RESUMEN
Many studies propose methods for finding the best location for new stores and facilities, but few studies address the store closing problem. As a result of the recent COVID-19 pandemic, many companies have been facing financial issues. In this situation, one of the most common solutions to prevent loss is to downsize by closing one or more chain stores. Such decisions are usually made based on single-store performance; therefore, the under-performing stores are subject to closures. This study first proposes a multiplicative variation of the well-known Huff gravity model and introduces a new attractiveness factor to the model. Then a forward-backward approach is used to train the model and predict customer response and revenue loss after the hypothetical closure of a particular store from a chain. In this research the department stores in New York City are studied using large-scale spatial, mobility, and spending datasets. The case study results suggest that the stores recommended being closed under the proposed model may not always match the single store performance, and emphasizes the fact that the performance of a chain is a result of interaction among the stores rather than a simple sum of their performance considered as isolated and independent units. The proposed approach provides managers and decision-makers with new insights into store closing decisions and will likely reduce revenue loss due to store closures.
RESUMEN
Context ⢠Telomeres are repeated deoxyribonucleic acid (DNA) sequences (TTAGGG) that are located on the 5' ends of chromosomes, and they control the life span of eukaryotic cells. Compelling evidence has shown that the length of a person's life is dictated by the limited number of times that a human cell can divide. The enzyme telomerase has been shown to bind to and extend the length of telomeres. Thus, strategies for activating telomerase may help maintain telomere length and, thus, may lead to improved health during aging. Objective ⢠The current study intended to investigate the effects of several natural compounds on telomerase activity in an established cell model of telomere shortening (ie, IMR90 cells). Design ⢠The research team designed an in vitro study. Setting ⢠The study was conducted at Roskamp Institute in Sarasota, FL, USA. Intervention ⢠The tested single compounds were (1) α-lipoic acid, (1) green tea extract, (2) dimethylaminoethanol L-bitartrate (DMAE L-bitartrate), (3) N-acetyl-L-cysteine hydrochloride (HCL), (4) chlorella powder, (5) L-carnosine, (6) vitamin D3, (7) rhodiola PE 3%/1%, (8) glycine, (9) French red wine extract, (10) chia seed extract, (11) broccoli seed extract, and (12) Astragalus (TA-65). The compounds were tested singly and as blends. Outcome Measures ⢠Telomerase activity for single compounds and blends of compounds was measured by the TeloTAGGG telomerase polymerase chain reaction (PCR) enzyme-linked immunosorbent assay (ELISA). The 4 most potent blends were investigated for their effects on cancer-cell proliferation and for their potential effects on the cytotoxicity and antiproliferative activity of a chemotherapeutic agent, the topoisomerase I inhibitor topotecan. The benefits of 6 population doublings (PDs) were measured for the single compounds, and the 4 blends were compared to 3 concentrations of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Results ⢠Certain of the compounds increased telomerase activity, and combinations of the top-ranking compounds were able to increase telomerase activity significantly, from 51% to 290%, relative to controls. Conclusions ⢠The results have confirmed that many naturally occurring compounds hold the potential to activate telomerase and that certain of those compounds have demonstrated synergistic effects to produce more potent blends. Given the relationship between telomere shortening, aging, and the decline of tissue function, it is reasonable to hypothesize that such telomerase-activating blends may have health-promoting benefits, particularly in relation to aging-associated conditions. Further investigation of such blends in human studies that are designed to evaluate safety and the effects on telomere length are thus warranted.
Asunto(s)
Antineoplásicos/farmacología , Telomerasa/efectos de los fármacos , Telómero/efectos de los fármacos , Células Cultivadas , Chlorella , Humanos , Neoplasias , Telomerasa/metabolismoRESUMEN
Gulf War Illness (GWI) is a chronic multisymptom illness with a central nervous system component such as memory deficits, neurological, and musculoskeletal problems. There are ample data that demonstrate that exposure to Gulf War (GW) agents, such as pyridostigmine bromide (PB) and pesticides such as permethrin (PER), were key contributors to the etiology of GWI post deployment to the Persian GW. In the current study, we examined the consequences of acute (10 days) exposure to PB and PER in C57BL6 mice. Learning and memory tests were performed at 18 days and at 5 months post-exposure. We investigated the relationship between the cognitive phenotype and neuropathological changes at short and long-term time points post-exposure. No cognitive deficits were observed at the short-term time point, and only minor neuropathological changes were detected. However, cognitive deficits emerged at the later time point and were associated with increased astrogliosis and reduction of synaptophysin staining in the hippocampi and cerebral cortices of exposed mice, 5 months post exposure. In summary, our findings in this mouse model of GW agent exposure are consistent with some GWI symptom manifestations, including delayed onset of symptoms and CNS disturbances observed in GWI veterans.
Asunto(s)
Corteza Cerebral/fisiopatología , Hipocampo/fisiopatología , Memoria a Largo Plazo/efectos de los fármacos , Permetrina/toxicidad , Síndrome del Golfo Pérsico/fisiopatología , Bromuro de Piridostigmina/toxicidad , Animales , Astrocitos/efectos de los fármacos , Astrocitos/metabolismo , Astrocitos/patología , Corteza Cerebral/efectos de los fármacos , Corteza Cerebral/metabolismo , Corteza Cerebral/patología , Cognición/efectos de los fármacos , Modelos Animales de Enfermedad , Expresión Génica , Guerra del Golfo , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , Hipocampo/patología , Humanos , Masculino , Memoria a Corto Plazo/efectos de los fármacos , Ratones , Ratones Endogámicos C57BL , Síndrome del Golfo Pérsico/inducido químicamente , Síndrome del Golfo Pérsico/metabolismo , Síndrome del Golfo Pérsico/patología , Sinaptofisina/antagonistas & inhibidores , Sinaptofisina/genética , Sinaptofisina/metabolismo , Factores de TiempoRESUMEN
The CD40 receptor is a member of the tumor necrosis factor (TNF) super-family of trans-membrane receptors. Interaction of CD40 with its ligand CD40L mediates a broad range of immune and inflammatory responses in the periphery and in the central nervous system. Recently it has been suggested that CD40/CD40L interaction is involved in amyloid precursor protein (APP) processing and Alzheimer's disease (AD)-like pathology in transgenic mouse models of AD. We have previously shown that pharmacologically inhibiting CD40/CD40L interaction improves memory deficits in the PSAPP AD mouse model. We have also recently shown that CD40 deficiency mitigates amyloid deposition in APPsw and PSAPP mouse models. In the present report, using human embryonic kidney cells (HEK293) over-expressing both the APPsw mutation and CD40, we demonstrate that CD40/CD40L interaction directly increases the production of APP metabolites (Abeta 1-40, Abeta 1-42, CTFs, sAPPbeta and sAPPalpha). The results also show that CD40/CD40L interaction affects APP processing via the NF-kappaB pathway. Using NFkappaB inhibitors and SiRNAs to silence diverse elements of the NFkappaB pathway, we observe a reduction in levels of both Abeta 1-40 and Abeta 1-42. Taken together, our results further suggest that CD40L stimulation may be a key component in AD pathology and that elements of the NF-kappaB pathway may be suitable targets for therapeutic approaches against AD.