298 research outputs found
Satisfaction with Creativity: A Study of Organizational Characteristics and Individual Motivation
In answering the question of what influences satisfaction with creativity in the workplace, this work takes into account the extent to which the organization supports human aspiration to act creatively. The work throughout reflects a pragmatist approach to creativity and fulfillment, bridging it with needs theory in psychology. The empirical model uses survey data encompassing over 4,000 workers in Italian social enterprises. Results show that satisfaction with creativity is supported, at organizational level, by teamwork, autonomy, domain-relevant competences, as well as by inclusive, fair processes and relationships. At the individual level, satisfaction with creativity is enhanced by the strength of intrinsic initial motivations. The analysis of interaction terms shows that teamwork and workers' initial motivations are complementary in enhancing satisfaction with creativity, while a high degree of domain-relevant competences appears to substitute advice and supervision by superiors in accomplishing the desired level of creative action
Atomic structures of TDP-43 LCD segments and insights into reversible or pathogenic aggregation.
The normally soluble TAR DNA-binding protein 43 (TDP-43) is found aggregated both in reversible stress granules and in irreversible pathogenic amyloid. In TDP-43, the low-complexity domain (LCD) is believed to be involved in both types of aggregation. To uncover the structural origins of these two modes of β-sheet-rich aggregation, we have determined ten structures of segments of the LCD of human TDP-43. Six of these segments form steric zippers characteristic of the spines of pathogenic amyloid fibrils; four others form LARKS, the labile amyloid-like interactions characteristic of protein hydrogels and proteins found in membraneless organelles, including stress granules. Supporting a hypothetical pathway from reversible to irreversible amyloid aggregation, we found that familial ALS variants of TDP-43 convert LARKS to irreversible aggregates. Our structures suggest how TDP-43 adopts both reversible and irreversible β-sheet aggregates and the role of mutation in the possible transition of reversible to irreversible pathogenic aggregation
Tectono-stratigraphic evolution and crustal architecture of the Orphan Basin during North Atlantic rifting
The Orphan Basin is located in the deep offshore of the Newfoundland margin, and it is bounded by the continental shelf to the west, the Grand Banks to the south, and the continental blocks of Orphan Knoll and Flemish Cap to the east. The Orphan Basin formed in Mesozoic time during the opening of the North Atlantic Ocean between eastern Canada and western Iberia–Europe. This work, based on well data and regional seismic reflection profiles across the basin, indicates that the continental crust was affected by several extensional episodes between the Jurassic and the Early Cretaceous, separated by events of uplift and erosion. The preserved tectono-stratigraphic sequences in the basin reveal that deformation initiated in the eastern part of the Orphan Basin in the Jurassic and spread towards the west in the Early Cretaceous, resulting in numerous rift structures filled with a Jurassic–Lower Cretaceous syn-rift succession and overlain by thick Upper Cretaceous to Cenozoic post-rift sediments. The seismic data show an extremely thinned crust (4–16 km thick) underneath the eastern and western parts of the Orphan Basin, forming two sub-basins separated by a wide structural high with a relatively thick crust (17 km thick). Quantifying the crustal architecture in the basin highlights the large discrepancy between brittle extension localized in the upper crust and the overall crustal thinning. This suggests that continental deformation in the Orphan Basin involved, in addition to the documented Jurassic and Early Cretaceous rifting, an earlier brittle rift phase which is unidentifiable in seismic data and a depth-dependent thinning of the crust driven by localized lower crust ductile flow
Binary and Millisecond Pulsars at the New Millennium
We review the properties and applications of binary and millisecond pulsars.
Our knowledge of these exciting objects has greatly increased in recent years,
mainly due to successful surveys which have brought the known pulsar population
to over 1300. There are now 56 binary and millisecond pulsars in the Galactic
disk and a further 47 in globular clusters. This review is concerned primarily
with the results and spin-offs from these surveys which are of particular
interest to the relativity community.Comment: 59 pages, 26 figures, 5 tables. Accepted for publication in Living
Reviews in Relativity (http://www.livingreviews.org
Aptamer-based multiplexed proteomic technology for biomarker discovery
Interrogation of the human proteome in a highly multiplexed and efficient manner remains a coveted and challenging goal in biology. We present a new aptamer-based proteomic technology for biomarker discovery capable of simultaneously measuring thousands of proteins from small sample volumes (15 [mu]L of serum or plasma). Our current assay allows us to measure ~800 proteins with very low limits of detection (1 pM average), 7 logs of overall dynamic range, and 5% average coefficient of variation. This technology is enabled by a new generation of aptamers that contain chemically modified nucleotides, which greatly expand the physicochemical diversity of the large randomized nucleic acid libraries from which the aptamers are selected. Proteins in complex matrices such as plasma are measured with a process that transforms a signature of protein concentrations into a corresponding DNA aptamer concentration signature, which is then quantified with a DNA microarray. In essence, our assay takes advantage of the dual nature of aptamers as both folded binding entities with defined shapes and unique sequences recognizable by specific hybridization probes. To demonstrate the utility of our proteomics biomarker discovery technology, we applied it to a clinical study of chronic kidney disease (CKD). We identified two well known CKD biomarkers as well as an additional 58 potential CKD biomarkers. These results demonstrate the potential utility of our technology to discover unique protein signatures characteristic of various disease states. More generally, we describe a versatile and powerful tool that allows large-scale comparison of proteome profiles among discrete populations. This unbiased and highly multiplexed search engine will enable the discovery of novel biomarkers in a manner that is unencumbered by our incomplete knowledge of biology, thereby helping to advance the next generation of evidence-based medicine
The time course of subsequent hospitalizations and associated costs in survivors of an ischemic stroke in Canada
BACKGROUND: Documentation of the hospitalizations rates following a stroke provides the inputs required for planning health services and to evaluate the economic efficiency of any new therapies. METHODS: Hospitalization rates by cause were examined using administrative data on 18,695 patients diagnosed with ischemic stroke (first or subsequent, excluding transient ischemic attack) in Saskatchewan, Canada between 1990 and 1995. Medical history was available retrospectively to January 1980 and follow-up was complete to March 2000. Analyses evaluated the rate and timing of all-cause and cardiovascular hospitalizations within discrete periods in the five years following the index stroke. Cardiovascular hospitalizations included patients with a primary diagnosis of ischemic stroke, transient ischemic attack, myocardial infarction, stable or unstable angina, heart failure or peripheral arterial disease. RESULTS: One-third (36%) of patients were identified by a hospitalized stroke. Mean age was 70.5 years, 48.0% were male, half had a history of stroke or a transient ischemic attack at the time of their index stroke. Three-quarters of the patients (72.7%) were hospitalized at least once during a mean follow-up of 4.6 years, accruing CAD $24 million in the first year alone. Of all hospitalizations, 20.4% were related to cardiovascular disease and 1.6% to bleeds. In the month following index stroke, 12.5% were admitted, an average of 1.04 times per patient hospitalized. Strokes accounted for 33% of all hospitalizations in the first month. The rate diminished steadily throughout the year and stabilized in the second year when approximately one-third of patients required hospitalization, at a rate of about one hospitalization for every two patient-years. Mean lengths of stay ranged from nine days to nearly 40 days. Close-fitting Weibull functions allow highly specific probability estimates. Other cardiovascular risk factors significantly increased hospitalization rates. CONCLUSION: After stroke, there are frequent hospitalizations accounting for substantial additional costs. Though these rates drop after one year, they remain high over time. The number of other cardiovascular causes of hospitalization confirms that stroke is a manifestation of disseminated atherothrombotic disease
Optimizing substitution matrix choice and gap parameters for sequence alignment
<p>Abstract</p> <p>Background</p> <p>While substitution matrices can readily be computed from reference alignments, it is challenging to compute optimal or approximately optimal gap penalties. It is also not well understood which substitution matrices are the most effective when alignment accuracy is the goal rather than homolog recognition. Here a new parameter optimization procedure, POP, is described and applied to the problems of optimizing gap penalties and selecting substitution matrices for pair-wise global protein alignments.</p> <p>Results</p> <p>POP is compared to a recent method due to Kim and Kececioglu and found to achieve from 0.2% to 1.3% higher accuracies on pair-wise benchmarks extracted from BALIBASE. The VTML matrix series is shown to be the most accurate on several global pair-wise alignment benchmarks, with VTML200 giving best or close to the best performance in all tests. BLOSUM matrices are found to be slightly inferior, even with the marginal improvements in the bug-fixed RBLOSUM series. The PAM series is significantly worse, giving accuracies typically 2% less than VTML. Integer rounding is found to cause slight degradations in accuracy. No evidence is found that selecting a matrix based on sequence divergence improves accuracy, suggesting that the use of this heuristic in CLUSTALW may be ineffective. Using VTML200 is found to improve the accuracy of CLUSTALW by 8% on BALIBASE and 5% on PREFAB.</p> <p>Conclusion</p> <p>The hypothesis that more accurate alignments of distantly related sequences may be achieved using low-identity matrices is shown to be false for commonly used matrix types. Source code and test data is freely available from the author's web site at <url>http://www.drive5.com/pop</url>.</p
Safety of percutaneous aortic valve insertion. A systematic review
<p>Abstract</p> <p>Background</p> <p>The technique of percutaneous aortic valve implantation (PAVI) for the treatment of severe aortic stenosis (AS) has been introduced in 2002. Since then, many thousands such devices have worldwide been implanted in patients at high risk for conventional surgery. The procedure related mortality associated with PAVI as reported in published case series is substantial, although the intervention has never been formally compared with standard surgery. The objective of this study was to assess the safety of PAVI, and to compare it with published data reporting the risk associated with conventional aortic valve replacement in high-risk subjects.</p> <p>Methods</p> <p>Studies published in peer reviewed journals and presented at international meetings were searched in major medical databases. Further data were obtained from dedicated websites and through contacts with manufacturers. The following data were extracted: patient characteristics, success rate of valve insertion, operative risk status, early and late all-cause mortality.</p> <p>Results</p> <p>The first PAVI has been performed in 2002. Because of procedural complexity, the original transvenous approach from 2004 on has been replaced by the transarterial and transapical routes. Data originating from nearly 2700 non-transvenous PAVIs were identified. In order to reduce the impact of technical refinements and the procedural learning curve, procedure related safety data from series starting recruitment in April 2007 or later (n = 1975) were focused on. One-month mortality rates range from 6.4 to 7.4% in transfemoral (TF) and 11.6 to 18.6% in transapical (TA) series. Observational data from surgical series in patients with a comparable predicted operative risk, indicate mortality rates that are similar to those in TF PAVI but substantially lower than in TA PAVI. From all identified PAVI series, 6-month mortality rates, reflecting both procedural risk and mortality related to underlying co-morbidities, range from 10.0-25.0% in TF and 26.1-42.8% in TA series. It is not known what the survival of these patients would have been, had they been treated medically or by conventional surgery.</p> <p>Conclusion</p> <p>Safety issues and short-term survival represent a major drawback for the implementation of PAVI, especially for the TA approach. Results from an ongoing randomised controlled trial (RCT) should be awaited before further using this technique in routine clinical practice. In the meantime, both for safety concerns and for ethical reasons, patients should only be subjected to PAVI within the boundaries of such an RCT.</p
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