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Product Recommendation Strategy and Seller-Biased Recommendations We now segue from bundling economics to the theory of strategic product recommendation, and the nuances that arise when a product or service provider rethinks its approach about how to push a more profitable product to consumers, who exhibit heterogeneity with respect to their fit with it. The optimal strategy depends both on the search cost faced by consumers as well as the accuracy of information the seller possesses about consumer preferences. Using a recommendation system, for example, a seller can nudge potential consumers to a high-margin product, instead of simply recommending the product that would have offered them the highest utility [[28]]. In a two-channel scenario, a larger bundle discount entices more consumers to buy both channels but also results in a higher lost revenue as consumers who would have purchased both in any case can now do so at a lower price. [Extracted from the article]

We characterized the acute B cell response in adults with cholera by analyzing the repertoire, specificity, and functional characteristics of 138 monoclonal antibodies (MAbs) generated from single-cell-sorted plasmablasts. We found that the cholera-induced responses were characterized by high levels of somatic hypermutation and large clonal expansions. A majority of the expansions targeted cholera toxin (CT) or lipopolysaccharide (LPS). Using a novel proteomics approach, we were able to identify sialidase as another major antigen targeted by the antibody response to Vibrio cholerae infection. Antitoxin MAbs targeted both the A and B subunits, and most were also potent neutralizers of enterotoxigenic Escherichia coli heat-labile toxin. LPS-specific MAbs uniformly targeted the O-specific polysaccharide, with no detectable responses to either the core or the lipid moiety of LPS. Interestingly, the LPS-specific antibodies varied widely in serotype specificity and functional characteristics. One participant infected with the Ogawa serotype produced highly mutated LPS-specific antibodies that preferentially bound the previously circulating Inaba serotype. This demonstrates durable memory against a polysaccharide antigen presented at the mucosal surface and provides a mechanism for the long-term, partial heterotypic immunity seen following cholera.ImportanceCholera is a diarrheal disease that results in significant mortality. While oral cholera vaccines are beneficial, they do not achieve equivalent protection compared to infection with Vibrio cholerae Although antibodies likely mediate protection, the mechanisms of immunity following cholera are poorly understood, and a detailed understanding of antibody responses to cholera is of significance for human health. In this study, we characterized the human response to cholera at the single-plasmablast, monoclonal antibody level. Although this approach has not been widely applied to the study of human bacterial infection, we were able to uncover the basis of cross-reactivity between different V. cholerae serotypes and the likely impact of prior enterotoxigenic Escherichia coli exposure on the response to cholera, as well as identify novel antigenic targets. In addition to improving our understanding of the repertoire and function of the antibody response to cholera in humans, this study has implications for future cholera vaccination efforts.

The second article in this Special Section reflects the actions of not one AI firm, but instead 1,387 publicly-traded companies in the People's Republic of China from 2007 to 2018. An interesting, empirically testable implication of the authors' theoretical analysis is whether different enforcement regimes, which result in differences of piracy cost, do result in the nuanced prevalence (or not) of product bundles on the local markets for information goods as it would be predicted by the model. The authors report that they found evidence for a causal link in the presence of higher-intensity AI investments proxied by the estimated AI applications of individual firms with their overall employment as well as higher employment of nonacademically-trained workers. The authors' results are developed as a function of product similarity (amounting to a valuation discount factor between 0 and 1) and (expected per-product) piracy cost, which provides a somewhat new perspective, as the set of parameters where bundling dominates becomes nonconvex - due to the newly discovered "wedge" of intermediate piracy costs and sufficiently high product similarity. [Extracted from the article]

Using an established nonhuman primate model, rhesus macaques were infected intravenously with a chimeric simian immunodeficiency virus (SIV) consisting of SIVmac239 with the human immunodeficiency virus type 1 (HIV-1) reverse transcriptase from clone HXBc2 (RT-SHIV). The impacts of two enhanced (four- and five-drug) highly active antiretroviral therapies (HAART) on early viral decay and rebound were determined. The four-drug combination consisted of an integrase inhibitor, L-870-812 (L-812), together with a three-drug regimen comprising emtricitabine [(-)-FTC], tenofovir (TFV), and efavirenz (EFV). The five-drug combination consisted of one analog for each of the four DNA precursors {using TFV, (-)-FTC, (-)-β-D-(2R,4R)-1,3-dioxolane-2,6-diaminopurine (amdoxovir [DAPD]), and zidovudine (AZT)}, together with EFV. A cohort treated with a three-drug combination of (-)-FTC, TFV, and EFV served as treated controls. Daily administration of a three-, four-, or five-drug combination of antiretroviral agents was initiated at week 6 or 8 after inoculation and continued up to week 50, followed by a rebound period. Plasma samples were collected routinely, and drug levels were monitored using liquid chromatography-tandem mass spectrometry (LC-MS-MS). Viral loads were monitored with a standard TaqMan quantitative reverse transcriptase PCR (qRT-PCR) assay. Comprehensive analyses of replication dynamics were performed. RT-SHIV infection in rhesus macaques produced typical viral infection kinetics, with untreated controls establishing persistent viral loads of >10(4) copies of RNA/ml. RT-SHIV loads at the start of treatment (V0) were similar in all treated cohorts (P > 0.5). All antiretroviral drug levels were measureable in plasma. The four-drug and five-drug combination regimens (enhanced HAART) improved suppression of the viral load (within 1 week; P < 0.01) and had overall greater potency (P < 0.02) than the three-drug regimen (HAART). Moreover, rebound viremia occurred rapidly following cessation of any treatment. The enhanced HAART (four- or five-drug combination) showed significant improvement in viral suppression compared to the three-drug combination, but no combination was sufficient to eliminate viral reservoirs.

RT-SHIV is a chimera of simian immunodeficiency virus (SIV) containing the reverse transcriptase (RT)-encoding region of human immunodeficiency virus type 1 (HIV-1) within the backbone of SIVmac239. It has been used in a non-human primate model for studies of non-nucleoside RT inhibitors (NNRTI) and highly active antiretroviral therapy (HAART). We and others have identified several mutations that arise in the "foreign" HIV-1 RT of RT-SHIV during in vivo replication. In this study we catalogued amino acid substitutions in the HIV-1 RT and in regions of the SIV backbone with which RT interacts that emerged 30 weeks post-infection from seven RT-SHIV-infected rhesus macaques. The virus set points varied from relatively high virus load, moderate virus load, to undetectable virus load. The G196R substitution in RT was detected from 6 of 7 animals at week 4 post-infection and remained in virus from 4 of 6 animals at week 30. Virus from four high virus load animals showed several common mutations within RT, including L74V or V75L, G196R, L214F, and K275R. The foreign RT from high virus load isolates exhibited as much variation as that of the highly variable envelope surface glycoprotein, and 10-fold higher than that of the native RT of SIVmac239. Isolates from moderate virus load animals showed much less variation in the foreign RT than the high virus load isolates. No variation was found in SIVmac239 genes known to interact with RT. Our results demonstrate substantial adaptation of the foreign HIV-1 RT in RT-SHIV-infected macaques, which most likely reflects selective pressure upon the foreign RT to attain optimal activity within the context of the chimeric RT-SHIV and the rhesus macaque host.

Highly active antiretroviral therapy (HAART) can reduce levels of human immunodeficiency virus type 1 (HIV-1) to undetectable levels in infected individuals, but the virus is not eradicated. The mechanisms of viral persistence during HAART are poorly defined, but some reservoirs have been identified, such as latently infected resting memory CD4⁺ T cells. During latency, in addition to blocks at the initiation and elongation steps of viral transcription, there is a block in the export of viral RNA (vRNA), leading to the accumulation of multiply-spliced transcripts in the nucleus. Two of the genes encoded by the multiply-spliced transcripts are Tat and Rev, which are essential early in the viral replication cycle and might indicate the state of infection in a given population of cells. Here, the levels of multiply-spliced transcripts were compared to the levels of gag-containing RNA in tissue samples from RT-SHIV-infected rhesus macaques treated with HAART. Splice site sequence variation was identified during development of a TaqMan PCR assay. Multiply-spliced transcripts were detected in gastrointestinal and lymphatic tissues, but not the thymus. Levels of multiply-spliced transcripts were lower than levels of gag RNA, and both correlated with plasma virus loads. The ratio of multiply-spliced to gag RNA was greatest in the gastrointestinal samples from macaques with plasma virus loads

Rewards-based crowdfunding presents an information asymmetry for participants due to the funding mechanism used. Campaign-backers trust creators to complete projects and deliver rewards as outlined prior to the fundraising process, but creators may discover better opportunities as they progress with a project. Despite this, the all-or-nothing (AON) mechanism on crowdfunding platforms incentivizes creators to set meager funding-targets that are easier to achieve but may offer limited slack when creators wish to simultaneously pursue emerging opportunities later in the project. We explore the related issues of how funding targets seem to be selected by the creators, and how dissatisfaction with the rewards outcomes may arise for the backers. We constructed a quasi-experimental (QE) research design based on an extensive dataset from Kickstarter with nearly 390,000 campaigns. Our findings show that creators who set particularly meager funding-targets for their campaigns are more likely to receive sufficient funds but are less likely to satisfy backers with the project outcomes they deliver. We also test the moderating roles of creator and campaign characteristics. Overall, this study provides evidence that the funding mechanism used in rewards-based crowdfunding may be unsustainable in its current form, unless new mechanisms are introduced to realign the diverging incentives for creators and backers. [ABSTRACT FROM AUTHOR]

Effective market mechanisms are important for supporting the high performance and profitability of digital commerce firms, just as they have been for traditional buyer-seller exchange networks that maximize overall welfare and optimize the distribution of goods and services so firms can sustain viable businesses [[5], [12]]. Interestingly however, there is no evidence that more post-campaign comments (suggesting ongoing creator-backer alignment) led to higher backer satisfaction, nor were experienced campaign creators likely to moderate the effects of low funding targets on backer satisfaction. [Extracted from the article]