Data journeys: Capturing the socio-material constitution of data objects and flows

In this paper, we discuss the development and piloting of a new methodology for illuminating the socio-material con- stitution of data objects and flows as data move between different sites of practice. The data journeys approach contributes to the development of critical, qualitative methodologies that can address the geographic and temporal scale of emerging knowledge infrastructures, and capture the ‘life of data’ from their initial generation through to re-use in different contexts. We discuss the theoretical development of the data journeys methodology and the application of the approach on a project examining meteorological data on their journey from initial production through to being re- used in climate science and financial markets. We then discuss three key conceptual findings from this project about: (1) the socio-material constitution of digital data objects, (2) ‘friction’ in the movement of data through space and time and (3) the mutability of digital data as a material property that contributes to driving the movement of data between different sites of practice

Crystal structure of a thermostable Bacillus DNA polymerase l large fragment at 2.1 Å resolution

AbstractBackground: The study of DNA polymerases in the Pol l family is central to the understanding of DNA replication and repair. DNA polymerases are used in many molecular biology techniques, including PCR, which require a thermostable polymerase. In order to learn about Pol l function and the basis of thermostability, we undertook structural studies of a new thermostable DNA polymerase.Results: A DNA polymerase large, Klenow-like, fragment from a recently identified thermostable strain of Bacillus stearothermophilus (BF) was cloned, sequenced, overexpressed and characterized. Its crystal structure was determined to 2.1 Å resolution by the method of multiple isomorphous replacement.Conclusions: This structure represents the highest resolution view of a Pol l enzyme obtained to date. Comparison of the three Pol l structures reveals no compelling evidence for many of the specific interactions that have been proposed to induce thermostability, but suggests that thermostability arises from innumerable small changes distributed throughout the protein structure. The polymerase domain is highly conserved in all three proteins. The N-terminal domains are highly divergent in sequence, but retain a common fold. When present, the 3′-5′ proofreading exonuclease activity is associated with this domain. Its absence is associated with changes in catalytic residues that coordinate the divalent ions required for activity and in loops connecting homologous secondary structural elements. In BF, these changes result in a blockage of the DNA-binding cleft

Substrate specificities of inteins investigated by QuickDrop-cassette mutagenesis

Inteins catalyze self-excision from host precursor proteins while concomitantly ligating the flanking substrates (exteins) with a peptide bond. Noncatalytic extein residues near the splice junctions, such as the residues at the -1 and +2 positions, often strongly influence the protein-splicing efficiency. The substrate specificities of inteins have not been studied for many inteins. We developed a convenient mutagenesis platform termed "QuickDrop"-cassette mutagenesis for investigating the influences of 20 amino acid types at the -1 and +2 positions of different inteins. We elucidated 17 different profiles of the 20 amino acid dependencies across different inteins. The substrate specificities will accelerate our understanding of the structure-function relationship at the splicing junctions for broader applications of inteins in biotechnology and molecular biosciences.Peer reviewe

Mycobacterium tuberculosis ClpP Proteases Are Co-transcribed but Exhibit Different Substrate Specificities

PMCID: PMC3613350This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Global asthma prevalence in adults: findings from the cross-sectional world health survey

<p>Abstract</p> <p>Background</p> <p>Asthma is a major cause of disability, health resource utilization and poor quality of life world-wide. We set out to generate estimates of the global burden of asthma in adults, which may inform the development of strategies to address this common disease.</p> <p>Methods</p> <p>The World Health Survey (WHS) was developed and implemented by the World Health Organization in 2002-2003. A total of 178,215 individuals from 70 countries aged 18 to 45 years responded to questions related to asthma and related symptoms. The prevalence of asthma was based on responses to questions relating to self-reported doctor diagnosed asthma, clinical/treated asthma, and wheezing in the last 12 months.</p> <p>Results</p> <p>The global prevalence rates of doctor diagnosed asthma, clinical/treated asthma and wheezing in adults were 4.3%, 4.5%, and 8.6% respectively, and varied by as much as 21-fold amongst the 70 countries. Australia reported the highest rate of doctor diagnosed, clinical/treated asthma, and wheezing (21.0%, 21.5%, and 27.4%). Amongst those with clinical/treated asthma, almost 24% were current smokers, half reported wheezing, and 20% had never been treated for asthma.</p> <p>Conclusions</p> <p>This study provides a global estimate of the burden of asthma in adults, and suggests that asthma continues to be a major public health concern worldwide. The high prevalence of smoking remains a major barrier to combating the global burden of asthma. While the highest prevalence rates were observed in resource-rich countries, resource-poor nations were also significantly affected, posing a barrier to development as it stretches further the demands of non-communicable diseases.</p

Restricting digital sites of dissent: commercial social media and free expression

The widespread use of commercial social media platforms by protesters and activists has enhanced protest mobilisation and reporting but it has placed social media providers in the intermediary role as facilitators of dissent and has thereby created new challenges. Companies like Google and Facebook are increasingly restricting content that is published on or distributed through their platforms; they have been subject to obstruction by governments; and their services have been at the core of large-scale data collection and surveillance. This article analyses and categorises forms of infrastructure-based restrictions on free expression and dissent. It shows how private intermediaries have been incorporated into state-led content policies; how they set their own standards for legitimate online communication and intervene accordingly; and how state-based actions and commercial self-regulation intersect in the specific area of online surveillance. Based on a broad review of cases, it situates the role of social media in the wider trend of the privatisation of communications policy and the complex interplay between state-based regulation and commercial rule-making

Greater risk of incident asthma cases in adults with Allergic Rhinitis and Effect of Allergen Immunotherapy: A Retrospective Cohort Study

Asthma and rhinitis are often co-morbid conditions. As rhinitis often precedes asthma it is possible that effective treatment of allergic rhinitis may reduce asthma progression. The aim of our study is to investigate history of allergic rhinitis as a risk factor for asthma and the potential effect of allergen immunotherapy in attenuating the incidence of asthma. Hospital-referred non-asthmatic adults, aged 18–40 years between 1990 and 1991, were retrospectively followed up until January and April 2000. At the end of follow up, available subjects were clinically examined for asthma diagnosis and history of allergen specific immunotherapy, second-hand smoking and the presence of pets in the household. A total of 436 non-asthmatic adults (332 subjects with allergic rhinitis and 104 with no allergic rhinitis nor history of atopy) were available for final analyses. The highest OR (odds ratio) associated with a diagnosis of asthma at the end of follow-up was for the diagnosis of allergic rhinitis at baseline (OR, 7.8; 95%CI, 3.1–20.0 in the model containing the covariates of rhinitis diagnosis, sex, second-hand smoke exposure, presence of pets at home, family history of allergic disorders, sensitization to Parietaria judaica; grass pollen; house dust mites; Olea europea: orchard; perennial rye; and cat allergens). Female sex, sensitization to Parietaria judaica and the presence of pets in the home were also significantly predictive of new onset asthma in the same model. Treatment with allergen immunotherapy was significantly and inversely related to the development of new onset asthma (OR, 0.53; 95%CI, 0.32–0.86). In the present study we found that allergic rhinitis is an important independent risk factor for asthma. Moreover, treatment with allergen immunotherapy lowers the risk of the development of new asthma cases in adults with allergic rhinitis

Head CT is of limited diagnostic value in critically ill patients who remain unresponsive after discontinuation of sedation

<p>Abstract</p> <p>Background</p> <p>Prolonged sedation is common in mechanically ventilated patients and is associated with increased morbidity and mortality. We sought to determine the diagnostic value of head computed tomography (CT) in mechanically ventilated patients who remain unresponsive after discontinuation of sedation.</p> <p>Methods</p> <p>A retrospective review of adult (age >18 years of age) patients consecutively admitted to the medical intensive care unit of a tertiary care medical center. Patients requiring mechanical ventilation for management of respiratory failure for longer than 72 hours were included in the study group. A group that did not have difficulty with awakening was included as a control.</p> <p>Results</p> <p>The median time after sedation was discontinued until a head CT was performed was 2 days (interquartile range 1.375–2 days). Majority (80%) of patients underwent head CT evaluation within the first 48 hours after discontinuation of sedation. Head CT was non-diagnostic in all but one patient who had a small subarachnoid hemorrhage. Twenty-five patients (60%) had a normal head CT. Head CT findings did not alter the management of any of the patients. The control group was similar to the experimental group with respect to demographics, etiology of respiratory failure and type of sedation used. However, while 37% of subjects in the control group had daily interruption of sedation, only 19% in the patient group had daily interruption of sedation (p < 0.05).</p> <p>Conclusion</p> <p>In patients on mechanical ventilation for at least 72 hours and who remain unresponsive after sedative discontinuation and with a non-focal neurologic examination, head CT is performed early and is of very limited diagnostic utility. Routine use of daily interruption of sedation is used in a minority of patients outside of a clinical trial setting though it may decrease the frequency of unresponsiveness from prolonged sedation and the need for head CT in patients mechanically ventilated for a prolonged period.</p