INTRAVASCULAR ANTI-IGE CHALLENGE IN PERFUSED LUNGS - MEDIATOR RELEASE AND VASCULAR PRESSOR-RESPONSE

Intravascular application of goat anti-rabbit immunoglobulin E (IgE) was used to stimulate parenchymal mast cells in situ in perfused rabbit lungs. Sustained pulmonary arterial pressure rise was evoked in the absence of lung vascular permeability increase and lung edema formation. Early prostaglandin (PG) D2 and histamine release into the perfusate was documented, accompanied by more sustained liberation of cysteinyl leukotrienes (LT), LTB4, and PGI2. The quantities of these inflammatory mediators displayed the following order: histamine > cysteinyl-LT > PGI2 > LTB4 > PGD2. Pressor response and inflammatory mediator release revealed corresponding bell-shaped dose dependencies. Cyclooxygenase inhibition (acetylsalicylic acid) suppressed prostanoid generation, increased LT release, and did not substantially affect pressor response and histamine liberation. BW755 C, a cyclo- and lipoxygenase inhibitor, blocked the release of cysteinyl-LT and markedly reduced the liberation of the other inflammatory mediators as well as the pressor response. The H-1-antagonist clemastine caused a moderate reduction of the anti-IgE-provoked pressure rise. We conclude that intravascular anti-IgE challenge in intact lungs provokes the release of an inflammatory mediator profile compatible with in situ lung parenchymal mast cell activation. Pulmonary hypertension represents the predominant vascular response, presumably mediated by cysteinyl-LT and, to a minor extent, histamine liberation.

Urban housing and the role of 'underclass' processes: the case of Ireland

Rising levels of urban deprivation and a perception that poverty has become more concentrated in such areas and has taken on a qualitatively different character have provoked a variety of popular and academic responses. The potentially most fruitful set of hypotheses focuses on the unintended of weak labour force attachment and social isolation is perceived to lead to behaviour and orientations that contribute to a vicious circle of deprivation. In examining the value of this conceptual framework in the Irish case we proceed by measuring directly the social-psychological factors which ave hypothesized to mediate the 'underclass' process.

A significantly higher level of poverty is found in urban public-sector tenant households. This finding cannot be accounted for entirely by socio-demographic differences. It is the assessment of this net or residual effect that is crucial to an evaluation of vicious circle explanations. Controlling for the critical social-psychological factors we found that net effect was reduced by less than a quarter and concluded that the remaining effect is more plausibly attributed to the role of selection than to underclass processes. Analysis of the changing relationship between urban public-sector tenancy and poverty provides support for this interpretation.

For the main part the distinctiveness of social housing tenants is a consequence of the disadvantages they stiffer in relation to employment opportunities and living standards. Ultimately it is these problems that policy interventions, whatever the level at which they take place, must address.

Neonatal facial and cry responses to invasive and non-invasive procedures

Evaluation of pain in neonates is difficult due to their limited means of communication. The aim was to determine whether behavioural reactions of cry and facial activity provoked by an invasive procedure could be discriminated from responses to non-invasive tactile events. Thirty-six healthy full-term infants (mean age 2.2 h) received 3 procedures in counterbalanced order: intramuscular injection, application of triple dye to the umbilical stub, and rubbing thigh with alcohol. Significant effects of procedure were found for total face activity and latency to face movement. A cluster of facial actions comprised of brow bulging, eyes squeezed shut, deepening of the naso-labial furrow and open mouth was associated most frequently with the invasive procedure. Comparisons between the 2 non-invasive procedures showed more facial activity to thigh swabbing and least to application of triple dye to the umbilical cord. Acoustic analysis of cry showed statistically significant differences across procedures only for latency to cry and cry duration for the group as a whole. However, babies who cried to two procedures showed higher pitch and greater intensity to the injection. There were no significant differences in melody, dysphonation, or jitter. Methodological difficulties for investigators in this area were examined, including criteria for the selection of cries for analysis, and the logical and statistical challenges of contrasting cries induced by different conditions when some babies do not always cry. It was concluded that facial expression, in combination with short latency to onset of cry and long duration of first cry cycle typifies reaction to acute invasive procedures.

Taking as Giving, Appropriation as Access: Transfers of Land Development Rights and China’s Recent Experiments

Economic development at both the domestic and global levels is associated with increasing tensions which are inextricably linked to the meaning and allocation of property rights, which has a great impact on appropriation of resources and may lead to different paths of development. “Taking”-- the appropriation of private land for public needs -- is a typical example that exhibits those tensions, posing a challenge to the conventional conception of property as individualistic and exclusive rights of possession, use, and disposition and to the associated neoliberal model of development. Should the individual landowner be left to bear the cost of a regulatory intervention which endures to the wider benefit of the whole community? How to mitigate the tensions between private ownership and public regulation? If we take the liberal concept of property, then private property seems to be in constant conflict with public interests and wider social concerns. Meanwhile, community, situating between the state and the individuals, and community’s relationship to development rights, have not provoked enough discussion. The paper explores the different ways land development rights might be seen both in Western, essentially common law systems, and in China, especially now and in view of two case studies. An empirical example in Wugang, China reveals the importance of integrating the “community lens” proposed by Roger Cotterrell into studies of the transfer of land development rights. Reading through the community lens, taking could be giving and appropriation could also be access. This approach provides a new perspective to re-evaluate the relationship between legal appropriation and development.

V3 versican isoform alters the behavior of human melanoma cells by interfering with CD44/ErbB-dependent signaling

Versican is a hyaluronan-binding, extracellular chondroitin sulfate proteoglycan produced by several tumor types, including malignant melanoma, which exists as four different splice variants. The short V3 isoform contains the G1 and G3 terminal domains of versican that may potentially interact directly or indirectly with the hyaluronan receptor CD44 and the EGFR, respectively. We have previously described that overexpression of V3 in MeWo human melanoma cells markedly reduces tumor cell growth in vitro and in vivo. In this study we have investigated the signaling mechanism of V3 by silencing the expression of CD44 in control and V3-expressing melanoma cells. Suppression of CD44 had the same effects on cell proliferation and cell migration than those provoked by V3 expression, suggesting that V3 acts through a CD44-mediated mechanism. Furthermore, CD44-dependent hyaluronan internalization was blocked by V3 expression and CD44 silencing, leading to an accumulation of this glycosaminoglycan in the pericellular matrix and to changes in cell migration on hyaluronan. Furthermore, ERK1/2 and p38 activation after EGF treatment were decreased in V3-expressing cells suggesting that V3 may also interact with the EGFR through its G3 domain. The existence of a EGFR/ErbB2 receptor complex able to interact with CD44 was identified in MeWo melanoma cells. V3 overexpression resulted in a reduced interaction between EGFR/ErbB2 and CD44 in response to EGF treatment. Our results indicate that the V3 isoform of versican interferes with CD44 and the CD44-EGFR/ErbB2 interaction, altering the signaling pathways, such as ERK1/2 and p38 MAPK, that regulate cell proliferation and migration.

From Notation to Composition:How in my practice the exploration of notational possibilitieshas led to new compositional opportunities

This paper explores my experiments with computer animated notation. It examines how I turned to
computer animated notation to address issues with static musical notation. In particular looking at
the work of Nancarrow, Cage, Tenney, and how a number of these composers' approaches
presented difficult challenges for traditional musical notation. I then discuss how computer
animated notation can provide some interesting solutions to the notational problems provoked in
these works.
In the second part of the paper I investigate how addressing these notational challenges has led to
new prespectives on the compositional process and has introduced new considerations into my
compositional practice including time as musical material, real-time and multi-nodal interaction
with the score, networked score environments with the possibility of physically distributed
performance, performer feedback and communication, and interaction between notation and other
media including visual media and movement.

Vasoactivity of Rucaparib, a PARP-1 Inhibitor, is a Complex Process that Involves Myosin Light Chain Kinase, P2 Receptors, and PARP Itself

Therapeutic inhibition of poly(ADP-ribose) polymerase (PARP), as monotherapy or to supplement the potencies of other agents, is a promising strategy in cancer treatment. We previously reported that the first PARP inhibitor to enter clinical trial, rucaparib (AG014699), induced vasodilation in vivo in xenografts, potentiating response to temozolomide. We now report that rucaparib inhibits the activity of the muscle contraction mediator myosin light chain kinase (MLCK) 10-fold more potently than its commercially available inhibitor ML-9. Moreover, rucaparib produces additive relaxation above the maximal degree achievable with ML-9, suggesting that MLCK inhibition is not solely responsible for dilation. Inhibition of nitric oxide synthesis using L-NMMA also failed to impact rucaparib's activity. Rucaparib contains the nicotinamide pharmacophore, suggesting it may inhibit other NAD+-dependent processes. NAD+ exerts P2 purinergic receptor-dependent inhibition of smooth muscle contraction. Indiscriminate blockade of the P2 purinergic receptors with suramin abrogated rucaparib-induced vasodilation in rat arterial tissue without affecting ML-9-evoked dilation, although the specific receptor subtypes responsible have not been unequivocally identified. Furthermore, dorsal window chamber and real time tumor vessel perfusion analyses in PARP-1-/- mice indicate a potential role for PARP in dilation of tumor-recruited vessels. Finally, rucaparib provoked relaxation in 70% of patient-derived tumor-associated vessels. These data provide tantalising evidence of the complexity of the mechanism underlying rucaparib-mediated vasodilation.

(Not) Commemorating the First World War and the Somme

In November 2013 the Attorney General of Northern Ireland, John Larkin, suggested the possibility to ending troubles-related historic prosecutions in Northern Ireland. These remarks provoked a considerable reaction, mostly hostile, and while the attorney’s rationale was based largely upon the practical difficulties associated with gathering reliable evidence and securing prosecutions after a lengthy time lag, his suggestion raises the question of whether forgetting would be preferable to remembering when it comes to our contested past. This paper intends to take a different slant on commemoration by exploring in broad terms the theme of ‘not commemorating’. In this regard it will examine the arguments in favour of remembering. Specifically in regard to the case of the memory of the First World War, it will examine the mistaken impression that the commemoration of that conflict was not widespread in independent Ireland during the inter-war years. Finally, it will suggest some of the greatest challenges facing contemporary Northern Irish society in marking the decade of centenaries.

Dark room provocative test and extent of angle closure: an anterior segment OCT study.

PURPOSE: To clarify the risk parameters measured by anterior segment optical coherence tomography (AS-OCT) for elevated intraocular pressures (IOP) provoked by the darkroom test and to provide recommendations for its clinical usage. METHODS: Subjects aged >40 years and whose peripheral anterior chambers were ≤1/4 corneal thickness were recruited. The anterior segment of the eye was imaged in sitting position and under both light and dark conditions and biometry was performed using anterior segment optical coherence tomography. The analyzed parameters were: (1) central anterior chamber depth (ACD); (2) anterior chamber width; (3) pupil diameter; (4) iris curvature; (5) lens thickness; and (6) number of meridians with closed angles (NCA). Then the darkroom test was performed and a positive provocative test result was defined as a rise in IOP ≥8 mm Hg after the test. Statistical analyses included: (1) the difference in parameters between positive and negative eyes; (2) the association between posttest IOP and the parameters; and (3) the difference in parameters between the 2 eyes in subjects with the asymmetric results. RESULTS: A total of 70 subjects were recruited. ACD (P=0.022), NCA in light (P<0.001), and NCA in dark (P<0.001) were different significantly between eyes with positive and negative results. There was a strong association between NCA in dark (r=0.755, P<0.001) and the posttest IOP. Among subjects with asymmetric results between the 2 eyes, the ACD was shallower and the lens thickness was larger in the positive eye. CONCLUSIONS: The posttest IOP is determined by the extent of functionally closed angles in the dark. The test may be useful in the early diagnosis of primary angle closure. At the same time, angle configuration should be evaluated to remove false positive result.

A etnoarqueologia no Brasil: ciência e sociedade no contexto da redemocratização

Dissertação mest., Arqueologia, Universidade do Algarve, 2008

A investigação-acção e a mudança no Movimento da Escola Moderna : um estudo de caso

Tese de mestrado, Ciências da Educação (Formação de Professores), Universidade de Lisboa, Instituto de Educação, 2010

Control and comparison of the antioxidant capacity of beers

The purpose of the present work is to determine the antioxidant capacity (AC) of 27 commercial beers. The AC indicates the degree of protection of a certain organism against oxidative damage provoked by reactive oxygen and nitrogen species. Assays were carried out by the following methods: (i) total radical trapping antioxidant parameter (TRAP); (ii) trolox equivalent antioxidant capacity (TEAC); (iii) trolox equivalent antioxidant capacity (DPPH); (iv) ferric-ion reducing antioxidant parameter (FRAP); (v) cupric reducing antioxidant capacity (CUPRAC); (vi) oxygen radical absorbance capacity (ORAC). Ascorbic acid (AA), gallic acid (GA) and trolox (TR) were used as standards. All beers showed antioxidant power, but a wide range of ACs was observed. The effect of several factors upon these differences was studied. Statistical differences were found between ACs of beers of different colours. ORAC method provided always higher experimental ACs, of significant statistical differences to other assays.

Impact of multi-metals (Cd, Pb and Zn) exposure on the physiology of the yeast Pichia kudriavzevii

Metal contamination of the environment is frequently associated to the presence of two or more metals. This work aimed to study the impact of a mixture of metals (Cd, Pb and Zn) on the physiology of the non-conventional yeast Pichia kudriavzevii. The incubation of yeast cells with 5 mg/l Cd, 10 mg/l Pb and 5 mg/l Zn, for 6 h, induced a loss of metabolic activity (assessed by FUN-1 staining) and proliferation capacity (evaluated by a clonogenic assay), with a small loss of membrane integrity (measured by trypan blue exclusion assay). The staining of yeast cells with calcofluor white revealed that no modification of chitin deposition pattern occurred during the exposure to metal mixture. Extending for 24 h, the exposure of yeast cells to metal mixture provoked a loss of membrane integrity, which was accompanied by the leakage of intracellular components. A marked loss of the metabolic activity and the loss of proliferation capacity were also observed. The analysis of the impact of a single metal has shown that, under the conditions studied, Pb was the metal responsible for the toxic effect observed in the metal mixture. Intracellular accumulation of Pb seems to be correlated with the metals' toxic effects observed.

Estudo sobre viabilidade de produção descentralizada de energia à custa do efeito chaminé

A procura por alternativas ao atual paradigma energético, que se caracteriza por uma predominância indiscutível das fontes combustíveis fósseis, é o motivo primário desta investigação. A energia emitida pelo Sol que chega à Terra diariamente ultrapassa em várias ordens de grandeza a energia que a nossa sociedade atual necessita. O efeito chaminé é uma das formas de aproveitar essa energia. Este efeito tem origem no diferencial de temperaturas existente entre o interior e o exterior de uma chaminé, que provoca um gradiente nas massas volúmicas do fluido entre o interior e o exterior da chaminé, induzindo assim um fluxo de ar. Esta diferença de temperaturas radica na exposição da face exterior da chaminé à radiação solar. No sistema que nos propomos estudar, o ar entra na chaminé por pequenos orifícios situados na sua base, e, ao tomar contacto com as paredes internas da chaminé, aquece desde a temperatura ambiente, Ta, até à temperatura interna, Ti . Este aumento de temperatura torna o ar dentro da chaminé mais “leve” em comparação com o ar mais frio do exterior levando-o a ascender ao longo do interior da chaminé. Este escoamento contém energia cinética que pode, por exemplo, ser transformada em energia elétrica por intermédio de turbinas. A eficiência de conversão da energia será tanto maior quanto menor for a velocidade do ar a jusante da turbina. Esta tecnologia poderá ser instalada de forma descentralizada, como acontece com as atuais centrais concentradoras solares térmicas e fotovoltaicas localizadas na periferia de grandes cidades ou, alternativamente, poderá ser inserida no próprio tecido urbanístico. A investigação demonstra que as dimensões da chaminé, a irradiação e a temperatura do ar são os fatores com maior impacto na potência hidráulica gerada.

A variabilidade no consumo de recursos nos traumatismos crânio-encefálicos

RESUMO - Portugal atravessa um contexto socioeconómico conturbado onde se têm imposto várias reformas, nomeadamente ao nível da Saúde. Atualmente, o financiamento do internamento hospitalar é feito por grupos de diagnóstico homogéneo com base num sistema prospetivo, reunindo os episódios em grupos clinicamente coerentes e homogéneos, de acordo com o consumo de recursos necessário para o seu tratamento, tendo em conta as suas características clínicas. Apesar do objetivo deste sistema de classificação de doentes, é aceite que existe variabilidade no consumo de recursos entre episódios semelhantes, sendo que a mesma variabilidade pode representar uma diferença significativa nos custos de tratamento. Os Traumatismos Cranio-encefálicos são considerados um problema de saúde pública, pelo que os episódios selecionados para este estudo tiveram por base os diagnósticos mais comuns relacionados com esta problemática. Procurou-se estudar a relação entre o consumo esperado e o observado bem como, a forma em que esta relação é influenciada por diferentes variáveis. Para verificar a existência de variabilidade no consumo de recursos, bem como as variáveis mais influentes, foi utilizada a regressão linear e constatou-se que variáveis como a idade, o destino pós-alta e o distrito têm poder explicativo sobre esta relação. Verificou-se igualmente que na sua generalidade as instituições hospitalares são eficientes na prestação de cuidados. Compreender a variabilidade do consumo de recursos e as suas implicações no financiamento poderá suscitar a dúvida se a utilização de GDH será o mais adequado à realidade portuguesa, de forma a ajustar as políticas de saúde, mantendo a eficiência e a qualidade dos cuidados.