29,801 research outputs found

    A Role of Myocardin Related Transcription Factor-A (MRTF-A) in Scleroderma Related Fibrosis.

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    In scleroderma (systemic sclerosis, SSc), persistent activation of myofibroblast leads to severe skin and organ fibrosis resistant to therapy. Increased mechanical stiffness in the involved fibrotic tissues is a hallmark clinical feature and a cause of disabling symptoms. Myocardin Related Transcription Factor-A (MRTF-A) is a transcriptional co-activator that is sequestered in the cytoplasm and translocates to the nucleus under mechanical stress or growth factor stimulation. Our objective was to determine if MRTF-A is activated in the disease microenvironment to produce more extracellular matrix in progressive SSc. Immunohistochemistry studies demonstrate that nuclear translocation of MRTF-A in scleroderma tissues occurs in keratinocytes, endothelial cells, infiltrating inflammatory cells, and dermal fibroblasts, consistent with enhanced signaling in multiple cell lineages exposed to the stiff extracellular matrix. Inhibition of MRTF-A nuclear translocation or knockdown of MRTF-A synthesis abolishes the SSc myofibroblast enhanced basal contractility and synthesis of type I collagen and inhibits the matricellular profibrotic protein, connective tissue growth factor (CCN2/CTGF). In MRTF-A null mice, basal skin and lung stiffness was abnormally reduced and associated with altered fibrillar collagen. MRTF-A has a role in SSc fibrosis acting as a central regulator linking mechanical cues to adverse remodeling of the extracellular matrix

    Insights into pneumococcal pneumonia using lung aspirates and nasopharyngeal swabs collected from pneumonia patients in The Gambia.

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    We investigated the pathogenesis of pneumococcal pneumonia using clinical specimens collected for pneumonia surveillance in The Gambia. Lung aspirates and nasopharyngeal swabs from 31 patients were examined by culture, qPCR, whole genome sequencing, serotyping, and reverse transcription qPCR. Five lung aspirates cultured pneumococci, with a matching strain identified in the nasopharynx. Three virulence genes including ply (pneumolysin) were upregulated >20-fold in the lung compared with the nasopharynx. Nasopharyngeal pneumococcal density was higher in pediatric pneumonia patients compared with controls (p <0.0001). Findings suggest that changes in pneumococcal gene expression occurring in the lung environment may be important in pathogenesis

    Rhizosphere dynamics of inoculated cyanobacteria and their growth-promoting role in rice crop

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    Nitrogen fixing cyanobacteria are the predominant flora in waterlogged paddy fields which contribute significantly towards nitrogen budgeting in these ecosystems. Their establishment and role in plant growth promotion and soil microbial activity is poorly known. Under greenhouse conditions, pots were inoculated with one of a set of twenty cyanobacterial strains isolated from the rhizosphere of diverse rice and wheat varieties. Several strains established in the soil and persisted up to the harvest stage in soil and roots, significantly enhancing soil microbial biomass carbon, available nitrogen, and related soil microbiological parameters, and increased grain yields and grain weight. This can help in selecting promising strains for developing carrier-based inoculants to promote the growth of crop and soil microflora, leading to enhanced soil fertility and crop yields

    Do red deer stags (Cervus elaphus) use roar fundamental frequency (F0) to assess rivals?

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    It is well established that in humans, male voices are disproportionately lower pitched than female voices, and recent studies suggest that this dimorphism in fundamental frequency (F0) results from both intrasexual (male competition) and intersexual (female mate choice) selection for lower pitched voices in men. However, comparative investigations indicate that sexual dimorphism in F0 is not universal in terrestrial mammals. In the highly polygynous and sexually dimorphic Scottish red deer Cervus elaphus scoticus, more successful males give sexually-selected calls (roars) with higher minimum F0s, suggesting that high, rather than low F0s advertise quality in this subspecies. While playback experiments demonstrated that oestrous females prefer higher pitched roars, the potential role of roar F0 in male competition remains untested. Here we examined the response of rutting red deer stags to playbacks of re-synthesized male roars with different median F0s. Our results show that stags’ responses (latencies and durations of attention, vocal and approach responses) were not affected by the F0 of the roar. This suggests that intrasexual selection is unlikely to strongly influence the evolution of roar F0 in Scottish red deer stags, and illustrates how the F0 of terrestrial mammal vocal sexual signals may be subject to different selection pressures across species. Further investigations on species characterized by different F0 profiles are needed to provide a comparative background for evolutionary interpretations of sex differences in mammalian vocalizations

    Determining Training Needs for Cloud Infrastructure Investigations using I-STRIDE

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    As more businesses and users adopt cloud computing services, security vulnerabilities will be increasingly found and exploited. There are many technological and political challenges where investigation of potentially criminal incidents in the cloud are concerned. Security experts, however, must still be able to acquire and analyze data in a methodical, rigorous and forensically sound manner. This work applies the STRIDE asset-based risk assessment method to cloud computing infrastructure for the purpose of identifying and assessing an organization's ability to respond to and investigate breaches in cloud computing environments. An extension to the STRIDE risk assessment model is proposed to help organizations quickly respond to incidents while ensuring acquisition and integrity of the largest amount of digital evidence possible. Further, the proposed model allows organizations to assess the needs and capacity of their incident responders before an incident occurs.Comment: 13 pages, 3 figures, 3 tables, 5th International Conference on Digital Forensics and Cyber Crime; Digital Forensics and Cyber Crime, pp. 223-236, 201

    Roaring high and low: composition and possible functions of the Iberian stag's vocal repertoire

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    We provide a detailed description of the rutting vocalisations of free-ranging male Iberian deer (Cervus elaphus hispanicus, Hilzheimer 1909), a geographically isolated and morphologically differentiated subspecies of red deer Cervus elaphus. We combine spectrographic examinations, spectral analyses and automated classifications to identify different call types, and compare the composition of the vocal repertoire with that of other red deer subspecies. Iberian stags give bouts of roars (and more rarely, short series of barks) that are typically composed of two different types of calls. Long Common Roars are mostly given at the beginning or at the end of the bout, and are characterised by a high fundamental frequency (F0) resulting in poorly defined formant frequencies but a relatively high amplitude. In contrast, Short Common Roars are typically given in the middle or at the end of the bout, and are characterised by a lower F0 resulting in relatively well defined vocal tract resonances, but low amplitude. While we did not identify entirely Harsh Roars (as described in the Scottish red deer subspecies (Cervus elaphus scoticus), a small percentage of Long Common Roars contained segments of deterministic chaos. We suggest that the evolution of two clearly distinct types of Common Roars may reflect divergent selection pressures favouring either vocal efficiency in high pitched roars or the communication of body size in low-pitched, high spectral density roars highlighting vocal tract resonances. The clear divergence of the Iberian red deer vocal repertoire from those of other documented European red deer populations reinforces the status of this geographical variant as a distinct subspecies

    Early Galactic Evolution of Carbon, Nitrogen and Oxygen

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    We present results on carbon, nitrogen, and oxygen abundances for a sample of unevolved metal-poor stars with metallicities in the range -0.3< [Fe/H]< -3. Oxygen abundances derived from different indicators are compared showing consistently that in the range 0.3 >[Fe/H]>-3.0, the [O/Fe] ratio increases from approximately 0 to 1. We find a good agreement between abundances based on the forbidden line, the OH and IR triplet lines when gravities based on Hipparcos} parallaxes are considered for the sample stars. Gravities derived from LTE ionization balance in metal-poor stars with [Fe/H]< -1 are likely too low, and could be responsible for an underestimation of the oxygen abundances derived using the [OI] line. [C/Fe] and [N/Fe] ratios appear to be constant, independently of metallicity, in the same range. However, they show larger scatter than oxygen at a given metallicity, which could reflect the larger variety of stellar production sites for these other elements.Comment: 10 pages, 3 figures, To appear in the proceedings of the conference "The Chemical Evolution of The Milky Way: Stars versus Clusters", eds. F. Matteucci and F. Giovannelli, Vulcano, Italy, September 20-24 199

    Assessing Professionalism: A theoretical framework for defining clinical rotation assessment criteria

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    Although widely accepted as an important graduate competence, professionalism is a challenging outcome to define and assess. Clinical rotations provide an excellent opportunity to develop student professionalism through the use of experiential learning and effective feedback, but without appropriate theoretical frameworks, clinical teachers may find it difficult to identify appropriate learning outcomes. The adage “I know it when I see it” is unhelpful in providing feedback and guidance for student improvement, and criteria that are more specifically defined would help students direct their own development. This study sought first to identify how clinical faculty in one institution currently assess professionalism, using retrospective analysis of material obtained in undergraduate teaching and faculty development sessions. Subsequently, a faculty workshop was held in which a round-table type discussion sought to develop these ideas and identify how professionalism assessment could be improved. The output of this session was a theoretical framework for teaching and assessing professionalism, providing example assessment criteria and ideas for clinical teaching. This includes categories such as client and colleague interaction, respect and trust, recognition of limitations, and understanding of different professional identities. Each category includes detailed descriptions of the knowledge, skills, and behaviors expected of students in these areas. The criteria were determined by engaging faculty in the development of the framework, and therefore they should represent a focused development of criteria already used to assess professionalism, and not a novel and unfamiliar set of assessment guidelines. The faculty-led nature of this framework is expected to facilitate implementation in clinical teaching

    The diagnostic accuracy of a single CEA blood test in detecting colorectal cancer recurrence: Results from the FACS trial

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    Objective: To evaluate the diagnostic accuracy of a single CEA (carcinoembryonic antigen) blood test in detecting colorectal cancer recurrence. Background: Patients who have undergone curative resection for primary colorectal cancer are typically followed up with scheduled CEA testing for 5 years. Decisions to investigate further (usually by CT imaging) are based on single test results, reflecting international guidelines. Methods: A secondary analysis was undertaken of data from the FACS trial (two arms included CEA testing). The composite reference standard applied included CT-CAP imaging, clinical assessment and colonoscopy. Accuracy in detecting recurrence was evaluated in terms of sensitivity, specificity, likelihood ratios, predictive values, time-dependent area under the ROC curves, and operational performance when used prospectively in clinical practice are reported. Results: Of 582 patients, 104 (17.9%) developed recurrence during the 5 year follow-up period. Applying the recommended threshold of 5µg/L achieves at best 50.0% sensitivity (95% CI: 40.1-59.9%); in prospective use in clinical practice it would lead to 56 missed recurrences (53.8%; 95% CI: 44.2-64.4%) and 89 false alarms (56.7% of 157 patients referred for investigation). Applying a lower threshold of 2.5µg/L would reduce the number of missed recurrences to 36.5% (95% CI: 26.5-46.5%) but would increase the false alarms to 84.2% (924/1097 referred). Some patients are more prone to false alarms than others – at the 5µg/L threshold, the 89 episodes of unnecessary investigation were clustered in 29 individuals. Conclusion: Our results demonstrated very low sensitivity for CEA, bringing to question whether it could ever be used as an independent triage test. It is not feasible to improve the diagnostic performance of a single test result by reducing the recommended action threshold because of the workload and false alarms generated. Current national and international guidelines merit re-evaluation and options to improve performance, such as making clinical decisions on the basis of CEA trend, should be further assessed
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