25 research outputs found
Measuring and Comparing Party Ideology and Heterogeneity
Estimates of party ideological positions in Western Democracies yield useful party-level information, but lack the ability to provide insight into intraparty politics. In this paper, we generate comparable measures of latent individual policy positions from elite survey data which enable analysis of elite-level party ideology and heterogeneity. This approach has advantages over both expert surveys and approaches based on behavioral data, such as roll call voting and is directly relevant to the study of party cohesion. We generate a measure of elite positions for several European countries using a common space scaling approach and demonstrate its validity as a measure of party ideology. We then apply these data to determine the sources of party heterogeneity, focusing on the role of intraparty competition in electoral systems, nomination rules, and party goals. We find that policy-seeking parties and centralized party nomination rules reduce party heterogeneity. While intraparty competition has no effect, the presence of these electoral rules conditions the effect of district magnitude
Novel inhibitors of the calcineurin/NFATc hub - alternatives to CsA and FK506?
The drugs cyclosporine A (CsA) and tacrolimus (FK506) revolutionized organ transplantation. Both compounds are still widely used in the clinic as well as for basic research, even though they have dramatic side effects and modulate other pathways than calcineurin-NFATc, too. To answer the major open question - whether the adverse side effects are secondary to the actions of the drugs on the calcineurin-NFATc pathway - alternative inhibitors were developed. Ideal inhibitors should discriminate between the inhibition of (i) calcineurin and peptidyl-prolyl cis-trans isomerases (PPIases; the matchmaker proteins of CsA and FK506), (ii) calcineurin and the other Ser/Thr protein phosphatases, and (iii) NFATc and other transcription factors. In this review we summarize the current knowledge about novel inhibitors, synthesized or identified in the last decades, and focus on their mode of action, specificity, and biological effects
Simulations of a Therapeutic Proton Beam with FLUKA Monte Carlo Code and Varian Eclipse Proton Planning Software
The sharp dose deposition from protons in a medium has some clear advantageous aspects for use in cancer treatment. When charged particles, for instance protons, traverse matter, most of their energy are deposited at the end of their range, causing a sharp peak, the Bragg peak, at a depth determined by the proton range in the medium. This range is a function of the initial proton energy and of the characteristics of the traversed medium. The purpose of this project has been to apply Monte Carlo software to simulate a proton beam resembling a therapeutic beam, and to study the interactions of this beam in phantoms of various design. The simulations were produced with FLUKA Monte Carlo code version 2011 2b. Further the purpose has been to apply Varian Eclipse proton planning (version 11) software to create treatment plans on similar phantoms, in order to study the differences between a time-effective, clinically optimized tool and an accurate, yet time consuming, Monte Carlo simulation tool. A fundamental criteria for a therapeutic beam is that the beam must have the ability to deliver a homogeneous dose to an extended volume. To meet this criteria, the energy of the applied protons must be spread out in order to create a plateau of dose covering the target volume, which is the tumour with some specified margins. This implies that an otherwise monoenergetic beam needs to be energy modulated in order to produce a weighted energy spectrum, resulting in a spread-out Bragg peak (SOBP). In this project, two different approaches were followed in order to obtain a dose deposition with a flat dose plateau at the desired depth. By (1) passively modulating the beam range by inserting material into the simulated beamline, which is the equivalent of the use of a range modifier positioned in the beamline, and by (2) actively modulating the proton energy from the beam source. The resulting dose distributions from these two approaches showed that the dose falloff at the distal part of the target volume was sharper with the active energy modulation approach than when passively using material to modulate the beam energy. The final goal of this project was obtained by the use of a commercial treatment planning system to produce simple treatment plans, and further; to compare the dose profiles to similar treatment plans created with a Monte Carlo simulated beam and geometry. The overall agreement between the two calculation methods were adequate, especially with respect to dose coverage within the defined target volume. However, when introducing different materials such as bone, air and aluminium into the geometry, the differences between the two methods became apparent and it illustrates the tentative limitations of a fast, clinical optimized, dose planning tool compared with a more accurate and detailed, hence tentatively slower, Monte Carlo simulation tool
Bleomycin hydrolase regulates the release of chemokines important for inflammation and wound healing by keratinocytes
Can morphine interfere in the healing process during chronic stress?
Technological advances, constant pressure, increased qualified demand, and other daily activities present in modern society result in increasingly stressful living conditions for the population. in the short term, the release of stress-related hormones can play a key role in the survival of an organism. However, it is well known that chronic exposure to cortisol can lead to many adverse effects. Several findings show immunological changes in response to chronic exposure to cortisol, in particular in skin integrity, which may interfere with the healing process. Morphine is an immunosuppressive drug, and when it is used chronically, it can lead to an increased incidence of infections and a delay in the healing process. the importance of opiates as analgesics in the medical setting is indisputable. However, there are a limited number of studies in this field. These investigations can provide further understanding of the mechanisms involved in the healing process in morphine-dependent individuals under chronic stress, which is a common condition in modern society. Furthermore, medical prescriptions of opiates are common among terminal patients, who frequently develop decubitus ulcers and bacterial infections. This review is aimed to provide a concise analysis of effects of morphine and stress on the healing process.Associacao Fundo de Incentivo a Pesquisa (AFIP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Universidade Federal de São Paulo UNIFESP, Dept Psicobiol, BR-04024002 São Paulo, BrazilUniversidade Federal de São Paulo UNIFESP, Dept Dermatol, BR-04024002 São Paulo, BrazilUniversidade Federal de São Paulo UNIFESP, Dept Psicobiol, BR-04024002 São Paulo, BrazilUniversidade Federal de São Paulo UNIFESP, Dept Dermatol, BR-04024002 São Paulo, BrazilFAPESP: 11/14462FAPESP: 07/55445-6FAPESP: 98/14303-3Web of Scienc