Managing high-end ex-demonstration product returns

Some manufacturers demonstrate their products so that customers can gain experience before making a purchase. We present a novel application of a closed-loop supply chain where product returns from demonstrations of high-end IT equipment are substantial and the major delay in the system is due to the long demonstration time at the client sites. In addition, the product lifecycle is short and the value erodes rapidly over time, with steep drops in the resale revenue when new product generations are introduced. We present a finite lifecycle model that captures the key trade-offs in this environment, that is, either to reuse a collected ex-demo product for a next demonstration or to salvage its residual value in the secondary market and use a new product to satisfy the next demo request. We derive two cost/revenue signals that enable us to distinguish between fast and slow value erosion. We show that the fast/slow erosion decision is dynamic and depends on the rate of value erosion and the length of the demonstration time. We analyze the optimal demo pool strategies and show that in the case of fast erosion it may be better to postpone reuse activities until later in the lifecycle. We illustrate our model using empirical data from a large IT manufacturer and formulate several guidelines so as to better manage high value ex-demonstration product returns

Best Performance Frontiers for Buy-Online-Pickup-in-Store order fulfilment

With the proliferation of omni-channel retailing, Buy-Online-Pickup-in-Store (BOPS) retail services have gained increasing popularity as they have benefits for both customers and retailers. However, using conventional retail stores to fulfil orders received online whilst also serving walk-in customers is challenging for retailers, particularly when a high customer service level is promised to online customers (e.g., order by a certain time and pick up in store after a specific time later the same day). This paper examines store picking operations for same day BOPS services. Specifically, we derive Best Performance Frontiers (BPFs) for single wave and multi-wave order picking. New relationships, propositions, and results are presented to determine the minimum picking rate needed in stores to guarantee a target service level, the number of picking waves a retailer should launch in an ordering cycle, and the timing of picking waves. We also examine demand surge scenarios with different order arrival rates in an ordering cycle. Insights and implications of the results are discussed for retailers that seek to benchmark their current BOPS performances and understand how to schedule and improve the picking of online orders in conventional retail stores and the picking rates needed to guarantee a desired service level for online customers

Electrochemical detection of Toxocara canis excretory-secretory antigens in children from rural communities in Esmeraldas Province, Ecuador: association between active infection and high eosinophilia.

BACKGROUND: The diagnosis of active Toxocara canis infections in humans is challenging. Larval stages of T. canis do not replicate in human tissues and disease may result from infection with a single T. canis larva. Recently, we developed a nanobody-based electrochemical magnetosensor assay with superior sensitivity to detect T. canis excretory-secretory (TES) antigens. Here, we evaluate the performance of the assay in children from an Ecuadorian birth cohort that followed children to five years of age. METHODS: Samples were selected based on the presence of peripheral blood eosinophilia and relative eosinophil counts. The samples were analyzed by the nanobody-based electrochemical magnetosensor assay, which utilizes a bivalent biotinylated nanobody as capturing agent on the surface of streptavidin pre-coated paramagnetic beads. Detection was performed by a different nanobody chemically labelled with horseradish peroxidase. RESULTS: Of 87 samples tested, 33 (38%) scored positive for TES antigen recognition by the electrochemical magnetosensor assay. The average concentration of TES antigen in serum was 2.1 ng/ml (SD = 1.1). The positive result in the electrochemical assay was associated with eosinophilia > 19% (P = 0.001). Parasitological data were available for 57 samples. There was no significant association between positivity by the electrochemical assay and the presence of other soil-transmitted helminth infections. CONCLUSIONS: Our nanobody-based electrochemical assay provides highly sensitive quantification of TES antigens in serum and has potential as a valuable tool for the diagnosis of active human toxocariasis

Intrabody targeting HIF-1α mediates transcriptional downregulation of target genes related to solid tumors

Uncontrolled growth of solid tumors will result in a hallmark hypoxic condition, whereby the key transcriptional regulator of hypoxia inducible factor-1α (HIF-1α) will be stabilized to activate the transcription of target genes that are responsible for the metabolism, proliferation, and metastasis of tumor cells. Targeting and inhibiting the transcriptional activity of HIF-1 may provide an interesting strategy for cancer therapy. In the present study, an immune library and a synthetic library were constructed for the phage display selection of Nbs against recombinant PAS B domain protein (rPasB) of HIF-1α. After panning and screening, seven different nanobodies (Nbs) were selected, of which five were confirmed via immunoprecipitation to target the native HIF-1α subunit. The inhibitory effect of the selected Nbs on HIF-1 induced activation of target genes has been evaluated after intracellular expression of these Nbs in HeLa cells. The dramatic inhibition of both intrabody formats on the expression of HIF-1-related target genes has been confirmed, which indicated the inhibitory efficacy of selected Nbs on the transcriptional activity of HIF-1. © 2021 by the authors. Licensee MDPI, Basel, Switzerland

A nanobody-based tracer targeting DPP6 for non-invasive imaging of human pancreatic endocrine cells

There are presently no reliable ways to quantify endocrine cell mass (ECM) in vivo, which prevents an accurate understanding of the progressive beta cell loss in diabetes or following islet transplantation. To address this unmet need, we coupled RNA sequencing of human pancreatic islets to a systems biology approach to identify new biomarkers of the endocrine pancreas. Dipeptidyl-Peptidase 6 (DPP6) was identified as a target whose mRNA expression is at least 25-fold higher in human pancreatic islets as compared to surrounding tissues and is not changed by proinflammatory cytokines. At the protein level, DPP6 localizes only in beta and alpha cells within the pancreas. We next generated a high-affinity camelid single-domain antibody (nanobody) targeting human DPP6. The nanobody was radiolabelled and in vivo SPECT/CT imaging and biodistribution studies were performed in immunodeficient mice that were either transplanted with DPP6-expressing Kelly neuroblastoma cells or insulin-producing human EndoC-βH1 cells. The human DPP6-expressing cells were clearly visualized in both models. In conclusion, we have identified a novel beta and alpha cell biomarker and developed a tracer for in vivo imaging of human insulin secreting cells. This provides a useful tool to non-invasively follow up intramuscularly implanted insulin secreting cells

Exploiting nanobodies and Affimers for superresolution imaging in light microscopy

Antibodies have long been the main approach used for localizing proteins of interest by light microscopy. In the past 5 yr or so, and with the advent of superresolution microscopy, the diversity of tools for imaging has rapidly expanded. One main area of expansion has been in the area of nanobodies, small single-chain antibodies from camelids or sharks. The other has been the use of artificial scaffold proteins, including Affimers. The small size of nanobodies and Affimers compared with the traditional antibody provides several advantages for superresolution imaging