Libraries and literature in Rome

A chapter of 6,000 words on books, literary culture, and public and private libraries in the ancient city of Rome

Isolation and partial characterisation of acid phosphatase isozymes from dormant oilseed of Corylus avellana L.

The acid phosphatase (orthophosphoric-monoester phosphohydrolase, EC 3.1.3.2) complement from dormant hazel (Corylus avellana L.) seeds was found to exhibit significant electrophoretic heterogeneity partially attributable to the presence of distinct molecular forms. In axiferous tissue, total acid phosphatase activity increased in a biphasic fashion during chilling, a treatment necessary to alleviate seed dormancy. Three acid phosphatase isozymes were isolated from cotyledons of dormant hazel seeds by successive ammonium sulphate precipitation, size-exclusion, Concanavalin A affinity, cation- and anion-exchange chromatographies resulting in 75-, 389- and 191-fold purification (APase1, APase2, APase3, respectively). The three glycosylated isoforms were isolated to catalytic homogeneity as determined by electrophoretic, kinetic and heat-inactivation studies. The native acid phosphatase complement of hazel seeds had an apparent Mr of 81.5±3.5 kDa as estimated by size-exclusion chromatography, while the determined pI values were 5.1 (APase1), 6.9 (APase2) and 7.3 (APase3). The optimum pH for p-nitrophenyl phosphate hydrolysis was pH 3 (APase1), pH 5.6 (APase2) and pH 6 (APase3). The hazel isozymes hydrolysed a variety of phosphorylated substrates in a non-specific manner, exhibiting low Km and the highest specificity constant (Vmax/Km) for pyrophosphate. They were not primary phytases since they could not initiate phytic acid hydrolysis, while APase2 and APase3 had significant phospho-tyrosine phosphatase activity. Inorganic phosphate was a competitive inhibitor, while activity was significantly impaired in the presence of vanadate and fluoride.

Platelet adhesion signalling and the regulation of thrombus formation

Platelets perform a central role in haemostasis and thrombosis. They adhere to subendothelial collagens exposed at sites of blood vessel injury via the glycoprotein (GP) 1b-V-IX receptor complex, GPV1 and integrin alpha(2)beta(1)-These receptors perform distinct functions in the regulation of cell signalling involving non-receptor tyrosine kinases (e.g. Src, Fyn, Lyn, Syk and Btk), adaptor proteins, phospholipase C and lipid kinases such as phosphoinositide 3-kinase. They are also coupled to an increase in cytosolic calcium levels and protein kinase C activation, leading to the secretion of paracrine/autocrine platelet factors and an increase in integrin receptor affinities. Through the binding of plasma fibrinogen and von Willebrand Factor to integrin alphaIIbbeta(3), a platelet thrombus is formed. Although increasing evidence indicates that each of the adhesion receptors GPIb-V-IX and GPV1 and integrins alpha(2)beta(1) and alpha(IIb)beta(3) contribute to the signalling that regulates this process, the individual roles of each are only beginning to be dissected. By contrast, adhesion receptor signalling through platelet endothelial cell adhesion molecule 1 (PECAM-1) is implicated in the inhibition of platelet function and thrombus formation in the healthy circulation. Recent studies indicate that understanding of platelet adhesion signalling mechanisms might enable the development of new strategies to treat and prevent thrombosis.

Some new strategies for the chemical separation of actinides and lanthanides

A future goal in nuclear fuel reprocessing is the conversion or transmutation of the long-lived radioisotopes of minor actinides, such as americium, into short-lived isotopes by irradiation with neutrons. In order to achieve this transmutation, it is necessary to separate the minor actinides(III), [An(Ill)], from the lanthanides(III), [Ln(Ill)], by solvent extraction (partitioning), because the lanthanides absorb neutrons too effectively and hence limit neutron capture by the transmutable actinides. Partitioning using ligands containing only carbon, hydrogen, nitrogen and oxygen atoms is desirable because they are completely incinerable and thus the final volume of waste is minimised [1]. Nitric acid media will be used in the extraction experiments because it is envisaged that the An(III)/Ln(III) separation process could take place after the PUREX process. There is no doubt that the correct design of a molecule that is capable of acting as a ligand or extraction reagent is required for the effective separation of metal ions such as actinides(III) from lanthanides. Recent attention has been directed towards heterocyclic ligands with for the preferential separation of the minor actinides. Although such molecules have a rich chemistry, this is only now becoming sufficiently well understood in relation to the partitioning process [2]. The molecules shown in Figures I and 2 will be the principal focus of this study. Although the examples chosen here are used rather specific, the guidelines can be extended to other areas such as the separation of precious metals [3].

Effects of fat on the properties of halloumi cheese

Halloumi cheese was produced from 11 bovine milks with fat contents of 1.61-4.04%, giving a range of 32-53% fat in dry matter (FDM) in the cheeses. Starter culture and/or microparticulated whey protein (Simplesse((R)) 100(E)) was also added to selected batches of milk. Hardness decreased with increasing FDM, with increase in moisture and with lower pH. On sensory evaluation, there was an increase in preference score with FDM (R-2 = 0.8). Inclusion of microparticulated whey protein may have had a fat mimetic effect, as preference scores otherwise decreased with increasing protein levels (R-2 = 0.75).

Investigating the mechanism of enhanced cytotoxicity of HPMA copolymer-Dox-AGM in breast cancer cells

Recently we have described an HPMA copolymer conjugate carrying both the aromatase inhibitor aminoglutethimide (AGM) and doxorubicin (Dox) as combination therapy. This showed markedly enhanced in vitro cytotoxicity compared to the HPMA copolymer-Dox (FCE28068), a conjugate that demonstrated activity in chemotherapy refractory breast cancer patients during early clinical trials. To better understand the superior activity of HPMA copolymer-Dox-AGM, here experiments were undertaken using MCF-7 and MCF-7ca (aromatase-transfected) breast cancer cell lines to: further probe the synergistic cytotoxic effects of AGM and Dox in free and conjugated form; to compare the endocytic properties of HPMA copolymer-Dox-AGM and HPMA copolymer-Dox (binding, rate and mechanism of cellular uptake); the rate of drug liberation by lysosomal thiol-dependant proteases (i.e. conjugate activation), and also, using immunocytochemistry, to compare their molecular mechanism of action. It was clearly shown that attachment of both drugs to the same polymer backbone was a requirement for enhanced cytotoxicity. FACS studies indicated both conjugates have a similar pattern of cell binding and endocytic uptake (at least partially via a cholesterol-dependent pathway), however, the pattern of enzyme-mediated drug liberation was distinctly different. Dox release from PK1 was linear with time, whereas the release of both Dox and AGM from HPMA copolymer-Dox-AGM was not, and the initial rate of AGM release was much faster than that seen for the anthracycline. Immunocytochemistry showed that both conjugates decreased the expression of ki67. However, this effect was more marked for HPMA copolymer-Dox-AGM and, moreover, only this conjugate decreased the expression of the anti-apoptotic protein bcl-2. In conclusion, the superior in vitro activity of HPMA copolymer-Dox-AGM cannot be attributed to differences in endocytic uptake, and it seems likely that the synergistic effect of Dox and AGM is due to the kinetics of intracellular drug liberation which leads to enhanced activity. (c) 2006 Elsevier B.V All rights reserved.

Multi-satellite observed responses of precipitation and its extremes to interannual climate variability

The consistency of precipitation variability estimated from the multiple satellite-based observing systems is assessed. There is generally good agreement between TRMM TMI, SSM/I, GPCP and AMSRE datasets for the inter-annual variability of precipitation since 1997 but the HOAPS dataset appears to overestimate the magnitude of variability. Over the tropical ocean the TRMM 3B42 dataset produces unrealistic variabilitys. Based upon deseasonalised GPCP data for the period 1998-2008, the sensitivity of global mean precipitation (P) to surface temperature (T) changes (dP/dT) is about 6%/K, although a smaller sensitivity of 3.6%/K is found using monthly GPCP data over the longer period 1989-2008. Over the tropical oceans dP/dT ranges from 10-30%/K depending upon time-period and dataset while over tropical land dP/dT is -8 to -11%/K for the 1998-2008 period. Analyzing the response of the tropical ocean precipitation intensity distribution to changes in T we find the wetter area P shows a strong positive response to T of around 20%/K. The response over the drier tropical regimes is less coherent and varies with datasets, but responses over the tropical land show significant negative relationships over an interannual time-scale. The spatial and temporal resolutions of the datasets strongly influence the precipitation responses over the tropical oceans and help explain some of the discrepancy between different datasets. Consistency between datasets is found to increase on averaging from daily to 5-day time-scales and considering a 1o (or coarser) spatial resolution. Defining the wet and dry tropical ocean regime by the 60th percentile of P intensity, the 5-day average, 1o TMI data exhibits a coherent drying of the dry regime at the rate of -20%/K and the wet regime becomes wetter at a similar rate with warming.

Inner plasma structure of the low-latitude reconnection layer

We report a clear transition through a reconnection layer at the low-latitude magnetopause which shows a complete traversal across all reconnected field lines during northwestward interplanetary magnetic field (IMF) conditions. The associated plasma populations confirm details of the electron and ion mixing and the time history and acceleration through the current layer. This case has low magnetic shear with a strong guide field and the reconnection layer contains a single density depletion layer on the magnetosheath side which we suggest results from nearly field-aligned magnetosheath flows. Within the reconnection boundary layer, there are two plasma boundaries, close to the inferred separatrices on the magnetosphere and magnetosheath sides (Ssp and Ssh) and two boundaries associated with the Alfvén waves (or Rotational Discontinuities, RDsp and RDsh). The data are consistent with these being launched from the reconnection site and the plasma distributions are well ordered and suggestive of the time elapsed since reconnection of the field lines observed. In each sub-layer between the boundaries the plasma distribution is different and is centered around the current sheet, responsible for magnetosheath acceleration. We show evidence for a velocity dispersion effect in the electron anisotropy that is consistent with the time elapsed since reconnection. In addition, new evidence is presented for the occurrence of partial reflection of magnetosheath electrons at the magnetopause current layer.

The relationship between El Niño and the western North Pacific summer climate in a coupled GCM: role of the transition of El Niño decaying phases

This study investigates the impacts of the transition of El Niño decaying phases on the western North Pacific anticyclone (WNPAC) anomalies in the subsequent summer with a coupled GCM. The modeling results suggest that the El Niños with short decaying phases lead to significant WNPAC anomalies in the following summer, which are contributed to mainly by the El Niños followed by La Niñas, in comparison with those not followed by La Niñas. In contrast, the long decaying cases are associated with the disappearance of WNPAC anomalies in the summer. These differences in the WNP circulation anomalies can be explained by the different configurations of simultaneous SSTs in the Indian Ocean and in the central and eastern tropical Pacific: positive SSTs in the former region and negative ones in the latter region constructively induce significant WNPAC anomalies for the short decaying cases, while the roles of positive SSTs in both regions for the long decaying cases work destructively and lead to weak WNP circulation anomalies. Further analysis indicates that the different lengths of El Niño decaying phases are predicted by the strength of Indian Ocean SSTs in the mature winter. The warmer wintertime Indian Ocean SSTs favor the anomalous easterly wind over the western and central equatorial Pacific in the subsequent summer, leading to a short decaying of El Niño. Thus, the strength of wintertime Indian Ocean SSTs is one of the important factors that affect the length of El Niño decaying phase and resultant WNPAC anomalies in the following summer.

The influence of ozone precursor emissions from four world regions on tropospheric composition and radiative climate forcing

Ozone (O3) precursor emissions influence regional and global climate and air quality through changes in tropospheric O3 and oxidants, which also influence methane (CH4) and sulfate aerosols (SO42−). We examine changes in the tropospheric composition of O3, CH4, SO42− and global net radiative forcing (RF) for 20% reductions in global CH4 burden and in anthropogenic O3 precursor emissions (NOx, NMVOC, and CO) from four regions (East Asia, Europe and Northern Africa, North America, and South Asia) using the Task Force on Hemispheric Transport of Air Pollution Source-Receptor global chemical transport model (CTM) simulations, assessing uncertainty (mean ± 1 standard deviation) across multiple CTMs. We evaluate steady state O3 responses, including long-term feedbacks via CH4. With a radiative transfer model that includes greenhouse gases and the aerosol direct effect, we find that regional NOx reductions produce global, annually averaged positive net RFs (0.2 ± 0.6 to 1.7 ± 2 mWm−2/Tg N yr−1), with some variation among models. Negative net RFs result from reductions in global CH4 (−162.6 ± 2 mWm−2 for a change from 1760 to 1408 ppbv CH4) and regional NMVOC (−0.4 ± 0.2 to −0.7 ± 0.2 mWm−2/Tg C yr−1) and CO emissions (−0.13 ± 0.02 to −0.15 ± 0.02 mWm−2/Tg CO yr−1). Including the effect of O3 on CO2 uptake by vegetation likely makes these net RFs more negative by −1.9 to −5.2 mWm−2/Tg N yr−1, −0.2 to −0.7 mWm−2/Tg C yr−1, and −0.02 to −0.05 mWm−2/Tg CO yr−1. Net RF impacts reflect the distribution of concentration changes, where RF is affected locally by changes in SO42−, regionally to hemispherically by O3, and globally by CH4. Global annual average SO42− responses to oxidant changes range from 0.4 ± 2.6 to −1.9 ± 1.3 Gg for NOx reductions, 0.1 ± 1.2 to −0.9 ± 0.8 Gg for NMVOC reductions, and −0.09 ± 0.5 to −0.9 ± 0.8 Gg for CO reductions, suggesting additional research is needed. The 100-year global warming potentials (GWP100) are calculated for the global CH4 reduction (20.9 ± 3.7 without stratospheric O3 or water vapor, 24.2 ± 4.2 including those components), and for the regional NOx, NMVOC, and CO reductions (−18.7 ± 25.9 to −1.9 ± 8.7 for NOx, 4.8 ± 1.7 to 8.3 ± 1.9 for NMVOC, and 1.5 ± 0.4 to 1.7 ± 0.5 for CO). Variation in GWP100 for NOx, NMVOC, and CO suggests that regionally specific GWPs may be necessary and could support the inclusion of O3 precursors in future policies that address air quality and climate change simultaneously. Both global net RF and GWP100 are more sensitive to NOx and NMVOC reductions from South Asia than the other three regions.

Impact of melt ponds on Arctic sea ice simulations from 1990 to 2007

The extent and thickness of the Arctic sea ice cover has decreased dramatically in the past few decades with minima in sea ice extent in September 2007 and 2011 and climate models did not predict this decline. One of the processes poorly represented in sea ice models is the formation and evolution of melt ponds. Melt ponds form on Arctic sea ice during the melting season and their presence affects the heat and mass balances of the ice cover, mainly by decreasing the value of the surface albedo by up to 20%. We have developed a melt pond model suitable for forecasting the presence of melt ponds based on sea ice conditions. This model has been incorporated into the Los Alamos CICE sea ice model, the sea ice component of several IPCC climate models. Simulations for the period 1990 to 2007 are in good agreement with observed ice concentration. In comparison to simulations without ponds, the September ice volume is nearly 40% lower. Sensitivity studies within the range of uncertainty reveal that, of the parameters pertinent to the present melt pond parameterization and for our prescribed atmospheric and oceanic forcing, variations of optical properties and the amount of snowfall have the strongest impact on sea ice extent and volume. We conclude that melt ponds will play an increasingly important role in the melting of the Arctic ice cover and their incorporation in the sea ice component of Global Circulation Models is essential for accurate future sea ice forecasts.

Daidzein, R-(+)equol and S-(-)equol inhibit the invasion of MDA-MB-231 breast cancer cells potentially via the down-regulation of matrix metalloproteinase-2

PURPOSE: Soy isoflavones may inhibit tumor cell invasion and metastasis via their effects on matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs). The current study investigates the effects of daidzein, R- and S-equol on the invasion of MDA-MB-231 human breast cancer cells and the effects of these compounds on MMP/TIMP expression at the mRNA level. METHODS: The anti-invasive effects of daidzein, R- and S-equol (0, 2.5, 10, 50 μM) on MDA-MB-231 cells were determined using the Matrigel invasion assay following 48-h exposure. Effects on MMP-2, MMP-9, TIMP-1 and TIMP-2 expression were assessed using real-time PCR. Chiral HPLC analysis was used to determine intracellular concentrations of R- and S-equol. RESULTS: The invasive capacity of MDA-MB-231 cells was significantly reduced (by approximately 50-60 %) following treatment with 50 μM daidzein, R- or S-equol. Anti-invasive effects were also observed with R-equol at 2.5 and 10 μM though overall equipotent effects were induced by all compounds. Inhibition of invasion induced by all three compounds at 50 μM was associated with the down-regulation of MMP-2, while none of the compounds tested significantly affected the expression levels of MMP-9, TIMP-1 or TIMP-2 at this concentration. Following exposure to media containing 50 μM R- or S-equol for 48-h intracellular concentrations of R- and S-equol were 4.38 ± 1.17 and 3.22 ± 0.47 nM, respectively. CONCLUSION: Daidzein, R- and S-equol inhibit the invasion of MDA-MB-231 human breast cancer cells in part via the down-regulation of MMP-2 expression, with equipotent effects observed for the parent isoflavone daidzein and the equol enantiomers.

The correlation of ULF waves and auroral intensity before, during and after substorm expansion phase onset

We present case studies of the evolution of magnetic wave amplitudes and auroral intensity through the late growth phase and the expansion phase of the substorm cycle. We present strong evidence that substorm-related auroral enhancements are clearly and demonstrably linked to ULF wave amplitudes observed at the same location. In most cases, we find that the highest correlations are observed when the magnetometer time series is advanced in time, indicating that the ULF wave amplitudes start to grow before measured auroral intensities, though interestingly this is not always the case. Further we discuss the four possible reasons that may be able to explain both the timing and the high correlations between these two phenomena, including: a simple coincidence, an artifact of instrumental effects, the response of the ionosphere to magnetic waves and auroral particle precipitation, and finally that ULF waves and auroral particle precipitation are physically linked. We discount coincidence and instrumental effects since in the studies presented here they are unlikely or in general will contribute negligible effects, and we find that the ionospheric response to waves and precipitation can explain some, but not all of the results contained within this paper. Specifically, ionospheric response to substorm waves and auroral precipitation cannot explain that the result that previous studies have shown, that onset of ULF wave activity and the onset of auroral particle precipitation occur at the same time and in the same location. This leaves the possibility that ULF waves and auroral particles are physically linked.