478 research outputs found

    Detection of antibody-dependent complement mediated inactivation of both autologous and heterologous virus in primary HIV-1 infection

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    Specific CD8 T-cell responses to human immunodeficiency virus type 1 (HIV-1) are induced in primary infection and make an important contribution to the control of early viral replication. The importance of neutralizing antibodies in containing primary viremia is questioned because they usually arise much later. Nevertheless antienvelope antibodies develop simultaneously with, or even before, peak viremia. We determined whether such antibodies might control viremia by complement-mediated inactivation (CMI). In each of seven patients studied, antibodies capable of CMI appeared at or shortly after the peak in viremia, concomitantly with detection of virus-specific T-cell responses. The CMI was effective on both autologous and heterologous HIV-1 isolates. Activation of the classical pathway and direct viral lysis were at least partly responsible. Since immunoglobulin G (IgG)-antibodies triggered the CMI, specific memory B cells could also be induced by vaccination. Thus, consideration should be given to vaccination strategies that induce IgG antibodies capable of CMI

    Combinatorial quorum sensing allows bacteria to resolve their social and physical environment

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    Quorum sensing (QS) is a cell–cell communication system that controls gene expression in many bacterial species, mediated by diffusible signal molecules. Although the intracellular regulatory mechanisms of QS are often well-understood, the functional roles of QS remain controversial. In particular, the use of multiple signals by many bacterial species poses a serious challenge to current functional theories. Here, we address this challenge by showing that bacteria can use multiple QS signals to infer both their social (density) and physical (mass-transfer) environment. Analytical and evolutionary simulation models show that the detection of, and response to, complex social/physical contrasts requires multiple signals with distinct half-lives and combinatorial (nonadditive) responses to signal concentrations. We test these predictions using the opportunistic pathogen Pseudomonas aeruginosa and demonstrate significant differences in signal decay betweeallyn its two primary signal molecules, as well as diverse combinatorial responses to dual-signal inputs. QS is associated with the control of secreted factors, and we show that secretome genes are preferentially controlled by synergistic “AND-gate” responses to multiple signal inputs, ensuring the effective expression of secreted factors in high-density and low mass-transfer environments. Our results support a new functional hypothesis for the use of multiple signals and, more generally, show that bacteria are capable of combinatorial communication

    Pricing and Conservation of Irrigation Water in Texas and New Mexico

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    Two possible policy alternatives for management of limited water supplies in arid portions of Texas and New Mexico were analyzed for economic feasibility. Detailed studies of the potential impact of a water accumulation policy for each of two irrigation districts (El Paso County Water Improvement District No. 1 in Texas, and the Elephant Butte Irrigation District in New Mexico) were undertaken using temporal linear programming techniques. Current cropping practices, soils, groundwater conditions, historical surface water allocations for Elephant Butte Reservoir and evaporation rates were incorporated within the analysis. Estimates of the benefits of accumulation of surplus portions of irrigation district member's annual surface water allocations, with subsequent use of the unevaporated portion in later years, were deemed insufficient to cover anticipated administrative costs of implementing the proposed policy. This suggests current allocations approximate a temporal optimum. Sensitivity analyses showed greater potential benefits, however, if current groundwater conditions worsen. Additional analysis of possible price-induced water conservation for the areas within the two states currently mining groundwater from the exhaustible Ogallala aquifer was also undertaken. The High Plains of Texas served as the representative region of study, with results assumed to be analogous for the portions of Eastern New Mexico relying on the Ogallala. Both static and temporal effects of a per unit tax on water pumpage and net returns were examined using a recursive linear programming model. Results indicated that imposition of a $20 per acre-foot tax on water pumped induced very little change in water use over a 40 year period, while reducing the present value of producer net returns from 9% to 27% depending upon initial groundwater conditions and the irrigation technology in use. These results imply that a price induced water conservation policy for the Ogallala is not economically justified

    Communitarian perspectives on social enterprise

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    Concepts of social enterprise have been debated repeatedly, and continue to cause confusion. In this paper, a meta-theoretical framework is developed through discussion of individualist and communitarian philosophy. Philosophers from both traditions build social theories that emphasise either consensus (a unitarist outlook) or diversity (a pluralist outlook). The various discourses in corporate governance reflect these assumptions and create four distinct approaches that impact on the relationship between capital and labour. In rejecting the traditional discourse of private enterprise, social enterprises have adopted other approaches to tackle social exclusion, each derived from different underlying beliefs about the purpose of enterprise and the nature of governance. The theoretical framework offers a way to understand the diversity found within the sector, including the newly constituted Community Interest Company (CIC).</p

    Collective sensing and collective responses in quorum-sensing bacteria

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    Bacteria often face fluctuating environments, and in response many species have evolved complex decision-making mechanisms to match their behaviour to the prevailing conditions. Some environmental cues provide direct and reliable information (such as nutrient concentrations) and can be responded to individually. Other environmental parameters are harder to infer and require a collective mechanism of sensing. In addition, some environmental challenges are best faced by a group of cells rather than an individual. In this review, we discuss how bacteria sense and overcome environmental challenges as a group using collective mechanisms of sensing, known as ‘quorum sensing’ (QS). QS is characterized by the release and detection of small molecules, potentially allowing individuals to infer environmental parameters such as density and mass transfer. While a great deal of the molecular mechanisms of QS have been described, there is still controversy over its functional role. We discuss what QS senses and how, what it controls and why, and how social dilemmas shape its evolution. Finally, there is a growing focus on the use of QS inhibitors as antibacterial chemotherapy. We discuss the claim that such a strategy could overcome the evolution of resistance. By linking existing theoretical approaches to data, we hope this review will spur greater collaboration between experimental and theoretical researchers

    Health Newscasts for Increasing Influenza Vaccination Coverage: An Inductive Reasoning Game Approach

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    Both pandemic and seasonal influenza are receiving more attention from mass media than ever before. Topics such as epidemic severity and vaccination are changing the way in which we perceive the utility of disease prevention. Voluntary influenza vaccination has been recently modeled using inductive reasoning games. It has thus been found that severe epidemics may occur because individuals do not vaccinate and, instead, attempt to benefit from the immunity of their peers. Such epidemics could be prevented by voluntary vaccination if incentives were offered. However, a key assumption has been that individuals make vaccination decisions based on whether there was an epidemic each influenza season; no other epidemiological information is available to them. In this work, we relax this assumption and investigate the consequences of making more informed vaccination decisions while no incentives are offered. We obtain three major results. First, individuals will not cooperate enough to constantly prevent influenza epidemics through voluntary vaccination no matter how much they learned about influenza epidemiology. Second, broadcasting epidemiological information richer than whether an epidemic occurred may stabilize the vaccination coverage and suppress severe influenza epidemics. Third, the stable vaccination coverage follows the trend of the perceived benefit of vaccination. However, increasing the amount of epidemiological information released to the public may either increase or decrease the perceived benefit of vaccination. We discuss three scenarios where individuals know, in addition to whether there was an epidemic, (i) the incidence, (ii) the vaccination coverage and (iii) both the incidence and the vaccination coverage, every influenza season. We show that broadcasting both the incidence and the vaccination coverage could yield either better or worse vaccination coverage than broadcasting each piece of information on its own

    Why Social Enterprises Are Asking to Be Multi-stakeholder and Deliberative: An Explanation around the Costs of Exclusion.

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    The study of multi-stakeholdership (and multi-stakeholder social enterprises in particular) is only at the start. Entrepreneurial choices which have emerged spontaneously, as well as the first legal frameworks approved in this direction, lack an adequate theoretical support. The debate itself is underdeveloped, as the existing understanding of organisations and their aims resist an inclusive, public interest view of enterprise. Our contribution aims at enriching the thin theoretical reflections on multi-stakeholdership, in a context where they are already established, i.e. that of social and personal services. The aim is to provide an economic justification on why the governance structure and decision-making praxis of the firm needs to account for multiple stakeholders. In particular with our analysis we want: a) to consider production and the role of firms in the context of the “public interest” which may or may not coincide with the non-profit objective; b) to ground the explanation of firm governance and processes upon the nature of production and the interconnections between demand and supply side; c) to explain that the costs associated with multi-stakeholder governance and deliberation in decision-making can increase internal efficiency and be “productive” since they lower internal costs and utilise resources that otherwise would go astray. The key insight of this work is that, differently from major interpretations, property costs should be compared with a more comprehensive range of costs, such as the social costs that emerge when the supply of social and personal services is insufficient or when the identification of aims and means is not shared amongst stakeholders. Our model highlights that when social costs derived from exclusion are high, even an enterprise with costly decisional processes, such as the multistakeholder, can be the most efficient solution amongst other possible alternatives
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