An anatomical substrate for experience-dependent plasticity of the rat barrel field cortex.

The objective of this study was to examine the influence of sensory experience on the synaptic circuitry of the cortex. For this purpose, the quantitative distribution of the overall and of the gamma-aminobutyric acid (GABA) population of synaptic contacts was investigated in each layer of the somatosensory barrel field cortex of rats which were sensory deprived from birth by continuously removing rows of whiskers. Whereas there were no statistically significant changes in the quantitative distribution of the overall synaptic population, the number and proportion of GABA-immunopositive synaptic contacts were profoundly altered in layer IV of the somatosensory cortex of sensory-deprived animals. These changes were attributable to a specific loss of as many as two-thirds of the GABA contacts targeting dendritic spines. Thus, synaptic contacts made by GABA terminals in cortical layer IV and, in particular, those targeting dendritic spines represent a structural substrate of experience-dependent plasticity. Furthermore, since in this model of cortical plasticity the neuronal receptive-field properties are known to be affected, we propose that the inhibitory control of dendritic spines is essential for the elaboration of these functional properties.

Selective vulnerability of late-generated dopaminergic neurons of the substantia nigra in weaver mutant mice.

In homozygous weaver (wv/wv) mutant mice, nearly 50% of the dopaminergic substantia nigra neurons degenerate by postnatal day 20. We have now determined that the total number of dopaminergic neurons in the ventral midbrains of a litter of obligatory homozygous weaver pups and a litter of normal wild-type control pups indicates that no significant differences are present between groups at birth. To test the hypothesis that the subsequent degeneration of these neurons is linked to their time of origin, [3H]thymidine autoradiography was combined with tyrosine hydroxylase immunocytochemistry to construct neurogenetic timetables on postnatal day 20 in wild-type mice and weaver homozygotes. Both groups have the same span of neurogenesis but have statistically different proportions of neurons generated on specific days. In wild-type mice, more than half of the dopaminergic neurons originate on or after embryonic day 12. In contrast, over two-thirds of the surviving dopaminergic neurons in homozygous weaver mice originate on or before embryonic day 11. Our data suggest that the weaver gene does not interfere with the generation of dopaminergic neurons, but it preferentially kills late-generated dopaminergic neurons between birth and postnatal day 20.

Targeted disruption of the surfactant protein B gene disrupts surfactant homeostasis, causing respiratory failure in newborn mice.

Surfactant protein B (SP-B) is an 8.7-kDa, hydrophobic protein that enhances the spreading and stability of surfactant phospholipids in the alveolus. To further assess the role of SP-B in lung function, the SP-B gene was disrupted by homologous recombination in murine mouse embryonic stem cells. Mice with a single mutated SP-B allele (+/-) were unaffected, whereas homozygous SP-B -/- offspring died of respiratory failure immediately after birth. Lungs of SP-B -/- mice developed normally but remained atelectatic in spite of postnatal respiratory efforts. SP-B protein and mRNA were undetectable and tubular myelin figures were lacking in SP-B -/- mice. Type II cells of SP-B -/- mice contained no fully formed lamellar bodies. While the abundance of SP-A and SP-C mRNAs was not altered, an aberrant form of pro-SP-C, 8.5 kDa, was detected, and fully processed SP-C peptide was markedly decreased in lung homogenates of SP-B -/- mice. Ablation of the SP-B gene disrupts the routing, storage, and function of surfactant phospholipids and proteins, causing respiratory failure at birth.

Lymphocytes selected in allogeneic thymic epithelium mediate dominant tolerance toward tissue grafts of the thymic epithelium haplotype.

Athymic mice grafted at birth with allogeneic thymic epithelium (TE) from day 10 embryos before hematopoietic cell colonization reconstitute normal numbers of T cells and exhibit full life-long tolerance to skin grafts of the TE haplotype. Intravenous transfers of splenic cells, from these animals to adult syngeneic athymic recipients, reconstitute T-cell compartments and the ability to reject third-party skin grafts. The transfer of specific tolerance to skin grafts of the TE donor strain, however, is not observed in all reconstituted recipients, and the fraction of nontolerant recipients increases with decreasing numbers of cells transferred. Furthermore, transfers of high numbers of total or CD4+ T cells from TE chimeras to T-cell receptor-anti-H-Y antigen transgenic immunocompetent syngeneic hosts specifically hinder the rejection of skin grafts of the TE haplotype that normally occurs in such recipients. These observations demonstrate (i) that mice tolerized by allogeneic TE and bearing healthy skin grafts harbor peripheral immunocompetent T cells capable of rejecting this very same graft; and (ii) that TE selects for regulatory T cells that can inhibit effector activities of graft-reactive cells.

Academie to atelier : the artistic education of American women in nineteenth-century Paris

This paper puts forth an alternate reading of the artistic climate in late nineteenth-century Paris than that which has traditionally been suggested. I propose that the expansion of creative opportunity during this time reveals a climate of communal support, consent, and progressive reform for women artists, rather than a struggle to undermine central (masculine) control, as many scholars have claimed. Specifically, I explore the work of American expatriates living in Paris, including but not limited to Cecilia Beaux, Anna Klumpke, Alice Kellogg, and Ellen Day Hale. The birth of the private academy in Paris offered women the chance to develop their artistic ability and assert their independence. The Académie Julian in particular provided a comparatively accepting and progressive environment where American women studying abroad could study from the nude model, receive proper training, and explore their full creative potential. Through an examination of a) these women’s self-portraits, and b) depictions of them painted by their contemporaries – both male and female – I further investigate the artistic education of American women in the highly-gendered cultural milieu of late nineteenth-century France.

Immunohistochemical evidence of synaptic retraction, cytoarchitectural remodeling, and cell death in the inner retina of the rat model of Oygen-Induced Retinopathy (OIR)

Purpose. Postnatal exposure to hyperoxia destroys the plexiform layers of the neonatal rat retina, resulting in significant electroretinographic anomalies. The purpose of this study was to identify the mechanisms at the origin of this loss. Methods. Sprague-Dawley (SD) and Long Evans (LE) rats were exposed to hyperoxia from birth to postnatal day (P) 6 or P14 and from P6 to P14, after which rats were euthanatized at P6, P14, or P60. Results. At P60, synaptophysin staining confirmed the lack of functional synaptic terminals in SD (outer plexiform layer [OPL]) and LE (OPL and inner plexiform layer [IPL]) rats. Uneven staining of ON-bipolar cell terminals with mGluR6 suggests that their loss could play a role in OPL thinning. Protein kinase C(PKC)-α and recoverin (rod and cone ON-bipolar cells, respectively) showed a lack of dendritic terminals in the OPL with disorganized axonal projections in the IPL. Although photoreceptor nuclei appeared intact, a decrease in bassoon staining (synaptic ribbon terminals) suggests limited communication to the inner retina. Findings were significantly more pronounced in LE rats. An increase in TUNEL-positive cells was observed in LE (inner nuclear layer [INL] and outer nuclear layer [ONL]) and SD (INL) rats after P0 to P14 exposure (425.3%, 102.2%, and 146.3% greater than control, respectively [P < 0.05]). Conclusions. Results suggest that cell death and synaptic retraction are at the root of OPL thinning. Increased TUNEL-positive cells in the INL confirm that cells die, at least in part, because of apoptosis. These findings propose a previously undescribed mechanism of cell death and synaptic retraction that are likely at the origin of the functional consequences of hyperoxia.

The outburst decay of the low magnetic field magnetar SGR 0418+5729

We report on the long-term X-ray monitoring of the outburst decay of the low magnetic field magnetar SGR 0418+5729 using all the available X-ray data obtained with RXTE, Swift, Chandra, and XMM-Newton observations from the discovery of the source in 2009 June up to 2012 August. The timing analysis allowed us to obtain the first measurement of the period derivative of SGR 0418+5729: ˙ P = 4(1) × 10−15 s s−1, significant at a ∼3.5σ confidence level. This leads to a surface dipolar magnetic field of Bdip 6 × 1012 G. This measurement confirms SGR 0418+5729 as the lowest magnetic field magnetar. Following the flux and spectral evolution from the beginning of the outburst up to ∼1200 days, we observe a gradual cooling of the tiny hot spot responsible for the X-ray emission, from a temperature of ∼0.9 to 0.3 keV. Simultaneously, the X-ray flux decreased by about three orders of magnitude: from about 1.4 × 10−11 to 1.2 × 10−14 erg s−1 cm−2. Deep radio, millimeter, optical, and gamma-ray observations did not detect the source counterpart, implying stringent limits on its multi-band emission, as well as constraints on the presence of a fossil disk. By modeling the magneto-thermal secular evolution of SGR 0418+5729, we infer a realistic age of ∼550 kyr, and a dipolar magnetic field at birth of ∼1014 G. The outburst characteristics suggest the presence of a thin twisted bundle with a small heated spot at its base. The bundle untwisted in the first few months following the outburst, while the hot spot decreases in temperature and size. We estimate the outburst rate of low magnetic field magnetars to be about one per year per galaxy, and we briefly discuss the consequences of such a result in several other astrophysical contexts.

The imprint of the crustal magnetic field on the thermal spectra and pulse profiles of isolated neutron stars

Isolated neutron stars (NSs) show a bewildering variety of astrophysical manifestations, presumably shaped by the magnetic field strength and topology at birth. Here, using state-of-the-art calculations of the coupled magnetic and thermal evolution of NSs, we compute the thermal spectra and pulse profiles expected for a variety of initial magnetic field configurations. In particular, we contrast models with purely poloidal magnetic fields to models dominated by a strong internal toroidal component. We find that, while the former displays double-peaked profiles and very low pulsed fractions, in the latter, the anisotropy in the surface temperature produced by the toroidal field often results in a single pulse profile, with pulsed fractions that can exceed the 50–60 per cent level even for perfectly isotropic local emission. We further use our theoretical results to generate simulated ‘observed’ spectra, and show that blackbody (BB) fits result in inferred radii that can be significantly smaller than the actual NS radius, even as low as ∼1–2 km for old NSs with strong internal toroidal fields and a high absorption column density along their line of sight. We compute the size of the inferred BB radius for a few representative magnetic field configurations, NS ages and magnitudes of the column density. Our theoretical results are of direct relevance to the interpretation of X-ray observations of isolated NSs, as well as to the constraints on the equation of state of dense matter through radius measurements.

The Soul never sleeps, 1761

Three-page handwritten composition in English beginning, "One would think that by this Time our opponents should be pretty near silenced..." The document is a draft with edits and struck-through words and the verso includes the handwritten title, "Argument at a forensic Disputation 1761."

[Forensic dispute on thinking and the soul], undated

One folio-sized leaf containing a handwritten essay responding to an unidentified opponent's claims that "thinking is essential to the soul." The response begins with the introduction, "In the consideration of this question, I shall only examine one or two of the most material objects of our antagonist." The verso is inscribed: "2d Forensic. not read."

The Portuguese Version of the Placental Paradigm Questionnaire at the Third Trimester of Pregnancy

The purpose of this article is to present the adaptation and factorial validation of the Placental Paradigm Questionnaire (PPQ) for the Portuguese population. Method: The original PPQ was translated into Portuguese (designated as ‘Questionário do Paradigma Placentário’, QPP) and then back-translated into English; the Portuguese and the back-translated versions were evaluated by a panel of experts. The participants were 189 pregnant Portuguese women, interviewed twice while waiting for sonogram examinations. At first, between 20 and 24 weeks of gestation, an Informed Consent was obtained as well as sociodemographic information. Between 28 and 36 weeks of gestation, participants answered the QPP. Results: The principal components analysis showed items to load mainly on two factors: in factor one, loads ranged between .778 and .522, while in factor 2, loads ranged between .658 and .421. Accordingly, two subscales of prenatal maternal orientation to motherhood were considered: (1) Facilitator Factor (α = .815) and Regulator Factor (α = .770). Conclusion: Overall, these data suggest that the Portuguese version of the QPP is a reliable and valid measure for the assessment of prenatal orientation for motherhood. In the future, QPP measurements will allow to relate maternal orientation to motherhood with other variables of psychic organisation in pregnancy and after birth.

Aging and the governance of the healthcare system in Japan. Bruegel Working Paper 2014/14, December 2014

Japan is the most rapidly aging country in the world. This is evidence that the social security system, which consists of the pension system, healthcare system and other programmes, has been working well. The population is shrinking because of a falling birth rate. It is expected that the population will fall from 128 million in 2010 to 87 million in 2060. During this period, the ratio of people aged 65 or over will rise from 23 percent to 39.9 percent. Japan’s age dependency ratio was 62 in 2013, the highest among advanced nations. It is expected to rise sharply to 94 in 2050 (see Figure 1 on page 4). A total reform of the Japanese social security system, therefore, is inevitable. From the point of view of fiscal reconstruction, reform of the healthcare system is the most important issue. The biggest problem in the healthcare system is that both the funding system and the care-delivery system are extremely fragmented. The government is planning its reform of the healthcare system based on the principle of integration. Other advanced economies could learn from the Japanese experience.

Imperial legacy? The EU's Developmental Model and the Crisis of the European Periphery. CES Papers - Open Forum #19, 2013-2014

The high hopes for rapid convergence of Eastern and Southern EU member states are increasingly being disappointed. With the onset of the Eurocrisis convergence has given way to divergence in the southern members, and many Eastern members have made little headway in closing the development gap. The EU´s performance compares unfavourably with East Asian success cases as well as with Western Europe´s own rapid catch-up to the USA after 1945. Historical experience indicates that successful catch up requires that less-developed economies to some extent are allowed to free-ride on an open international economic order. However, the EU´s model is based on the principle of a level-playing field, which militates against such a form of economic integration. The EU´s developmental model thus contrasts with the various strategies that have enabled successful catch up of industrial latecomers. Instead the EU´s current approach is more and more reminiscent of the relations between the pre-1945 European empires and their dependent territories. One reason for this unfortunate historical continuity is that the EU appears to have become entangled in its own myths. In the EU´s own interpretation, European integration is a peace project designed to overcome the almost continuous warfare that characterised the Westphalian system. As the sovereign state is identified as the root cause of all evil, any project to curtail its room of manoeuvre must ultimately benefit the common good. Yet, the existence of a Westphalian system of nation states is a myth. Empires and not states were the dominant actors in the international system for at least the last three centuries. If anything, the dawn of the age of the sovereign state in Western Europe occurred after 1945 with the disintegration of the colonial empires and thus historically coincided with the birth of European integration.

A Pan-European District for the European Elections? The Rise and Fall of the Duff Proposal for the Electoral Reform of the European Parliament. Bruges Political Research Papers 44/2015.

The aim of the present article is to understand the dynamics underlying the birth, the development and the eventual failure of the Duff proposal of 2009-2012, an ambitious attempt to change the provisions governing the elections for the European Parliament. In particular, the way agenda-setting on electoral reform is shaped in the European Union will be analysed, trying to understand if the current stalemate on the issue can be explained in light of factors specific to the EU. The report presented by liberal MEP Andrew Duff at the beginning of the seventh legislature called on Member States to gather a Convention, in order to introduce fundamental improvements in the way Members of the European Parliament are elected. Among the envisaged changes, the creation of a pan-European constituency to elect twenty-five Members on transnational lists represented the most controversial issue. After having analysed its main elements, the path of the Duff report from the committee of Constitutional Affairs (AFCO) to the plenary will be analysed. It will be concluded that a sharp contrast exists between the way electoral issues are raised in the AFCO committee and the way the Parliament as a whole deals with them. Moreover, diverging interests between national delegations inside groups seem to play a decisive role in hampering electoral reform. While further research is needed to corroborate the present findings, the analysis of the Duff proposal appears to shed light on the different barriers that ensure electoral reform is taken off the agenda of the Union, and on the relative weight each of them carries.

Development of the Commonwealth of Puerto Rico /

"Address by Hon. Luis Muñoz Marín, former Governor of Puerto Rico, on 114th anniversary of birth of Puerto Rican patriot Luis Muñoz Rivera, July 17, 1973, Barranquitas, Puerto Rico."