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Gelsolin (GSN), one of the most abundant actin-binding proteins, is involved in cell motility, shape and metabolism. As a member of the GSN superfamily, GSN is a highly structured protein in eukaryotic cells that can be regulated by calcium concentration, intracellular pH, temperature and phosphatidylinositol-4,5-bisphosphate. GSN plays an important role in cellular mechanisms as well as in different cellular interactions. Because of its participation in immunologic processes and its interaction with different cells of the immune system, GSN is a potential candidate for various therapeutic applications. In this review, we summarise the structure of GSN as well as its regulating and functional roles, focusing on distinct diseases such as Alzheimer's disease, rheumatoid arthritis and cancer. A short overview of GSN as a therapeutic target in today's medicine is also provided.
Combining atmospheric Δ14CO2 data sets from different networks or laboratories requires secure knowledge on their compatibility. In the present study, we compare Δ14CO2 results from the Heidelberg low-level counting (LLC) laboratory to 12 international accelerator mass spectrometry (AMS) laboratories using distributed aliquots of five pure CO2 samples. The averaged result of the LLC laboratory has a measurement bias of –0.3±0.5‰ with respect to the consensus value of the AMS laboratories for the investigated atmospheric Δ14C range of 9.6 to 40.4‰. Thus, the LLC measurements on average are not significantly different from the AMS laboratories, and the most likely measurement bias is smaller than the World Meteorological Organization (WMO) interlaboratory compatibility goal for Δ14CO2 of 0.5‰. The number of intercomparison samples was, however, too small to determine whether the measurement biases of the individual AMS laboratories fulfilled the WMO goal.
To evaluate a computer-assisted point-prevalence survey (CAPPS) for hospital-acquired infections (HAIs).
A 754-bed teaching hospital in the Netherlands.
For the internal validation of a CAPPS for HAIs, 2,526 patients were included. All patient records were retrospectively reviewed in depth by 2 infection control practitioners (ICPs) to determine which patients had suffered an HAI. Preventie van Ziekenhuisinfecties door Surveillance (PREZIES) criteria were used. Following this internal validation, 13 consecutive CAPPS were performed in a prospective study from January to March 2013 to determine weekly, monthly, and quarterly HAI point prevalence. Finally, a CAPPS was externally validated by PREZIES (Rijksinstituut voor Volksgezondheid en Milieu [RIVM], Bilthoven, Netherlands). In all evaluations, discrepancies were resolved by consensus.
In our series of CAPPS, 83% of the patients were automatically excluded from detailed review by the ICP. The sensitivity of the method was 91%. The time spent per hospital-wide CAPPS was ~3 hours. External validation showed a negative predictive value of 99.1% for CAPPS.
CAPPS proved to be a sensitive, accurate, and efficient method to determine serial weekly point-prevalence HAI rates in our hospital.
New radiocarbon calibration curves, IntCal04 and Marine04, have been constructed and internationally ratified to replace the terrestrial and marine components of IntCal98. The new calibration data sets extend an additional 2000 yr, from 0–26 cal kyr BP (Before Present, 0 cal BP = AD 1950), and provide much higher resolution, greater precision, and more detailed structure than IntCal98. For the Marine04 curve, dendrochronologically-dated tree-ring samples, converted with a box diffusion model to marine mixed-layer ages, cover the period from 0–10.5 cal kyr BP. Beyond 10.5 cal kyr BP, high-resolution marine data become available from foraminifera in varved sediments and U/Th-dated corals. The marine records are corrected with site-specific 14C reservoir age information to provide a single global marine mixed-layer calibration from 10.5–26.0 cal kyr BP. A substantial enhancement relative to IntCal98 is the introduction of a random walk model, which takes into account the uncertainty in both the calendar age and the 14C age to calculate the underlying calibration curve (Buck and Blackwell, this issue). The marine data sets and calibration curve for marine samples from the surface mixed layer (Marine04) are discussed here. The tree-ring data sets, sources of uncertainty, and regional offsets are presented in detail in a companion paper by Reimer et al. (this issue).
The radiocarbon calibration curve IntCal04 extends back to 26 cal kyr B P. While several high-resolution records exist beyond this limit, these data sets exhibit discrepancies of up to several millennia. As a result, no calibration curve for the time range 26–50 cal kyr BP can be recommended as yet, but in this paper the IntCal04 working group compares the available data sets and offers a discussion of the information that they hold.
The first meeting of the IntCal04 working group took place at Queen's University Belfast from April 15 to 17, 2002. The participants are listed as co-authors of this report. The meeting considered criteria for the acceptance of data into the next official calibration dataset, the importance of including reliable estimates of uncertainty in both the radiocarbon ages and the cal ages, and potential methods for combining datasets. This preliminary report summarizes the criteria that were discussed, but does not yet give specific recommendations for inclusion or exclusion of individual datasets.
The IntCal04 and Marine04 radiocarbon calibration curves have been updated from 12 cal kBP (cal kBP is here defined as thousands of calibrated years before AD 1950), and extended to 50 cal kBP, utilizing newly available data sets that meet the IntCal Working Group criteria for pristine corals and other carbonates and for quantification of uncertainty in both the 14C and calendar timescales as established in 2002. No change was made to the curves from 0–12 cal kBP. The curves were constructed using a Markov chain Monte Carlo (MCMC) implementation of the random walk model used for IntCal04 and Marine04. The new curves were ratified at the 20th International Radiocarbon Conference in June 2009 and are available in the Supplemental Material at www.radiocarbon.org.
We have measured additional known-age German oak samples in 4 intervals in the 2nd and 1st millennia BC to add to (and to replicate) parts of the international Northern Hemisphere radiocarbon calibration data set. In the 17th, 16th, and 12th centuries BC, our results agree well with IntCal04. In the 14th and 13th centuries BC, however, we observe a significant offset, with our results on average 27 yr older than IntCal04. The previously reported 14C offset between Anatolian juniper trees and central European oaks in the 9th and 8th centuries BC is smaller now, on the basis of our new measurements of German oak, but still evident. In the 17th and 16th centuries BC, the 14C ages from the Anatolian chronology agree well with IntCal04 and our new German oak data.
High-quality data from appropriate archives are needed for the continuing improvement of radiocarbon calibration curves. We discuss here the basic assumptions behind 14C dating that necessitate calibration and the relative strengths and weaknesses of archives from which calibration data are obtained. We also highlight the procedures, problems, and uncertainties involved in determining atmospheric and surface ocean 14C/12C in these archives, including a discussion of the various methods used to derive an independent absolute timescale and uncertainty. The types of data required for the current IntCal database and calibration curve model are tabulated with examples.
The IntCal09 and Marine09 radiocarbon calibration curves have been revised utilizing newly available and updated data sets from 14C measurements on tree rings, plant macrofossils, speleothems, corals, and foraminifera. The calibration curves were derived from the data using the random walk model (RWM) used to generate IntCal09 and Marine09, which has been revised to account for additional uncertainties and error structures. The new curves were ratified at the 21st International Radiocarbon conference in July 2012 and are available as Supplemental Material at www.radiocarbon.org. The database can be accessed at http://intcal.qub.ac.uk/intcal13/.