A Theory of Common Dealing with the Internet as an Innovative Distribution Channel

After the emergence of the Internet, an interesting question arises that what is its impact on the firms’ channel and pricing strategies. This paper applies game theory to study the strategic interactions between rational manufacturers, retailers, and consumers, and it generates the following results: 1. The presence of the Internet allows imperfectly competitive manufacturers to better coordinate their pricing, targeting, and channel strategies, thereby minimizing the agency costs involved in common dealing at the traditional outlets, which in turn enhances the manufacturers’ profits. 2. Exclusive dealing may and may not become more prevalent in the presence of the Internet. It all depends on the ratio of the population of switchers to the entire population of consumers. 3. The presence of the Internet allows a monopolistic manufacturer to screen consumers by serving different people at different outlets. Screening is less effective, however, in the case of imperfect competition. 4. A dynamic adjustment process is obtained which describes how a manufacturer should optimally change his channel and pricing strategies when the population of the Internet purchasers grows over time

A Theory of Common Dealing with the Internet as an Innovative Distribution Channel

After the emergence of the Internet, an interesting question arises that what is its impact on the firms’ channel and pricing strategies. This paper applies game theory to study the strategic interactions between rational manufacturers, retailers, and consumers, and it generates the following results: 1. The presence of the Internet allows imperfectly competitive manufacturers to better coordinate their pricing, targeting, and channel strategies, thereby minimizing the agency costs involved in common dealing at the traditional outlets, which in turn enhances the manufacturers’ profits. 2. Exclusive dealing may and may not become more prevalent in the presence of the Internet. It all depends on the ratio of the population of switchers to the entire population of consumers. 3. The presence of the Internet allows a monopolistic manufacturer to screen consumers by serving different people at different outlets. Screening is less effective, however, in the case of imperfect competition. 4. A dynamic adjustment process is obtained which describes how a manufacturer should optimally change his channel and pricing strategies when the population of the Internet purchasers grows over time

Screening Outside the Catalytic Site: Inhibition of Macromolecular Inter-actions Through Structure-Based Virtual Ligand Screening Experiments

During these last 15 years, drug discovery strategies have essentially focused on identifying small molecules able to inhibit catalytic sites. However, other mechanisms could be targeted. Protein-protein interactions play crucial roles in a number of biological processes, and, as such, their disruption or stabilization is becoming an area of intense activity. Along the same line, inhibition of protein-membrane could be of major importance in several disease indications. Despite the many challenges associated with the development of such classes of interaction modulators, there has been considerable success in the recent years. Importantly, through the existence of protein hot-spots and the presence of druggable pockets at the macromolecular interfaces or in their vicinities, it has been possible to find small molecule effectors using a variety of screening techniques, including combined virtual ligand-in vitro screening strategy. Indeed such in silico-in vitro protocols emerge as the method of choice to facilitate our quest of novel drug-like compounds or of mechanistic probes aiming at facilitating the understanding of molecular reactions involved in the Health and Disease process. In this review, we comment recent successes of combined in silico-in vitro screening methods applied to modulating macromolecular interactions with a special emphasis on protein-membrane interactions

Genetic interactions: the missing links for a better understanding of cancer susceptibility, progression and treatment

It is increasingly clear that complex networks of relationships between genes and/or proteins govern neoplastic processes. Our understanding of these networks is expanded by the use of functional genomic and proteomic approaches in addition to computational modeling. Concurrently, whole-genome association scans and mutational screens of cancer genomes identify novel cancer genes. Together, these analyses have vastly increased our knowledge of cancer, in terms of both "part lists" and their functional associations. However, genetic interactions have hitherto only been studied in depth in model organisms and remain largely unknown for human systems. Here, we discuss the importance and potential benefits of identifying genetic interactions at the human genome level for creating a better understanding of cancer susceptibility and progression and developing novel effective anticancer therapies. We examine gene expression profiles in the presence and absence of co-amplification of the 8q24 and 20q13 chromosomal regions in breast tumors to illustrate the molecular consequences and complexity of genetic interactions and their role in tumorigenesis. Finally, we highlight current strategies for targeting tumor dependencies and outline potential matrix screening designs for uncovering molecular vulnerabilities in cancer cells

Target identification strategies in plant chemical biology

The current needs to understand gene function in plant biology increasingly require more dynamic and conditional approaches opposed to classic genetic strategies. Gene redundancy and lethality can substantially complicate research, which might be solved by applying a chemical genetics approach. Now understood as the study of small molecules and their effect on biological systems with subsequent target identification, chemical genetics is a fast developing field with a strong history in pharmaceutical research and drug discovery. In plant biology however, chemical genetics is still largely in the starting blocks, with most studies relying on forward genetics and phenotypic analysis for target identification, whereas studies including direct target identification are limited. Here, we provide an overview of recent advances in chemical genetics in plant biology with a focus on target identification. Furthermore, we discuss different strategies for direct target identification and the possibilities and challenges for plant biology

Waging the War for Talent: Do Recruitment and Screening Strategies Raise Employee Performance?

We use data from the Multi-City Study of Urban Inequality to provide an empirical answer to the question, “Do recruitment and screening strategies raise employee performance?” Our approach differs from previous empirical work in that we allow for changes in screening behavior to accompany changes in recruitment behavior. In the end, our results are consistent with those of the previous literature that ignores the auxiliary effect of recruitment through screening, in that we find no effect of recruitment methods on worker performance

Iterative in Situ Click Chemistry Assembles a Branched Capture Agent and Allosteric Inhibitor for Akt1

We describe the use of iterative in situ click chemistry to design an Akt-specific branched peptide triligand that is a drop-in replacement for monoclonal antibodies in multiple biochemical assays. Each peptide module in the branched structure makes unique contributions to affinity and/or specificity resulting in a 200 nM affinity ligand that efficiently immunoprecipitates Akt from cancer cell lysates and labels Akt in fixed cells. Our use of a small molecule to preinhibit Akt prior to screening resulted in low micromolar inhibitory potency and an allosteric mode of inhibition, which is evidenced through a series of competitive enzyme kinetic assays. To demonstrate the efficiency and selectivity of the protein-templated in situ click reaction, we developed a novel QPCR-based methodology that enabled a quantitative assessment of its yield. These results point to the potential for iterative in situ click chemistry to generate potent, synthetically accessible antibody replacements with novel inhibitory properties

Design of Experiments for Screening

The aim of this paper is to review methods of designing screening experiments, ranging from designs originally developed for physical experiments to those especially tailored to experiments on numerical models. The strengths and weaknesses of the various designs for screening variables in numerical models are discussed. First, classes of factorial designs for experiments to estimate main effects and interactions through a linear statistical model are described, specifically regular and nonregular fractional factorial designs, supersaturated designs and systematic fractional replicate designs. Generic issues of aliasing, bias and cancellation of factorial effects are discussed. Second, group screening experiments are considered including factorial group screening and sequential bifurcation. Third, random sampling plans are discussed including Latin hypercube sampling and sampling plans to estimate elementary effects. Fourth, a variety of modelling methods commonly employed with screening designs are briefly described. Finally, a novel study demonstrates six screening methods on two frequently-used exemplars, and their performances are compared

Identification of novel 2-benzoxazolinone derivatives with specific inhibitory activity against the HIV-1 nucleocapsid protein

In this report, we present a new benzoxazole derivative endowed with inhibitory activity against the HIV-1 nucleocapsid protein (NC). NC is a 55-residue basic protein with nucleic acid chaperone properties, which has emerged as a novel and potential pharmacological target against HIV-1. In the pursuit of novel NC-inhibitor chemotypes, we performed virtual screening and in vitro biological evaluation of a large library of chemical entities. We found that compounds sharing a benzoxazolinone moiety displayed putative inhibitory properties, which we further investigated by considering a series of chemical analogues. This approach provided valuable information on the structure-activity relationships of these compounds and, in the process, demonstrated that their anti-NC activity could be finely tuned by the addition of specific substituents to the initial benzoxazolinone scaffold. This study represents the starting point for the possible development of a new class of antiretroviral agents targeting the HIV-1 NC protein