The inter-relationships of managers' work time and personal time

School of Managemen

Purification and Characterization of OTF-l, A Transcription Factor Regulating Cell Cycle Expression of a Human Histone H2b Gene: Demonstration of its Functional Identity with NF-III, a Factor Required for Efficient Initiation of Adenovirus DNA Replication

An octamer-binding transcription factor, OTF-l, which stimulates transcription of a human histone H2b gene, has been purified from HeLa nuclear extracts. This purification was achieved through the use of DNA affinity chromatography, and the factor was unambiguously identified by renaturation of activity following SDS-polyacrylamide gel electrophoresis. The purified factor retained the ability to efficiently stimulate H2b transcription in a reconstituted in vitro system. This effect was dependent on an intact octamer element and was observed in the absence of other H2b promoter elements (except the TATA motif). This activity is absent from nuclear extracts prepared from cells synchronized in G2. However, the apparent mass and binding activity of the factor are unchanged in Sand G2. Because this factor can stimulate transcription in a G2 extract, we suggest that the modulation of activity is due to either in vivo constraints on binding or covalent (or other) modification(s). We have demonstrated that this factor is identical, by a number of criteria, to NF-llI. Therefore, OTF-l is able to stimulate the initiation of replication of adenovirus DNA. This effect was shown to be dependent on the presence of an intact NF-llI binding site in the adenovirus origin of replication. Finally, preliminary data suggesting that we have isolated a cDNA clone for this factor are presented and discussed

Systemic inflammation predicts all-cause mortality: a Glasgow Inflammation Outcome Study

Introduction: Markers of the systemic inflammatory response, including C-reactive protein and albumin (combined to form the modified Glasgow Prognostic Score), as well as neutrophil, lymphocyte and platelet counts have been shown to be prognostic of survival in patients with cancer. The aim of the present study was to examine the prognostic relationship between these markers of the systemic inflammatory response and all-cause, cancer, cardiovascular and cerebrovascular mortality in a large incidentally sampled cohort.<p></p> Methods: Patients (n = 160 481) who had an incidental blood sample taken between 2000 and 2008 were studied for the prognostic value of C-reactive protein (>10mg/l, albumin (>35mg/l), neutrophil (>7.5×109/l) lymphocyte and platelet counts. Also, patients (n = 52 091) sampled following the introduction of high sensitivity C-reactive protein (>3mg/l) measurements were studied. A combination of these markers, to make cumulative inflammation-based scores, were investigated.<p></p> Results: In all patients (n = 160 481) C-reactive protein (>10mg/l) (HR 2.71, p<0.001), albumin (>35mg/l) (HR 3.68, p<0.001) and neutrophil counts (HR 2.18, p<0.001) were independently predictive of all-cause mortality. These associations were also observed in cancer, cardiovascular and cerebrovascular mortality before and after the introduction of high sensitivity C-reactive protein measurements (>3mg/l) (n = 52 091). A combination of high sensitivity C-reactive protein (>3mg/l), albumin and neutrophil count predicted all-cause (HR 7.37, p<0.001, AUC 0.723), cancer (HR 9.32, p<0.001, AUC 0.731), cardiovascular (HR 4.03, p<0.001, AUC 0.650) and cerebrovascular (HR 3.10, p<0.001, AUC 0.623) mortality. Conclusion The results of the present study showed that an inflammation-based prognostic score, combining high sensitivity C-reactive protein, albumin and neutrophil count is prognostic of all-cause mortality

Expression of Blood Group Antigens by Cultured Human Epidermal Cells

The presence of blood group antigens on the surface of cultured human epidermal cells has been demonstrated using monoclonal antibody supernatants in indirect immunoperoxidase and immunofluorescence tests. An isoantigen pattern, consistent with the blood group of the donor infant, was detected in cultures derived from 10 different foreskin specimens, and in sections of the epidermis of 5 of these specimens. The A, B, and H antigens were found on the surface of cultured keratinocytes which resembled those of the spinous and granular cell layers of the in vivo epidermis. These antigens were readily detectable throughout the majority of the lifespan of the cells in vitro. This finding may be of relevance to those contemplating allograft transplantation of cultured human epidermis

Isolation of a Collagenase cDNA Clone and Measurement of Changing Collagenase mRNA Levels during Induction in Rabbit Synovial Fibroblasts.

To facilitate our studies on the mechanisms controlling collagenase production at a molecular level in rabbit synovial fibroblasts, we have constructed a cDNA library using mRNAs isolated from cells induced with crystals of monosodium urate monohydrate. We have screened this library with cDNA probes made from induced and control mRNA populations. From among 30 clones that hybridized preferentially to the induced-cell probe, 4 contained collagenase sequences. The largest, a clone of 650 base pairs, was identified by its ability to hybrid select a mRNA that could be translated in a cell-free system into a product that was precipitable with monospecific antibody to collagenase. Using this clone to probe blots of RNA from induced cells, we detected the appearance of a collagenase mRNA of 2.7 kilobases within 5 hr of addition of urate. The level of collagenase mRNA continued to increase for 35-40 hr, when it was 60 to 90 times more abundant in induced cells than in control cells. The increase in mRNA levels correlated with an increase in immunoreactive collagenase protein that was detectable in culture medium by 10 hr

To Trust or Not to Trust? Developing Trusted Digital Spaces through Timely Reliable and Personalized Provenance

Organizations are increasingly dependent on data stored and processed by distributed, heterogeneous services to make critical, high-value decisions. However, these service-oriented computing environments are dynamic in nature and are becoming ever more complex systems of systems. In such evolving and dynamic eco-system infrastructures, knowing how data was derived is of significant importance in determining its validity and reliability. To address this, a number of advocates and theorists postulate that provenance is critical to building trust in data and the services that generated it as it provides evidence for data consumers to judge the integrity of the results. This paper presents a summary of the STRAPP (trusted digital Spaces through Timely Reliable And Personalised Provenance) project, which is designing and engineering mechanisms to achieve a holistic solution to a number of real-world service-based decision-support systems

Minimum Information about a Neuroscience Investigation (MINI) Electrophysiology

This module represents the formalized opinion of the authors and the CARMEN consortium, which identifies the minimum information required to report the use of electrophysiology in a neuroscience study, for submission to the CARMEN system (www.carmen.org.uk).
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Pore structural evolution of shale following thermochemical treatment

Shales experience heat treatment concurrent with the presence of water or steam during reservoir engineering interventions, such as high pressure water fracking and in-situ combustion of hydrocarbons. This work utilises a novel technique, which is a combination of gas sorption overcondensation and integrated mercury porosimetry experiments, not used before for any type of porous material, to study the pore structure of a shale rock, and its evolution following thermal treatment in the presence of water. Overcondensation allows the extension of gas sorption beyond the limits of conventional experiments to enable direct study of macroporosity. Scanning curve experiments, initiated from the complete boundary desorption isotherm, that can only be obtained for macropores by overcondensation experiments, has revealed details of the relative pore size spatial disposition within the network. In particular, it has been found that the new large voids formed by treatment are shielded by relatively much narrower pore windows. Use of a range of different adsorbates, with differing polarity, has allowed the chemical nature of the pore surface before and after treatment to be probed. Integrated rate of gas sorption and mercury porosimetry experiments have determined the level of the particular contribution to mass transport rates of the newly introduced porosity generated by thermal treatment. Combined CXT and mercury porosimetry have allowed the mapping of the macroscopic spatial distribution of even the new mesoporosity, and revealed the degree of pervasiveness of the new voids that leads to a thousand-fold increase in mass transport on thermal treatment

Simon\u27s fundamental rich-get-richer model entails a dominant first-mover advantage

Herbert Simon\u27s classic rich-get-richer model is one of the simplest empirically supported mechanisms capable of generating heavy-tail size distributions for complex systems. Simon argued analytically that a population of flavored elements growing by either adding a novel element or randomly replicating an existing one would afford a distribution of group sizes with a power-law tail. Here, we show that, in fact, Simon\u27s model does not produce a simple power-law size distribution as the initial element has a dominant first-mover advantage, and will be overrepresented by a factor proportional to the inverse of the innovation probability. The first group\u27s size discrepancy cannot be explained away as a transient of the model, and may therefore be many orders of magnitude greater than expected. We demonstrate how Simon\u27s analysis was correct but incomplete, and expand our alternate analysis to quantify the variability of long term rankings for all groups. We find that the expected time for a first replication is infinite, and show how an incipient group must break the mechanism to improve their odds of success. We present an example of citation counts for a specific field that demonstrates a first-mover advantage consistent with our revised view of the rich-get-richer mechanism. Our findings call for a reexamination of preceding work invoking Simon\u27s model and provide an expanded understanding going forward

How do world and European standard populations impact burden of disease studies? A case study of disability-adjusted life years (DALYs) in Scotland

Background Disability-Adjusted Life Years (DALYs) are an established method for quantifying population health needs and guiding prioritisation decisions. Global Burden of Disease (GBD) estimates aim to ensure comparability between countries and over time by using age-standardised rates (ASR) to account for differences in the age structure of different populations. Different standard populations are used for this purpose but it is not widely appreciated that the choice of standard may affect not only the resulting rates but also the rankings of causes of DALYs. We aimed to evaluate the impact of the choice of standard, using the example of Scotland. Methods DALY estimates were derived from the 2016 Scottish Burden of Disease (SBoD) study for an abridged list of 68 causes of disease/injury, representing a three-year annual average across 2014–16. Crude DALY rates were calculated using Scottish national population estimates. DALY ASRs standardised using the GBD World Standard Population (GBD WSP) were compared to those using the 2013 European Standard Population (ESP2013). Differences in ASR and in rank order within the cause list were summarised for all-cause and for each individual cause. Results The ranking of causes by DALYs were similar using crude rates or ASR (ESP2013). All-cause DALY rates using ASR (GBD WSP) were around 26% lower. Overall 58 out of 68 causes had a lower ASR using GBD WSP compared with ESP2013, with the largest falls occurring for leading causes of mortality observed in older ages. Gains in ASR were much smaller in absolute scale and largely affected causes that operated early in life. These differences were associated with a substantial change to the ranking of causes when GBD WSP was used compared with ESP2013. Conclusion Disease rankings based on DALY ASRs are strongly influenced by the choice of standard population. While GBD WSP offers international comparability, within-country analyses based on DALY ASRs should reflect local age structures. For European countries, including Scotland, ESP2013 may better guide local priority setting by avoiding large disparities occurring between crude and age-standardised results sets, which could potentially confuse non-technical audiences