C3-symmetric peptide scaffolds are functional mimetics of trimeric CD40L.

Interaction between CD40, a member of the tumor necrosis factor receptor (TNFR) superfamily, and its ligand CD40L, a 39-kDa glycoprotein, is essential for the development of humoral and cellular immune responses. Selective blockade or activation of this pathway provides the ground for the development of new treatments against immunologically based diseases and malignancies. Like other members of the TNF superfamily, CD40L monomers self-assemble around a threefold symmetry axis to form noncovalent homotrimers that can each bind three receptor molecules. Here, we report on the structure-based design of small synthetic molecules with C3 symmetry that can mimic CD40L homotrimers. These molecules interact with CD40, compete with the binding of CD40L to CD40, and reproduce, to a certain extent, the functional properties of the much larger homotrimeric soluble CD40L. Architectures based on rigid C3-symmetric cores may thus represent a general approach to mimicking homotrimers of the TNF superfamily.

Relative price riddles in international business cycle theory: Are transport costs the explanation?

We study relative price behavior in an international business cyclemodel with specialization in production, in which a goods marketfriction is introduced through transport costs. The transporttechnology allows for flexible transport costs. We analyze whetherthis extension can account for the striking differences betweentheory and data as far as the moments of terms of trade and realexchange rates are concerned. We find that transport costs increaseboth the volatility of the terms of trade and the volatility of thereal exchange rate. However, unless the transport technology isspecified by a Leontief technology, transport costs do not resolvethe quantitative discrepancies between theory and data. Asurprising result is that transport costs may actually lower thepersistence of the real exchange rate, a finding that is in contrastto much of the emphasis of the empirical literature.

Consumer Advisory Bulletin, Iowans Are Eligible for $1 Million in Prescription Drug Refunds, January 2008

The Attorney General’s Consumer Protection Division receives hundreds of calls and consumer complaints every year. Follow these tips to avoid unexpected expense and disappointments. This record is about: Iowans Are Eligible for $1 Million in Prescription Drug Refunds

Hommes et femmes: sommes-nous tous égaux face à la douleur [Are there differences between men and women with pain?].

An increasing number of articles are published on the differences about pain in men and women. These differences seem to be due to the sex, the biological dimension of the person, and to the gender, which is the role given to that person in a given social and culture environment. The pain prevalence is higher in women, its threshold and tolerance are lower. The pain interpretation, its perception and the coping is also different in men and women. Finally doctors translate and treat pain differently. This article proposes some explanations on these differences which should help us to treat this frequent and noxious symptom for the quality of life in a better way.

Are Americans' musical preferences more omnivores today?

Although we found a general trend favouring the omnivorousness thesis, as soon as we adjusted it to a set of structural factors and consumers tastes it was clear that this was caused by elitist inclusive omnivores who had increased the scope of their tastes. In general, younger cohorts were becoming less omnivorous, nevertheless, they were also becoming more educated and had greater to higher levels of inc ome, making the youth moreomnivorous. As expected, upscale consumers set limits on their popular taste: musicalgenres, whose audiences had educational levels below the mean profile were less preferredby upscale respondents. In spite of this, as time passed, some popular brows gained socialstatus.

How political parties, rather than member-states, are building the European Union

Political party formation and coalition building in the European Parliament is being a driving force for making governance of the highly pluralistic European Union relatively effective and consensual. In spite of successive enlargements and the very high number of electoral partiesobtaining representation in the European Union institutions, the number of effective European Political Groups in the European Parliament has decreased from the first direct election in 1979 to the fifth in 1999. The formal analysis of national party¹s voting power in different Europeanparty configurations can explain the incentives for national parties to join large European Political Groups instead of forming smaller nationalistic groupings. Empirical evidence shows increasing cohesion of European Political Groups and an increasing role of the European Parliament in EU inter-institutional decision making. As a consequence of this evolution, intergovernmentalism is being replaced with federalizing relations. The analysis can support positive expectations regarding the governability of the European Union after further enlargements provided that new member states have party systems fitting the European PoliticalGroups.

How binding are legal limits? Transitions from temporary to permanent work in Spain

This paper studies the duration pattern of xed-term contracts and the determinantsof their conversion into permanent ones in Spain, where the share of xed-termemployment is the highest in Europe. We estimate a duration model for temporaryemployment, with competing risks of terminating into permanent employment versusalternative states, and exible duration dependence. We nd that conversion rates aregenerally below 10%. Our estimated conversion rates roughly increase with tenure,with a pronounced spike at the legal limit, when there is no legal way to retain theworker on a temporary contract. We argue that estimated di¤erences in conversionrates across categories of workers can stem from di¤erences in worker outside optionsand thus the power to credibly threat to quit temporary jobs.

The determinants of pricing in pharmaceuticals: Are U.S. prices really higher than those of Canada?

This paper studies price determination in pharmaceutical markets using data for 25 countries, six years and a comprehensive list of products from the MIDAS IMS database. We show that market power and the quality of the product has a significantly positive impact of prices. The nationality of the producer appears to have a small and often insignificant impact on prices, which suggests that countries which regulates prices have relatively little power to do it in a way that advances narrow national interest. We produce a theoretical explanation for this phenomenon based on the fact that low negotiated prices in a country would have a knock-on effect in other markets, and is thus strongly resisted by producers.Another key finding is that the U.S. has prices that are not significantly higher than those of countries with similar income levels. This, together with the former observation on the effect of the nationality of producers casts doubt on the ability of countries to pursue "free-riding" regulation.

Iodine-131-labeled MAb F(ab')2 fragments are more efficient and less toxic than intact anti-CEA antibodies in radioimmunotherapy of large human colon carcinoma grafted in nude mice.

During one week, beginning 18 days after transplantation, nude mice bearing human colon carcinoma ranging from 115 to 943 mm3 (mean 335 mm3) were treated by repeated intravenous injections of either iodine-131-(131I) labeled intact antibodies or 131I-labeled corresponding F(ab')2 fragments of a pool of four monoclonal antibodies (MAbs) directed against distinct epitopes of carcinoembryonic antigen (CEA). Complete tumor remission was observed in 8 of 10 mice after therapy with F(ab')2 and 6 of the animals survived 10 mo in good health. In contrast, after treatment with intact MAbs, tumors relapsed in 7 of 8 mice after remission periods of 1 to 3.5 mo despite the fact that body weight loss and depression of peripheral white blood cells, symptoms of radiation toxicity, and the calculated radiation doses for liver, spleen, bone, and blood were increased or equal in these animals as compared to mice treated with F(ab')2.

Are these classical business cycles?

The aim of this paper is to test formally the classical business cyclehypothesis, using data from industrialized countries for the timeperiod since 1960. The hypothesis is characterized by the view that the cyclical structure in GDP is concentrated in the investment series: fixed investment has typically a long cycle, while the cycle in inventory investment is shorter. To check the robustness of our results, we subject the data for 15 OECD countries to a variety of detrending techniques. While the hypothesis is not confirmed uniformly for all countries, there is a considerably high number for which the data display the predicted pattern. None of the countries shows a pattern which can be interpreted as a clear rejection of the classical hypothesis.

Are changes in education important for the wage premium and unemployment?

A generalized rise in unemployment rates for both college and high-schoolgraduates, a widening education wage premium, and a sharp increase incollege education participation are characteristic features of thetransformations of the U.S. labor market between 1970 and 1990. This paperinvestigates the interactions between these changes in the labor marketand in educational attainment. First, it develops an equilibrium searchand matching model of the labor market where education is endogenouslydetermined. Second, calibrated versions of the model are used to studyquantitatively whether either a skill-biased change in technology or amismatch shock can explain the above facts. The skill-biased shock accountsfor a considerable part of the changes but fails to produce the increasein unemployment for the educated labor force. The mismatch shock explainsinstead much of the change in the four variables, including the wage premium.

Are agent-based simulations robust? The wholesale electricity trading case

Agent-based computational economics is becoming widely used in practice. This paperexplores the consistency of some of its standard techniques. We focus in particular on prevailingwholesale electricity trading simulation methods. We include different supply and demandrepresentations and propose the Experience-Weighted Attractions method to include severalbehavioural algorithms. We compare the results across assumptions and to economic theorypredictions. The match is good under best-response and reinforcement learning but not underfictitious play. The simulations perform well under flat and upward-slopping supply bidding,and also for plausible demand elasticity assumptions. Learning is influenced by the number ofbids per plant and the initial conditions. The overall conclusion is that agent-based simulationassumptions are far from innocuous. We link their performance to underlying features, andidentify those that are better suited to model wholesale electricity markets.

Are there vascular density gradients along myocardial laser channels?

BACKGROUND: Clinical studies suggest that transmyocardial laser revascularization may improve regional blood flow of the subendocardial layer. The vascular growth pattern of laser channels was analyzed. METHODS: Twenty pigs were randomized to undergo ligation of left marginal arteries (n = 5), to undergo transmyocardial laser revascularization of the left lateral wall (n = 5), to undergo both procedures (n = 5) or to a control group (n = 5). All the animals were sacrificed after 1 month. Computed morphometric analysis of vascular density of the involved area was expressed as number of vascular structures per square millimeter (+/-1 standard deviation). RESULTS: The vascular density of the scar tissue of the laser channel was significantly increased in comparison with myocardial infarction alone: 49.6+/-12.8/mm2 versus 25.5+/-8.6/mm2 (p < 0.0001). The vascular densities of subendocardial and subepicardial channel areas were similar: 52.9+/-16.8/mm2 versus 46.3+/-13.6/mm2 (p = 0.41). The area immediately adjacent to the channels showed a vascular density similar to that of normal tissue: 6.02+/-1.7/mm2 versus 5.2+/-1.9/mm2 (p = 0.08). In the infarction + transmyocardial laser revascularization group, the channels were indistinguishable from infarction scar. CONCLUSIONS: Scars of transmyocardial laser revascularization channels exhibit an increased vascular density in comparison with scar tissue of myocardial infarction, which does not extend into their immediate vicinity. There was no vascular density gradient along the longitudinal axis of the channels.