Role of protein kinase C-delta in the regulation of collagen gene expression in scleroderma fibroblasts

Working with cultured dermal fibroblasts derived from control individuals and patients with systemic sclerosis (SSc), we have examined the effects of protein kinase C-delta (PKC-delta) on type I collagen biosynthesis and steady-state levels of COL1A1 and COL3A1 mRNAs. Rottlerin, a specific inhibitor of PKC-delta, exerted a powerful, dose-dependent inhibition of type I and type III collagen gene expression in normal and SSc cells. Optimal rottlerin concentrations caused a 70-90% inhibition of type I collagen production, a \u3e80% reduction in COL1A1 mRNA, and a \u3e70% reduction in COL3A1 mRNA in both cell types. In vitro nuclear transcription assays and transient transfections with COL1A1 promoter deletion constructs demonstrated that rottlerin profoundly reduced COL1A1 transcription and that this effect required a 129-bp promoter region encompassing nucleotides -804 to -675. This COL1A1 segment imparted rottlerin sensitivity to a heterologous promoter. Cotransfections of COL1A1 promoter constructs with a dominant-negative PKC-delta expression plasmid showed that suppression of this kinase silenced COL1A1 promoter activity. The results indicate that PKC-delta participates in the upregulation of collagen gene transcription in SSc and suggest that treatment with PKC-delta inhibitors could suppress fibrosis in this disease

Carpool and Bus Matching Program for the University of Texas at Austin

See this work in the Center for Transportation Research Library catalog: https://library.ctr.utexas.edu/Presto/catalogid=5737I.Foreword -- II. Introduction -- III. Survey Procedures and Preliminary Results -- IV. Impact Analysis -- V. Proposed new routes for service in the University Community -- Bibliography -- Appendices.Center for Transportation Researc

Reinventing Public Administration While De-Inventing Administrative Law: Is It Time For An APA For Regulating Outsourced Government Work

Using state-of-the art reinvented public administration, which emphasizes steering rather rowing,2 the DOD outsourced creation of the database to a private firm, BeNow, Inc. In the process of reinventing its public administration the U.S. is de-inventing administrative law. More importantly, perhaps, it is doing so by default, that is, without serious and substantial public discussion and political debate on whether cost-effectiveness and other values associated with reinvented public administration should trump the norms embodied in administrative law. The readiness to accept the reinventers\u27 vision of a government that works better and costs less is all the more striking in view of the nation\u27s epic post-World War II struggle to tame the federal bureaucracy

Clinical Diagnosis of Placenta Accreta and Clinicopathological Outcomes

Objective To investigate the association between the intraoperative diagnosis of placenta accreta at the time of cesarean hysterectomy and pathological diagnosis. Study Design This is a retrospective cohort study of all patients undergoing cesarean hysterectomy for suspected placenta accreta from 2000 to 2016 at Barnes-Jewish Hospital. The primary outcome was the presence of invasive placentation on the pathology report. We estimated predictive characteristics of clinical diagnosis of placenta accreta using pathological diagnosis as the correct diagnosis. Results There were 50 cesarean hysterectomies performed for suspected abnormal placentation from 2000 to 2016. Of these, 34 (68%) had a diagnosis of accreta preoperatively and 16 (32%) were diagnosed intraoperatively at the time of cesarean delivery. Two patients had no pathological evidence of invasion, corresponding to a false-positive rate of 4% (95% confidence interval [CI]: 0.5%, 13.8%) and a positive predictive value of 96% (95% CI: 86.3%, 99.5%). There were no differences in complications among patients diagnosed intraoperatively compared with those diagnosed preoperatively. Conclusion Most patients undergoing cesarean hysterectomy for placenta accreta do have this diagnosis confirmed on pathology. However, since the diagnosis of placenta accreta was made intraoperatively in nearly a third of cesarean hysterectomies, intraoperative vigilance is required as the need for cesarean hysterectomy may not be anticipated preoperatively

Three dimensional rotational angiography imaging of double aortic arch vascular ring

Three dimensional (3D) rotational angiography is a technique used increasingly for imaging in congenital heart disease. Here the use of this technique for imaging of double aortic arch vascular ring is described and the advantages of this modality. are discussed. 3D rotational angiography is an excellent tool for imaging of various vascular anomalies. It provides high quality accurate images through a quick and safe procedure.peer-reviewe

A method for encoding clinical datasets with SNOMED CT

<p>Abstract</p> <p>Background</p> <p>Over the past decade there has been a growing body of literature on how the Systematised Nomenclature of Medicine Clinical Terms (SNOMED CT) can be implemented and used in different clinical settings. Yet, for those charged with incorporating SNOMED CT into their organisation's clinical applications and vocabulary systems, there are few detailed encoding instructions and examples available to show how this can be done and the issues involved. This paper describes a heuristic method that can be used to encode clinical terms in SNOMED CT and an illustration of how it was applied to encode an existing palliative care dataset.</p> <p>Methods</p> <p>The encoding process involves: identifying input data items; cleaning the data items; encoding the cleaned data items; and exporting the encoded terms as output term sets. Four outputs are produced: the SNOMED CT reference set; interface terminology set; SNOMED CT extension set and unencodeable term set.</p> <p>Results</p> <p>The original palliative care database contained 211 data elements, 145 coded values and 37,248 free text values. We were able to encode ~84% of the terms, another ~8% require further encoding and verification while terms that had a frequency of fewer than five were not encoded (~7%).</p> <p>Conclusions</p> <p>From the pilot, it would seem our SNOMED CT encoding method has the potential to become a general purpose terminology encoding approach that can be used in different clinical systems.</p

Towards an Intelligent Database System Founded on the SP Theory of Computing and Cognition

The SP theory of computing and cognition, described in previous publications, is an attractive model for intelligent databases because it provides a simple but versatile format for different kinds of knowledge, it has capabilities in artificial intelligence, and it can also function like established database models when that is required. This paper describes how the SP model can emulate other models used in database applications and compares the SP model with those other models. The artificial intelligence capabilities of the SP model are reviewed and its relationship with other artificial intelligence systems is described. Also considered are ways in which current prototypes may be translated into an 'industrial strength' working system

Large-scale features of Pliocene climate: results from the Pliocene Model Intercomparison Project

Climate and environments of the mid-Pliocene warm period (3.264 to 3.025 Ma) have been extensively studied. Whilst numerical models have shed light on the nature of climate at the time, uncertainties in their predictions have not been systematically examined. The Pliocene Model Intercomparison Project quantifies uncertainties in model outputs through a coordinated multi-model and multi-model/data intercomparison. Whilst commonalities in model outputs for the Pliocene are clearly evident, we show substantial variation in the sensitivity of models to the implementation of Pliocene boundary conditions. Models appear able to reproduce many regional changes in temperature reconstructed from geological proxies. However, data/model comparison highlights that models potentially underestimate polar amplification. To assert this conclusion with greater confidence, limitations in the time-averaged proxy data currently available must be addressed. Furthermore, sensitivity tests exploring the known unknowns in modelling Pliocene climate specifically relevant to the high latitudes are essential (e.g. palaeogeography, gateways, orbital forcing and trace gasses). Estimates of longer-term sensitivity to CO2 (also known as Earth System Sensitivity; ESS), support previous work suggesting that ESS is greater than Climate Sensitivity (CS), and suggest that the ratio of ESS to CS is between 1 and 2, with a "best" estimate of 1.5