynamics from an area-based model (TRIFFID) to a more complex size- and age-structured approximation of an individual-based model (ecosystem demography). We find that the loss of Amazonian rainforest is robust across the climate uncertainty explored by perturbed physics simulations covering a wide range of global climate sensitivity. The introduction of the refined light interception model leads to an increase in simulated gross plant carbon uptake for the present day, but, with altered respiration, the net effect is a decrease in net primary productivity. However, this does not significantly affect the carbon loss from vegetation and soil as a consequence of future simulated depletion in soil moisture; the Amazon forest is still lost. The introduction of the more sophisticated dynamic vegetation model reduces but does not halt the rate of forest dieback. The potential for human-induced climate change to trigger the loss of Amazon rainforest appears robust within the context of the uncertainties explored in this paper. Some further uncertainties should be explored, particularly with respect to the representation of rooting depth

Parton Distributions for Event Generators

In this paper, conventional Global QCD analysis is generalized to produce parton distributions optimized for use with event generators at the LHC. This optimization is accomplished by combining the constraints due to existing hard-scattering experimental data with those from anticipated cross sections for key representative SM processes at LHC (by the best available theory) as joint input to the global analyses. The PDFs obtained in these new type of global analyses using matrix elements calculated in any given order will be best suited to work with event generators of that order, for predictions at the LHC. This is most useful for LO event generators at present. Results obtained from a few candidate PDF sets (labeled as CT09MCS, CT09MC1 and CT09MC2) for LO event generators produced in this way are compared with those from other approaches.Comment: 35 pages, 19 figures, and 4 table

Halfway to doubling of CO2 radiative forcing

The “double CO2” experiment has become a standard experiment in climate science, and a convenient way of comparing the sensitivity of different climate models. Double CO2 was first used by Arrhenius in the 19th century and in the classic paper by Manabe and Wetherald, published 50 years ago, which marked the start of the modern era of climate modeling. Doubling CO2 now has an iconic role in climate research. The equilibrium climate sensitivity (ECS) is defined as the global-mean surface temperature change resulting from a doubling of CO2, which is a headline result in Intergovernmental Panel on Climate Change (IPCC) assessments. In its most recent assessment IPCC concluded that the ECS “is likely in the range 1.5 to 4.5oC”. We show that we are now halfway to doubling of CO2 since pre-industrial times in terms of radiative forcing, but not in concentration

Early warning signals of simulated Amazon rainforest dieback

Copyright © The Author(s) 2013. This article is published with open access at Springerlink.comWe test proposed generic tipping point early warning signals in a complex climate model (HadCM3) which simulates future dieback of the Amazon rainforest. The equation governing tree cover in the model suggests that zero and non-zero stable states of tree cover co-exist, and a transcritical bifurcation is approached as productivity declines. Forest dieback is a non-linear change in the non-zero tree cover state, as productivity declines, which should exhibit critical slowing down. We use an ensemble of versions of HadCM3 to test for the corresponding early warning signals. However, on approaching simulated Amazon dieback, expected early warning signals of critical slowing down are not seen in tree cover, vegetation carbon or net primary productivity. The lack of a convincing trend in autocorrelation appears to be a result of the system being forced rapidly and non-linearly. There is a robust rise in variance with time, but this can be explained by increases in inter-annual temperature and precipitation variability that force the forest. This failure of generic early warning indicators led us to seek more system-specific, observable indicators of changing forest stability in the model. The sensitivity of net ecosystem productivity to temperature anomalies (a negative correlation) generally increases as dieback approaches, which is attributable to a non-linear sensitivity of ecosystem respiration to temperature. As a result, the sensitivity of atmospheric CO2 anomalies to temperature anomalies (a positive correlation) increases as dieback approaches. This stability indicator has the benefit of being readily observable in the real world.NERCJoint DECC/Defra Met Office Hadley Centre Climate ProgrammeUniversity of Exete

Engaging with community researchers for exposure science: lessons learned from a pesticide biomonitoring study

A major challenge in biomonitoring studies with members of the general public is ensuring their continued involvement throughout the necessary length of the research. The paper presents evidence on the use of community researchers, recruited from local study areas, as a mechanism for ensuring effective recruitment and retention of farmer and resident participants for a pesticides biomonitoring study. The evidence presented suggests that community researchers' abilities to build and sustain trusting relationships with participants enhanced the rigour of the study as a result of their on-the-ground responsiveness and flexibility resulting in data collection beyond targets expected