"Call for prices": Strategic implications of raising consumers' costs

Many consumer durable retailers often do not advertise their prices and instead ask consumers to call them for prices. It is easy to see that this practice increases the consumers' cost of learning the prices of products they are considering, yet firms commonly use such practices. Not advertising prices may reduce the firm's advertising costs, but the strategic effects of doing so are not clear. Our objective is to examine the strategic effects of this practice. In particular, how does making price discovery more difficult for consumers affect competing retailers' price, service decisions, and profits? We develop a model in which a manufacturer sells its product through a high-service retailer and a low-service retailer. Consumers can purchase the retail service at the high-end retailer and purchase the product at the competing low-end retailer. Therefore, the high-end retailer faces a free-riding problem. A retailer first chooses its optimal service levels. Then, it chooses its optimal price levels. Finally, a retailer decides whether to advertise its prices. The model results in four structures: (1) both retailers advertise prices, (2) only the low-service retailer advertises price, (3) only the high-service retailer advertises price, and (4) neither retailer advertises price. We find that when a retailer does not advertise its price and makes price discovery more difficult for consumers, the competition between the retailers is less intense. However, the retailer is forced to charge a lower price. In addition, if the competing retailer does advertise its prices, then the competing retailer enjoys higher profit margins. We identify conditions under which each of the above four structures is an equilibrium and show that a low-service retailer not advertising its price is a more likely outcome than a high-service retailer doing so. We then solve the manufacturer's problem and find that there are several instances when a retailer's advertising decisions are different from what the manufacturer would want. We describe the nature of this channel coordination problem and identify some solutions. © 2010 INFORMS.

Immunization with cocktail of HIV-derived peptides in montanide ISA-51 is immunogenic, but causes sterile abscesses and unacceptable reactogenicity.

BACKGROUND: A peptide vaccine was produced containing B and T cell epitopes from the V3 and C4 Envelope domains of 4 subtype B HIV-1 isolates (MN, RF, CanO, & Ev91). The peptide mixture was formulated as an emulsion in incomplete Freund's adjuvant (IFA). METHODS: Low-risk, healthy adult subjects were enrolled in a randomized, placebo-controlled dose-escalation study, and selected using criteria specifying that 50% in each study group would be HLA-B7+. Immunizations were scheduled at 0, 1, and 6 months using a total peptide dose of 1 or 4 mg. Adaptive immune responses in16 vaccine recipients and two placebo recipients after the 2nd immunization were evaluated using neutralization assays of sera, as well as ELISpot and ICS assays of cryopreserved PBMCs to assess CD4 and CD8 T-cell responses. In addition, (51)Cr release assays were performed on fresh PBMCs following 14-day stimulation with individual vaccine peptide antigens. RESULTS: 24 subjects were enrolled; 18 completed 2 injections. The study was prematurely terminated because 4 vaccinees developed prolonged pain and sterile abscess formation at the injection site-2 after dose 1, and 2 after dose 2. Two other subjects experienced severe systemic reactions consisting of headache, chills, nausea, and myalgia. Both reactions occurred after the second 4 mg dose. The immunogenicity assessments showed that 6/8 vaccinees at each dose level had detectable MN-specific neutralizing (NT) activity, and 2/7 HLA-B7+ vaccinees had classical CD8 CTL activity detected. However, using both ELISpot and ICS, 8/16 vaccinees (5/7 HLA-B7+) and 0/2 controls had detectable vaccine-specific CD8 T-cell responses. Subjects with moderate or severe systemic or local reactions tended to have more frequent T cell responses and higher antibody responses than those with mild or no reactions. CONCLUSIONS: The severity of local responses related to the formulation of these four peptides in IFA is clinically unacceptable for continued development. Both HIV-specific antibody and T cell responses were induced and the magnitude of response correlated with the severity of local and systemic reactions. If potent adjuvants are necessary for subunit vaccines to induce broad and durable immune responses, careful, incremental clinical evaluation is warranted to minimize the risk of adverse events. TRIAL REGISTRATION: ClinicalTrials.gov NCT00000886.

Mechanisms of CD8+ T Cell Mediated Virus Inhibition in HIV-1 Virus Controllers

CD8+ T cells are associated with long term control of virus replication to low or undetectable levels in a population of HIV+ therapy-naïve individuals known as virus controllers (VCs; <5000 RNA copies/ml and CD4+ lymphocyte counts >400 cells/µl). These subjects' ability to control viremia in the absence of therapy makes them the gold standard for the type of CD8+ T-cell response that should be induced with a vaccine. Studying the regulation of CD8+ T cells responses in these VCs provides the opportunity to discover mechanisms of durable control of HIV-1. Previous research has shown that the CD8+ T cell population in VCs is heterogeneous in its ability to inhibit virus replication and distinct T cells are responsible for virus inhibition. Further defining both the functional properties and regulation of the specific features of the select CD8+ T cells responsible for potent control of viremia the in VCs would enable better evaluation of T cell-directed vaccine strategies and may inform the design of new therapies.

Here we discuss the progress made in elucidating the features and regulation of CD8+ T cell response in virus controllers. We first detail the development of assays to quantify CD8+ T cells' ability to inhibit virus replication. This includes the use of a multi-clade HIV-1 panel which can subsequently be used as a tool for evaluation of T cell directed vaccines. We used these assays to evaluate the CD8+ response among cohorts of HIV-1 seronegative, HIV-1 acutely infected, and HIV-1 chronically infected (both VC and chronic viremic) patients. Contact and soluble CD8+ T cell virus inhibition assays (VIAs) are able to distinguish these patient groups based on the presence and magnitude of the responses. When employed in conjunction with peptide stimulation, the soluble assay reveals peptide stimulation induces CD8+ T cell responses with a prevalence of Gag p24 and Nef specificity among the virus controllers tested. Given this prevalence, we aimed to determine the gene expression profile of Gag p24-, Nef-, and unstimulated CD8+ T cells. RNA was isolated from CD8+ T-cells from two virus controllers with strong virus inhibition and one seronegative donor after a 5.5 hour stimulation period then analyzed using the Illumina Human BeadChip platform (Duke Center for Human Genome Variation). Analysis revealed that 565 (242 Nef and 323 Gag) genes were differentially expressed in CD8+ T-cells that were able to inhibit virus replication compared to those that could not. We compared the differentially expressed genes to published data sets from other CD8+ T-cell effector function experiments focusing our analysis on the most recurring genes with immunological, gene regulatory, apoptotic or unknown functions. The most commonly identified gene in these studies was TNFRSF9. Using PCR in a larger cohort of virus controllers we confirmed the up-regulation of TNFRSF9 in Gag p24 and Nef-specific CD8+ T cell mediated virus inhibition. We also observed increase in the mRNA encoding antiviral cytokines macrophage inflammatory proteins (MIP-1α, MIP-1αP, MIP-1β), interferon gamma (IFN-γ), granulocyte-macrophage colony-stimulating factor (GM-CSF), and recently identified lymphotactin (XCL1).

Our previous work suggests the CD8+ T-cell response to HIV-1 can be regulated at the level of gene regulation. Because RNA abundance is modulated by transcription of new mRNAs and decay of new and existing RNA we aimed to evaluate the net rate of transcription and mRNA decay for the cytokines we identified as differentially regulated. To estimate rate of mRNA synthesis and decay, we stimulated isolated CD8+ T-cells with Gag p24 and Nef peptides adding 4-thiouridine (4SU) during the final hour of stimulation, allowing for separation of RNA made during the final hour of stimulation. Subsequent PCR of RNA isolated from these cells, allowed us to determine how much mRNA was made for our genes of interest during the final hour which we used to calculate rate of transcription. To assess if stimulation caused a change in RNA stability, we calculated the decay rates of these mRNA over time. In Gag p24 and Nef stimulated T cells , the abundance of the mRNA of many of the cytokines examined was dependent on changes in both transcription and mRNA decay with evidence for potential differences in the regulation of mRNA between Nef and Gag specific CD8+ T cells. The results were highly reproducible in that in one subject that was measured in three independent experiments the results were concordant.

This data suggests that mRNA stability, in addition to transcription, is key in regulating the direct anti-HIV-1 function of antigen-specific memory CD8+ T cells by enabling rapid recall of anti-HIV-1 effector functions, namely the production and increased stability of antiviral cytokines. We have started to uncover the mechanisms employed by CD8+ T cell subsets with antigen-specific anti-HIV-1 activity, in turn, enhancing our ability to inhibit virus replication by informing both cure strategies and HIV-1 vaccine designs that aim to reduce transmission and can aid in blocking HIV-1 acquisition.

Partners moving freely

Examines the provisions of European Parliament and Council Directive 2004/38 protecting the rights of EU citizens' partners to move freely within the EU. Highlights criticisms of the previous legislation, in particular, the lack of rights for cohabitees. Considers the extension of rights to registered partners, and the improved position of unmarried partners, noting, however, the lack of guidance on whether an unmarried couple's relationship is "durable" and "duly attested". Explains the circumstances in which non-EU spouses will not now lose the right of residence on divorce. [From Legal Journals Index]

The use of mineral trioxide aggregate in endodontics - status report

Mineral trioxide aggregate (MTA) is a clinical product comprising a mixture of Portland cement and bismuth oxide which is currently used as a root−filling material in dentistry. It has good biological compatibility, is capable of promoting both osteogenesis and cementogensis, and is finding increasing use in endodontic therapy. It is dimensionally stable, and provides an acceptable and durable seal for endodontically treated teeth. This article reviews the chemistry and applications of MTA, and highlights the fact that very little is currently known about the hydration chemistry, phase evolution and stability of this cement in physiological environments. However, biological effects of MTA have been well documented and are considered in detail. The article concludes that this material is a useful addition to the range of materials available for clinical application in endodontics.

Marginal adaptation and performance of bioactive dental restorative materials in deciduous and young permanent teeth

Objective: The aim of this study was to investigate the adaptation of different types of restorations towards deciduous and young permanent teeth. Materials and Methods: Class V cavities were prepared in deciduous and young permanent teeth and filled with different materials (a conventional glass-ionomer, a resin-modified glass-ionomer, a poly-acid-modified composite resin and a conventional composite resin). Specimens were aged in artificial saliva for 1, 6, 12 and 18 months, then examined by SEM. Results: The composite resin and the polyacid-modified composite had better marginal adaptation than the glass-ionomers,though microcracks developed in the enamel of the tooth. The glass-ionomers showed inferior marginal quality and durability, but no microcracking of the enamel. The margins of the resin-modified glass-ionomer were slightly superior to the conventional glass-ionomer. Conditioning improved the adaptation of the composite resin, but the type of tooth made little or no difference to the performance of the restorative material. All materials were associated with the formation of crystals in the gaps between the filling and the tooth; the quantity and shape of these crystals varied with the material. Conclusions: Resin-based materials are generally better at forming sound, durable margins in deciduous and young permanent teeth than cements, but are associated with microcracks in the enamel. All fluoride-releasing materials give rise to crystalline deposits.

Intertwined ocean and climate: implications for international climate negotiations

The atmosphere and ocean are two components of the Earth system that are essential for life, yet humankind is altering both. Contemporary climate change is now a well-identified problem: anthropogenic causes, disturbance in extreme events patterns, gradual environmental changes, widespread impacts on life and natural resources, and multiple threats to human societies all around the world. But part of the problem remains largely unknown outside the scientific community: significant changes are also occurring in the ocean, threatening life and its sustainability on Earth. This Policy Brief explains the significance of these changes in the ocean. It is based on a scientific paper recently published in Science (Gattuso et al., 2015), which synthesizes recent and future changes to the ocean and its ecosystems, as well as to the goods and services they provide to humans. Two contrasting CO2 emission scenarios are considered: the high emissions scenario (also known as “business-as-usual” and as the Representative Concentration Pathway 8.5, RCP8.5) and a stringent emissions scenario (RCP2.6) consistent with the Copenhagen Accord1 of keeping mean global temperature increase below 2°C in 2100.

Paisajes para el Medioambiente. Estudio de caso.

Una de las cuencas hidrográficas más importante de la Península es la del río Tajo, por su extensión y por su caudal. Se trata de una fosa tectónica calificable de modélica. Dos moles montañosas, el Sistema central y los Montes de Toledo en sentido amplio, la flanquean al Norte y al Sur. La dovela hundida, formada por idénticos materiales que las Sierras, granitos y gneis, alcanza una gran profundidad. Al Este el Sistema Ibérico castellano, principalmente calizo y mesozoico, cierra Castilla y la cuenca, viniendo a dar vida con el agua de sus nieves a un Tajo niño’. El inicio de su Historia Geológica podemos situarlo en el Paleozoico, tiempo geológico durante el cual los territorios donde hoy se sitúa la Meseta estaban formando grandes cordilleras producto de la Orogenia Herciniana. La última etapa de la formación de los relieves actuales de la cuenca la encontramos en la reactivación de los antiguos macizos arrasados. Se inicia con los materiales de la raña y sus equivalentes en el centro de la Cuenca o Fosa del Tajo, y se caracteriza por una progresiva individualización de los procesos, pasándose de las grandes superficies generalizadas en macizos y cuencas, Sierras y Fosa del Tajo, a las pequeñas llanuras en franja u orla, que quedan localizadas en cada cuenca fluvial a medida que éstas se van consolidando por jerarquización, y partir de un río generatriz o emisario principal, el Tajo. La tectónica, procesos posteriores de captura, reajustes climáticos..., no permiten aún determinar cuál fue el orden de jerarquía en los ríos que hoy conocemos; no obstante, puede aventurarse que Jarama-Henares, Perales-Alberche y Guadarrama serían los primeros y Manzanares, Guadalix, Tajuña, los siguientes, y así sucesivamente. La síntesis de la realidad geológica, litológica y climática va a coadyuvar, frenando o favoreciendo, el desarrollo y la diferenciación entre los paisajes vegetales de las zonas montañosas y los de las depresiones terciarias y penillanuras paleozoicas, en un territorio marcado por el predominio del clima mediterráneo continentalizado, con matices de montaña y áreas de influencia atlántica.

Arching action in high strength concrete slabs

The corrosion of reinforcement in bridge deck slabs has been the cause of major deterioration and high costs in repair and maintenance.This problem could be overcome by reducing the amount of reinforcement and/or altering the location.This is possible because, in addition to the strength provided by the reinforcement, bridge deck slabs have an inherent strength due to the in-plane arching forces set up as a result of restraint provided by the slab boundary conditions. This is known as arching action or Compressive Membrane Action (CMA). It has been recognised for some time that laterally restrained slabs exhibit strengths far in excess of those predicted by most design codes but the phenomenon has not been recognised by the majority of bridge design engineers. This paper presents the results of laboratory tests on fifteen reinforced concrete slab strips typical of a bridge deck slab and compares them to predicted strengths using the current codes and CMA theory. The tests showed that the strength of laterally restrained slabs is sensitive to both the degree of external lateral restraint and the concrete compressive strength.The tests particularly highlighted the benefits in strength obtained from very high strength concrete slabs. The theory extends the existing knowledge of CMA in slabs with concrete compressive strengths up to 100 N/mm[2] and promotes more economical and durable bridge deck construction by utilising the benefits of high strength concrete.

Agricultura urbana, condición para el desarrollo sostenible y la mejora del paisaje

Este artículo resulta de investigaciones en torno al “enverdecimiento” de las ciudades y las oportunidades de la agricultura urbana para la alimentación de una población en constante aumento que no trabaja la tierra. También es fruto de actividades de mejora de ambientes urbanos realizadas con la Escuela de Ingenieros Agrónomos de la Universidad Politécnica de Madrid. A través de casos de agricultura urbana, entendiendo por ella el conjunto de prácticas para la producción de alimentos y plantas ornamentales dentro de las ciudades y en sus entornos, se analizan alternativas para la recuperación de espacios construidos e incremento de la calidad de vida de la población. Todo ello se traduce, además, en creación de riqueza y mejora del paisaje urbano, siempre desde criterios de sostenibilidad que favorecen el desarrollo local desde la Cumbre de la Tierra de Río de 1992 y la Conferencia sobre Desarrollo Sostenible Río+20 de 2013.

Experimental Design to Optimize High-Volume Ash Grout in the Presence of Welan Gum and Superplasticizer

Applications such as soil, rock and oil-well grouting all require enormous amounts of cement and are good examples of areas where a high volume of fly ash could partially replace cement to produce low-cost, environmentally safe and durable concrete. There is an increasing need to identify the rheological properties of cement grout using a simple test to determine the fluidity, and other properties of underwater grouts such as washout resistance and compressive strength. This paper presents statistical models developed using a fractorial design which was carried out to model the influence of key parameters on properties affecting the performance of underwater grout. Such responses of fluidity included mini-slump and flow time measured by Marsh cone, washout resistance, unit weight and compressive strength. The models are valid for mixes with 0.40 to 0.60 water-to-cementitious materials ratio, 0.02 to 0.08% of anti-washout admixture, by mass of binder, and 0.6 to 1.8% of superplasticizer, by mass of cementitious materials. The grout was made with 50% of pulverized-fuel ash replacement, by mass ofcementitious materials. Also presented are the derived models that enable the identification of underlying primary factors and their interactions that influence the modelled responses of underwater cement grout. Such parameters can be useful to reduce the test protocol needed for proportioning of underwater cement grout. This paper highlighted the influence of W/CM and dosage of antiwashout admixture and superplasticizer on fluidity, washout resistance and compressive strength and attempted also to demonstrate the usefulness of the models to improve understanding of trade-offs between parameters.

Strength and permeation properties as an indicator of durability of concrete

Durability of concrete is a great concern to all designers, owners and users of reinforced concrete structures. As a result, more restrictive regulations are being introduced in various Codes of Practice dealing with the design of these structures. Attempts are being made by various researchers to develop performance based specification. For this to be successful standard non destructive tests are required which will be used to assess the durability of concretes. In parallel with this approach, a research team in Queen’s University Belfast, U. K., investigated the effect of different mix parameters on workability, strength and various permeation properties. Furthermore, durability parameters such as freeze-thaw salt scaling resistance and carbonation depth were also investigated. The research was part funded by the Department of Environment, Transport and the Regions (DETR). This paper reports of the findings from this study. The results from this investigation showed that some of the non destructive tests used were reasonably well correlated with carbonation and freeze-thaw salt scaling resistance of CEM I concrete. If the mix parameters such as aggregate-cement ratio or water-cement ratio are known, better correlation can be obtained. Further investigation is required varying other mix parameters including various aggregates, admixtures and air entrainments before the result can be used for developing mix design methods for durable concretes. Also long term site tests are required to validate the results obtained from the accelerated laboratory tests used to study the carbonation resistance and freeze-thaw salt scaling resistance.

Rapid construction of arch bridges using the innovative FlexiArch

Masonry arches are strong, durable, aesthetically pleasing and largely maintenance free, yet since 1900 there has been a dramatic decline in their use. However, designers, contractors and clients now have access to a new method of constructing arches incorporating precast concrete voussoirs interconnected via polymeric reinforcement and a concrete screed. No centring is necessary, as the FlexiArch, when it is lifted, transforms under the forces of gravity into the desired arch shape. After discussing general aspects of innovation, the basic concept of the arch bridge system is presented along with technological advances since it was patented. Experiences gained from building over 40 FlexiArch bridges in the UK and Ireland and from model and full-scale tests carried out to validate the system during installation and in service are described. Thus under load the system behaves like a traditional masonry arch and existing analysis methods can be used for design and assessment.

The anonymity of the hunt: A critique of hunting as sharing

Hunter-gatherers are often ascribed a “monistic” worldview at odds with the nature-society dichotomy. The centerpiece of this claim is that they view hunting as similar to sharing within the band and prey animals as part of a common sphere of sociality. This article challenges this thesis. An examination of the work of its main proponents shows that it conflates two different senses of “animal”—the flesh-and-blood animals of the hunt and the animal Spirit that is said to control the animals. The sharing motif in hunting makes sense with respect to the anthropomorphic Spirit but not to the animals hunted. The conditions of the hunt as a spatiotemporal event provide further grounds for skepticism toward the idea of hunting-as-sharing. Drawing on biologist Robert Hinde’s model of relationships, I argue that hunting represents an anonymous one-off interaction that cannot develop into a personal relationship, in stark contrast to the durable forms of personalized sociality associated with the hunter-gatherer band. This is not to deny the possibility of human-animal cosociality in the form of personal relationships but rather to redirect the search away from the hunt to the interface with domesticated animals.