Phosphorylation-dependent human immunodeficiency virus type 1 infection and nuclear targeting of viral DNA.

In the replication of human immunodeficiency virus type 1 (HIV-1), gag MA (matrix), a major structural protein of the virus, carries out opposing targeting functions. During virus assembly, gag MA is cotranslationally myristoylated, a modification required for membrane targeting of gag polyproteins. During virus infection, however, gag MA, by virtue of a nuclear targeting signal at its N terminus, facilitates the nuclear localization of viral DNA and establishment of the provirus. We now show that phosphorylation of gag MA on tyrosine and serine prior to and during virus infection facilitates its dissociation from the membrane, thus allowing it to translocate to the nucleus. Inhibition of gag MA phosphorylation either on tyrosine or on serine prevents gag MA-mediated nuclear targeting of viral nucleic acids and impairs virus infectivity. The requirement for gag MA phosphorylation in virus infection is underscored by our finding that a serine/threonine kinase is associated with virions of HIV-1. These results reveal a novel level of regulation of primate lentivirus infectivity.

Do European Union fines deter price-fixing? Bruegel Policy Brief 2013/04, May 2013

The issue: Anti-cartel enforcement is the least controversial of competition policy themes. Agreements to restrict competition such as price fixing or market sharing have obvious negative effects on welfare. Within the European Union, however, industry representatives have increasingly voiced concern that the European Commission applies a too-strict fining policy to enforce anti-cartel law, particularly since the introduction of new guidelines on fines in 2006. Fines are said to be too high, disproportionate and liable to introduce distortions into the market, ultimately leading to higher prices for consumers. It is often argued that more lenient approaches should be followed in crisis times. Policy challenge: High fines for cartel activity could entail costs for society and might be difficult to implement. Nevertheless, there is no case for reducing current levels of EU anti-cartel fines. Fine levels already take the economic crisis into account, and the net present value of fines might prove to be too low to discourage collusion. We estimate that fines might even be not high enough to offset the additional profits yielded by collusion. Fines should be complemented with other measures to increase deterrence, in particular personal sanctions targeting company officers who are responsible for leading the company to commit infringements. In the short term, pressure on decision makers could be increased by reducing the expected duration of investigations.

The Ghost of Deflation Past. CEPS Hi-level Brief, 13 December 2013

This note takes a look at the development of monetary aggregates and debt in the G7 (US, UK, France, Germany, Italy, Canada and Japan), plus non-G7 euro-area countries, which have an important bearing on the future development of price levels. It also discusses the problem of restoring external competitiveness in the weaker euro-area countries without aggravating their debt burden. The key conclusions are i) monetary and debt developments in the G7 countries point to relatively sluggish growth but do not signal deflation risks and ii) the realignment of ‘internal real exchange rates’ in the euro area will most likely come through a rise in prices in Germany (and a few other stronger countries). The lessons learned in the early 1930s have made a come-back of deflation quite unlikely.

Farm-level Capital: Capital positions, structures, the dynamics of farm-level investments, capital accumulation and leverage positions. Factor Markets Working Paper No. 7, October 2011

This Factor Markets Working Paper describes and highlights the key issues of farm capital structures, the dynamics of investments and accumulation of farm capital, and the financial leverage and borrowing rates on farms in selected European countries. Data collected from the Farm Account Data Network (FADN) suggest that the European farming sector uses quite different farm business strategies, capabilities to generate capital revenues, and segmented agricultural loan market regimes. Such diverse business strategies have substantial, and perhaps more substantial than expected, implications for the financial leverage and performance of farms. Different countries adopt different approaches to evaluating agricultural assets, or the agricultural asset markets simply differ substantially depending on the country in question. This has implications for most of the financial indicators. In those countries that have seen rapidly increasing asset prices at the margin, which were revised accordingly in the accounting systems for the whole stock of assets, firm values increased significantly, even though the firms had been disinvesting. If there is an asset price bubble and it bursts, there may be serious knock-on effects for some countries.

Price stabilization and the risk-averse firm

An analytically simple and tractable approach to firm-level welfare analysis of complete and partial mean-preserving price stabilization for producers with general risk-averse preferences facing a stochastic technology is developed. Necessary and sufficient conditions for price stabilization to be welfare enhancing are derived under different assumptions of the producer's preferences and the producer's technology. Existing stabilization results for the risk-averse firm are shown to be corollaries of these more general results.

Efficient developmental mis-targeting by the sporamin NTPP vacuolar signal to plastids in young leaves of sugarcane and Arabidopsis

Plant vacuoles are multi-functional, developmentally varied and can occupy up to 90% of plant cells. The N-terminal propeptide (NTPP) of sweet potato sporamin and the C-terminal propeptide (CTPP) of tobacco chitinase have been developed as models to target some heterologous proteins to vacuoles but so far tested on only a few plant species, vacuole types and payload proteins. Most studies have focused on lytic and protein-storage vacuoles, which may differ substantially from the sugar-storage vacuoles in crops like sugarcane. Our results extend the evidence that NTPP of sporamin can direct heterologous proteins to vacuoles in diverse plant species and indicate that sugarcane sucrose-storage vacuoles (like the lytic vacuoles in other plant species) are hostile to heterologous proteins. A low level of cytosolic NTPP-GFP (green fluorescent protein) was detectable in most cell types in sugarcane and Arabidopsis, but only Arabidopsis mature leaf mesophyll cells accumulated NTPP-GFP to detectable levels in vacuoles. Unexpectedly, efficient developmental mis-trafficking of NTPP-GFP to chloroplasts was found in young leaf mesophyll cells of both species. Vacuolar targeting by tobacco chitinase CTPP was inefficient in sugarcane, leaving substantial cytoplasmic activity of rat lysosomal beta-glucuronidase (GUS) [ER (endoplasmic reticulum)-RGUS-CTPP]. Sporamin NTPP is a promising targeting signal for studies of vacuolar function and for metabolic engineering. Such applications must take account of the efficient developmental mis-targeting by the signal and the instability of most introduced proteins, even in storage vacuoles.

The price elasticity of the Euro to movements in foreign reserves through European Central Bank intevention

The Euro has been used as the largest weighting element in a basket of currencies for forex arrangements adopted by several Central European countries outside the European Union (EU). The paper uses a new time-series approach to examine the relationship between the Euro exchange rate and the level of foreign reserves. It employs Zero-no-zero (ZNZ) patterned vector error-correction (VECM) modelling to investigate Granger causal relations among foreign reserves, the European Monetary Union money supply and the Euro exchange rate. The findings confirm that foreign reserves may influence movements in the Euro's exchange rate. Further, ZNZ patterned VECM modelling with exogenous variables is used to estimate the amount of foreign reserves currently required in order to again achieve a targetted Euro exchange rate

Targeting of a tropomyosin isoform to short microfilaments associated with the Golgi complex

A growing body of evidence suggests that the Golgi complex contains an actin-based filament system. We have previously reported that one or more isoforms from the tropomyosin gene Tm5NM (also known as gamma-Tm), but not from either the alpha- or beta-Tm genes, are associated with Golgi-derived vesicles (Heimann et al., (1999). J. Biol. Chem. 274, 10743-10750). We now show that Tm5NM-2 is sorted specifically to the Golgi complex, whereas Tm5NM-1, which differs by a single alternatively spliced internal exon, is incorporated into stress fibers. Tm5NM-2 is localized to the Golgi complex consistently throughout the G1 phase of the cell cycle and it associates with Golgi membranes in a brefeldin A-sensitive and cytochalasin D-resistant manner. An actin antibody, which preferentially reacts with the ends of microfilaments, newly reveals a population of short actin filaments associated with the Golgi complex and particularly with Golgi-derived vesicles. Tm5NM-2 is also found on these short microfilaments. We conclude that an alternative splice choice can restrict the sorting of a tropomyosin isoform to short actin filaments associated with Golgi-derived vesicles. Our evidence points to a role for these Golgi-associated microfilaments in vesicle budding at the level of the Golgi complex.

Electricity market price spike forecast with data mining techniques

Electricity market price forecast is a changeling yet very important task for electricity market managers and participants. Due to the complexity and uncertainties in the power grid, electricity prices are highly volatile and normally carry with spikes. which may be (ens or even hundreds of times higher than the normal price. Such electricity spikes are very difficult to be predicted. So far. most of the research on electricity price forecast is based on the normal range electricity prices. This paper proposes a data mining based electricity price forecast framework, which can predict the normal price as well as the price spikes. The normal price can be, predicted by a previously proposed wavelet and neural network based forecast model, while the spikes are forecasted based on a data mining approach. This paper focuses on the spike prediction and explores the reasons for price spikes based on the measurement of a proposed composite supply-demand balance index (SDI) and relative demand index (RDI). These indices are able to reflect the relationship among electricity demand, electricity supply and electricity reserve capacity. The proposed model is based on a mining database including market clearing price, trading hour. electricity), demand, electricity supply and reserve. Bayesian classification and similarity searching techniques are used to mine the database to find out the internal relationships between electricity price spikes and these proposed. The mining results are used to form the price spike forecast model. This proposed model is able to generate forecasted price spike, level of spike and associated forecast confidence level. The model is tested with the Queensland electricity market data with promising results. Crown Copyright (C) 2004 Published by Elsevier B.V. All rights reserved.

Reflexive OKN with partial and full field stimulation: Effects of age and light level

We recorded reflexive OKN in ten younger (32.3±5.98 years) and older (65.6±6.53) visually normal subjects under viewing conditions designed to differentiate M-pathway functioning from other pathways. Subjects were required to gaze straight ahead while viewing vertical gratings of either 0.43 or 1.08 cpd, drifting at either 5 or 20°/sec and presented at either 8 or 80% contrast. Gratings were presented as full field stimulation, central stimulation or peripheral (>15°) stimulation. The order of presentation of conditions was pseudo-randomised at two blocked light levels: ‘mesopic’ or twilight conditions (1.8 cdm-2) and ‘photopic’ or full light conditions (71.5 cdm-2). For the partial fields, central stimulation, mesopic light level, lower temporal frequencies (i.e. number of stripes passing per second) each contributed to greater OKN strength as measured by slow-phase velocity (SPV). For full field stimulation, and especially for higher temporal frequencies and low contrast, there was a significant interaction between age group × light level (p = 0.017): SPV diminished much more among the older than the younger group for the twilight condition compared to full light. Such a clear diminution in M-pathway sensitivity revealed by OKN response has important implications for everyday situations like crash avoidance under twilight driving conditions.

Retail restructuring and consumer choice 2:understanding consumer choice at the household level

This paper complements the preceding one by Clarke et al, which looked at the long-term impact of retail restructuring on consumer choice at the local level. Whereas the previous paper was based on quantitative evidence from survey research, this paper draws on the qualitative phases of the same three-year study, and in it we aim to understand how the changing forms of retail provision are experienced at the neighbourhood and household level. The empirical material is drawn from focus groups, accompanied shopping trips, diaries, interviews, and kitchen visits with eight households in two contrasting neighbourhoods in the Portsmouth area. The data demonstrate that consumer choice involves judgments of taste, quality, and value as well as more ‘objective’ questions of convenience, price, and accessibility. These judgments are related to households’ differential levels of cultural capital and involve ethical and moral considerations as well as more mundane considerations of practical utility. Our evidence suggests that many of the terms that are conventionally advanced as explanations of consumer choice (such as ‘convenience’, ‘value’, and ‘habit’) have very different meanings according to different household circumstances. To understand these meanings requires us to relate consumers’ at-store behaviour to the domestic context in which their consumption choices are embedded. Bringing theories of practice to bear on the nature of consumer choice, our research demonstrates that consumer choice between stores can be understood in terms of accessibility and convenience, whereas choice within stores involves notions of value, price, and quality. We also demonstrate that choice between and within stores is strongly mediated by consumers’ household contexts, reflecting the extent to which shopping practices are embedded within consumers’ domestic routines and complex everyday lives. The paper concludes with a summary of the overall findings of the project, and with a discussion of the practical and theoretical implications of the study.

Some further empirical evidence on the impact of oil price changes on petrol prices

This paper analyses the asymmetries in the response of petrol prices to oil price shocks. We show that previous work, based on the determination of asymmetric responses, can be improved upon by allowing for asymmetries in short term dynamics. The paper shows that a significant determinant of the response of petrol prices to oil price changes, is the extent to which petrol price can be seen to have departed from its long run equilibrium level.

The targeting of corticosteroids to inflamed tissues

In recent years, much interest has focused on the beneficial effects of administering potentially harmful therapeutic agents in drug carriers so as to reduce their toxic side effects. Rheumatoid arthritis is a chronic systemic disease with progressive destruction of the Joints and long term patient disability, Corticosteroids have been shown to retard the progression of Joint destruction but are limited in their use due to adverse side effects,This project, following the line of investigation started by other workers, was designed to study the use of microspheres to deliver corticosteroids to inflamed tissues by both the oral and intravenous routes. Hydrocortisone (HC)-loaded albumin microspheres were prepared by three different methods, by direct incorporation of HC within the particles, by indirect incorporation of HC by the enzymatic conversion of hydrocortisone-21-phosphate (H-21-P) to HC within the particles, and by the adsorption of HC onto the surface. HC was also loaded with PLA microspheres. The level of corticosteriod loading and in vitro release from microspheres was determined by HPLC analysis. A reversed-phase, ion-pairing HPLC method was developed to simultaneously measure both HC and H-21-P. The highest level of corticosteroid loading was achieved using the incorporation of H-21-P with enzymatic conversion to HC method. However, HPLC analysis showed only 5% of the incorporated steroid was HC. In vitro release rates of steroid from albumin microspheres showed >95% of incorporated steroid was released within 2 hours of dissolution. Increasing the protein:steroid ratio, and the temperature and duration of microsphere stabilization, had little effect on prolonging drug release. In vivo studies, using the carrageenan-induced rat hind-paw model of inflammation, indicated steroid-incorporated microspheres administered both orally and intraperitoneally were not therapeutically advantageous when compared to equivalent free steroid doses. The ability of orally and intravenously dosed [125I]~albumin microspheres (2.67 μm mean diameter) to accumulate in acutely and chronically inflamed tissues was investigated, The subcutaneous air-pouch was the model of inflammation used, with carrageenan as the inflammatory stimulus. Acute and chronic inflammation was shown to be consistently formed  in pouch tissues in terms of cell infiltration and fluid exudate formation in the pouch cavity. Albumin microspheres were shown to accumulate in the inflamed tissues and pouch fluids after both oral and intravenous administration. Preliminary, confirmatory studies using latex microspheres and quantitation by GPC analysis, also indicated microsphere accumulation in both acutely and chronically inflamed air-pouch tissues. tntl lUr"'poucbtis,sues; The results indicate the uptake and transfer of microspheres across the gastrointestinal tract into the circulation and their migration through disrupted endothelium and basement membranes at the inflamed sites. , .

A heat metering system for energy management on an industrial site

Faced with a future of rising energy costs there is a need for industry to manage energy more carefully in order to meet its economic objectives. A problem besetting the growth of energy conservation in the UK is that a large proportion of energy consumption is used in a low intensive manner in organisations where they would be responsibility for energy efficiency is spread over a large number of personnel who each see only small energy costs. In relation to this problem in the non-energy intensive industrial sector, an application of an energy management technique known as monitoring and targeting (M & T) has been installed at the Whetstone site of the General Electric Company Limited in an attempt to prove it as a means for motivating line management and personnel to save energy. The objective energy saving for which the M & T was devised is very specific. During early energy conservation work at the site there had been a change from continuous to intermittent heating but the maintenance of the strategy was receiving a poor level of commitment from line management and performance was some 5% - 10% less than expected. The M & T is concerned therefore with heat for space heating for which a heat metering system was required. Metering of the site high pressure hot water system posed technical difficulties and expenditure was also limited. This led to a ‘tin-house' design being installed for a price less than the commercial equivalent. The timespan of work to achieve an operational heat metering system was 3 years which meant that energy saving results from the scheme were not observed during the study. If successful the replication potential is the larger non energy intensive sites from which some 30 PT savings could be expected in the UK.

Cross-category demand effects of price promotions

Do promotions in a certain category lead to higher revenues in other categories? If so, to what degree? The answers to these questions are highly relevant for retailers that supply products in different categories. Empirical findings in studies that consider a limited number of categories indicate small promotional cross-category effects. This study develops a framework to determine the impact of price promotions on category revenues that include interdependencies among a substantial number of categories at the category demand level. The own- and cross-category demand effects are moderated by variables such as promotion intensity, category characteristics (own-category effects), and spatial distances between shelf locations (cross-category effects). The empirical results based on daily store-level scanner data show that approximately half of all price promotions expand own-category revenues, especially for categories with deeper supported discounts. There is a high probability (61%) that a price promotion affects sales of at least one other category. The number of categories affected is not greater than two. Moderate evidence supports the existence of cross-promotional effects between categories more closely located in a store.