Therapeutic potential of selective superoxide dismutase mimetics

Selective superoxide dismutase (SOD) mimetics are potentially useful in pathological conditions in which there is an overproduction of the superoxide anion O-2.(-). These pathological conditions include inflammation, ischemia/reperfusion, shock, various cardiovascular disorders, amyotrophic lateral sclerosis (ALS) and other neurodegenerative disorders. A major step forward in this field was the development of small-molecule selective SOD mimetics that penetrate cell membranes, These selective SOD mimetics catalytically remove O-2.(-) without interfering with nitric oxide (NO), peroxynitrite (ONOO-) or other radicals such as hydroxyl radical or hydrogen peroxide (H2O2). These selective SOD mimetics (SC-52608, SC-55858, M-40403 and M-40401) have been shown to have benefits in animal models of inflammation, ischemia/reperfusion, shock, thrombosis and diabetes. The next challenge with selective SOD mimetics is to develop therapeutic potential into therapeutic agents.

The Galilean turn in population ecology

The standard mathematical models in population ecology assume that a population's growth rate is a function of its environment. In this paper we investigate an alternative proposal according to which the rate of change of the growth rate is a function of the environment and of environmental change. We focus on the philosophical issues involved in such a fundamental shift in theoretical assumptions, as well as on the explanations the two theories offer for some of the key data such as cyclic populations. We also discuss the relationship between this move in population ecology and a similar move from first-order to second-order differential equations championed by Galileo and Newton in celestial mechanics.

Politics, Commerce, and Colonization in Angola at the Turn of the Eighteenth Century

Dissertação apresentada para cumprimento dos requisitos necessários à obtenção do grau de Mestre em História Moderna e dos Descobrimentos

Sensory turn. Quando o sujeito se torna o centro da História da Arte

Nas últimas décadas, as ciências sociais e humanas têm despertado para a acção modeladora das estruturas sobre a percepção humana. O debate académico sobre o relativismo cultural dos modelos de percepção tem levado investigadores das várias áreas a debruçarem-se sobre o estudo dos sentidos. Correntes disciplinares como a antropologia ou história dos sentidos vêm sintetizando a dimensão estrutural e fenomenológica, a partir da compreensão do carácter biológico e cultural da experiência sensorial. Nesse sentido, tem emergido uma nova história da arte que contraria as últimas décadas de predomínio da linguística e semiótica, em função da compreensão da performance das imagens ligada à percepção sensorial. Questiona-se o totalitarismo que o método iconográfico/iconológico de Panofsky tem encontrado na historiografia da arte, a partir da ideia de que as imagens antes de um significado são uma acção, antes de uma função são um uso.

Elevated resource availability sufficient to turn opportunistic into virulent fish pathogens.

There is mounting evidence that organic or inorganic enrichment of aquatic environments increases the risk of infectious diseases, with disease agents ranging from helminth parasites to fungal, bacterial, and viral pathogens. The causal link between microbial resource availability and disease risk is thought to be complex and, in the case of so-called "opportunistic pathogens," to involve additional stressors that weaken host resistance (e.g., temperature shifts or oxygen deficiencies). In contrast to this perception, our experiment shows that the link between resource levels and infection of fish embryos can be very direct: increased resource availability can transform benign microbial communities into virulent ones. We find that embryos can be harmed before further stresses (e.g., oxygen depletion) weaken them, and treatment with antibiotics and fungicides cancels the detrimental effects. The changed characteristics of symbiotic microbial communities could simply reflect density-dependent relationships or be due to a transition in life-history strategy. Our findings demonstrate that simple microhabitat changes can be sufficient to turn "opportunistic" into virulent pathogens.

Lipoxin agonists: turn right! to path of resolving neutrophil

An impressive array of cellular and molecular adaptive responses achieves homeostasis. The inflammatory reaction is an adaptive response triggered by an insult to culminate into the overt cardinal signs of inflammation, eventually leading to resolution and returning the organism back to its original centered state. This article focuses on some aspects of the lipoxin A4 signaling pathway during the resolution phase, to better understand molecular mechanisms by which a neutrophil directs an inflammatory reaction to switch off and resume homeostasis. Defining the resolution state of a neutrophil at the molecular level will aid in treatments of diseases that are associated with an exaggerated and uncontrolled inflammation.

Guidelines for the Conversion of Urban Four-Lane Undivided Roadways to Three-Lane Two-Way Left-turn Lane Facilities, April 2001

Four-lane undivided roadways in urban areas can experience a degradation of service and/or safety as traffic volumes increase. In fact, the existence of turning vehicles on this type of roadway has a dramatic effect on both of these factors. The solution identified for these problems is typically the addition of a raised median or two-way left-turn lane (TWLTL). The mobility and safety benefits of these actions have been proven and are discussed in the “Past Research” chapter of this report along with some general cross section selection guidelines. The cost and right-of-way impacts of these actions are widely accepted. These guidelines focus on the evaluation and analysis of an alternative to the typical four-lane undivided cross section improvement approach described above. It has been found that the conversion of a four-lane undivided cross section to three lanes (i.e., one lane in each direction and a TWLTL) can improve safety and maintain an acceptable level of service. These guidelines summarize the results of past research in this area (which is almost nonexistent) and qualitative/quantitative before-and-after safety and operational impacts of case study conversions located throughout the United States and Iowa. Past research confirms that this type of conversion is acceptable or feasible in some situations but for the most part fails to specifically identify those situations. In general, the reviewed case study conversions resulted in a reduction of average or 85th percentile speeds (typically less than five miles per hour) and a relatively dramatic reduction in excessive speeding (a 60 to 70 percent reduction in the number of vehicles traveling five miles per hour faster than the posted speed limit was measured in two cases) and total crashes (reductions between 17 to 62 percent were measured). The 13 roadway conversions considered had average daily traffic volumes of 8,400 to 14,000 vehicles per day (vpd) in Iowa and 9,200 to 24,000 vehicles per day elsewhere. In addition to past research and case study results, a simulation sensitivity analysis was completed to investigate and/or confirm the operational impacts of a four-lane undivided to three-lane conversion. First, the advantages and disadvantages of different corridor simulation packages were identified for this type of analysis. Then, the CORridor SIMulation (CORSIM) software was used x to investigate and evaluate several characteristics related to the operational feasibility of a four-lane undivided to three-lane conversion. Simulated speed and level of service results for both cross sections were documented for different total peak-hour traffic, access densities, and access-point left-turn volumes (for a case study corridor defined by the researchers). These analyses assisted with the identification of the considerations for the operational feasibility determination of a four -lane to three-lane conversion. The results of the simulation analyses primarily confirmed the case study impacts. The CORSIM results indicated only a slight decrease in average arterial speed for through vehicles can be expected for a large range of peak-hour volumes, access densities, and access-point left-turn volumes (given the assumptions and design of the corridor case study evaluated). Typically, the reduction in the simulated average arterial speed (which includes both segment and signal delay) was between zero and four miles per hour when a roadway was converted from a four-lane undivided to a three-lane cross section. The simulated arterial level of service for a converted roadway, however, showed a decrease when the bi-directional peak-hour volume was about 1,750 vehicles per hour (or 17,500 vehicles per day if 10 percent of the daily volume is assumed to occur in the peak hour). Past research by others, however, indicates that 12,000 vehicles per day may be the operational capacity (i.e., level of service E) of a three-lane roadway due to vehicle platooning. The simulation results, along with past research and case study results, appear to support following volume-related feasibility suggestions for four-lane undivided to three-lane cross section conversions. It is recommended that a four-lane undivided to three-lane conversion be considered as a feasible (with respect to volume only) option when bi-directional peak-hour volumes are less than 1,500 vehicles per hour, but that some caution begin to be exercised when the roadway has a bi-directional peak-hour volume between 1,500 and 1,750 vehicles per hour. At and above 1,750 vehicles per hour, the simulation indicated a reduction in arterial level of service. Therefore, at least in Iowa, the feasibility of a four-lane undivided to three-lane conversion should be questioned and/or considered much more closely when a roadway has (or is expected to have) a peak-hour volume of more than 1,750 vehicles. Assuming that 10 percent of the daily traffic occurs during the peak-hour, these volume recommendations would correspond to 15,000 and 17,500 vehicles per day, respectively. These suggestions, however, are based on the results from one idealized case xi study corridor analysis. Individual operational analysis and/or simulations should be completed in detail once a four-lane undivided to three-lane cross section conversion is considered feasible (based on the general suggestions above) for a particular corridor. All of the simulations completed as part of this project also incorporated the optimization of signal timing to minimize vehicle delay along the corridor. A number of determination feasibility factors were identified from a review of the past research, before-and-after case study results, and the simulation sensitivity analysis. The existing and expected (i.e., design period) statuses of these factors are described and should be considered. The characteristics of these factors should be compared to each other, the impacts of other potentially feasible cross section improvements, and the goals/objectives of the community. The factors discussed in these guidelines include • roadway function and environment • overall traffic volume and level of service • turning volumes and patterns • frequent-stop and slow-moving vehicles • weaving, speed, and queues • crash type and patterns • pedestrian and bike activity • right-of-way availability, cost, and acquisition impacts • general characteristics, including - parallel roadways - offset minor street intersections - parallel parking - corner radii - at-grade railroad crossings xii The characteristics of these factors are documented in these guidelines, and their relationship to four-lane undivided to three-lane cross section conversion feasibility identified. This information is summarized along with some evaluative questions in this executive summary and Appendix C. In summary, the results of past research, numerous case studies, and the simulation analyses done as part of this project support the conclusion that in certain circumstances a four-lane undivided to three-lane conversion can be a feasible alternative for the mitigation of operational and/or safety concerns. This feasibility, however, must be determined by an evaluation of the factors identified in these guidelines (along with any others that may be relevant for a individual corridor). The expected benefits, costs, and overall impacts of a four-lane undivided to three-lane conversion should then be compared to the impacts of other feasible alternatives (e.g., adding a raised median) at a particular location.

Three theories of liberalism for the three theories of federalism. A Hegelian turn

This paper links different political liberal theories, considered from the perspective of their moral ontology, with federal democracies. After giving a brief description of these theories, I discuss their relationship with the theoretical and institutional models of federalism. As methodological tools, the paper introduces some Hegel’s political concepts and deals with their potential application to the analysis of federalism, taken into account the case of minorities in multinational democracies. I postulate the need for a moral and institutional refinement of liberal-democratic patterns that is better able to accommodate national pluralism than has so far been achieved by traditional constitutionalism.

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.

Like Man, Like Woman: Roman Women, Gender Qualities and Conjugal Relationships at the Turn of the First Century

Modern scholarship often discusses Roman women in terms of their difference from their male counterparts, frequently defining them as 'other'. This book shows how Roman male writers at the turn of the first century actually described women as not so different from men: the same qualities and abilities pertaining to the domains of parenthood, intellect and morals are ascribed by writers to women as well as to men. There are two voices, however: a traditional, ideal voice and an individual, realistic voice. This creates a duality of representations of women, which recurs across literary genres and reflects a duality of mentality. How can we interpret the paradoxical information about Roman women given by the male-authored texts? How does this duality of mentality inform us about gender roles and gender hierarchy? This work analyses well-known, as well as overlooked, passages from the writings of Pliny the Younger, Tacitus, Suetonius, Quintilian, Statius, Martial and Juvenal and sheds new light on Roman views of women and their abilities, on the notions of private and public and on conjugal relationships. In the process, the famous sixth satire of Juvenal is revisited and its topic reassessed, providing further insights into the complex issues of gender roles, marriage and emotions. By contrasting representations of women across a broad spectrum of literary genres, this book provides consistent findings that have wide significance for the study of Latin literature and the social history of the late first and early second centuries.