The emergence of Internet-based social media has made it possible for one person to communicate with hundreds or even thousands of other people about products and the companies that provide them. ...Thus, the impact of consumer-to-consumer communications has been greatly magnified in the marketplace. This article argues that social media is a hybrid element of the promotion mix because in a traditional sense it enables companies to talk to their customers, while in a nontraditional sense it enables customers to talk directly to one another. The content, timing, and frequency of the social media-based conversations occurring between consumers are outside managers’ direct control. This stands in contrast to the traditional integrated marketing communications paradigm whereby a high degree of control is present. Therefore, managers must learn to shape consumer discussions in a manner that is consistent with the organization's mission and performance goals. Methods by which this can be accomplished are delineated herein. They include providing consumers with networking platforms, and using blogs, social media tools, and promotional tools to engage customers.
The use of mobile devices by consumers and the accompanying response by retailers is rapidly revolutionizing the retail environment. In the past, retailers have focused primarily on the outcome (to ...purchase or not to purchase) of the consumer decision process, but now mobile technologies give retailers the opportunity to more actively influence the entire consumer decision-making processes. The increasing use of mobile devices by consumers makes shopping a continuous rather than discrete activity that requires retailers to engage with their customers at critical touch points of the decision process in order to provide a more customer-centric experience. This change in focus from the decision outcome to the decision process signifies an important paradigm shift for the retailing industry. After an extensive review of the literature, we identify four pillars that form the foundation for the mobile shopping revolution and represent the essential ways and means through which retailers can engage with consumers during the decision process. We also discuss the different areas in which the pillars can enable retailers to achieve a sustainable competitive advantage in the mobile shopping era.
Drug-induced liver injury (DILI) is a challenge in clinical medicine and drug development. Highly sensitive novel biomarkers have been identified for detecting DILI following a paracetamol overdose. ...The study objective was to evaluate biomarker performance in a 14-day trial of therapeutic dose paracetamol. The PATH-BP trial was a double-blind, placebo-controlled, crossover study. Individuals (n = 110) were randomized to receive 1 g paracetamol 4× daily or matched placebo for 2 weeks followed by a 2-week washout before crossing over to the alternate treatment. Blood was collected on days 0 (baseline), 4, 7, and 14 in both arms. Alanine transaminase (ALT) activity was measured in all patients. MicroRNA-122 (miR-122), cytokeratin-18 (K18), and glutamate dehydrogenase (GLDH) were measured in patients who had an elevated ALT on paracetamol treatment (≥50% from baseline). ALT increased in 49 individuals (45%). All 3 biomarkers were increased at the time of peak ALT (K18 paracetamol arm: 18.9 ± 9.7 ng/ml, placebo arm: 11.1 ± 5.4 ng/ml, ROC-AUC = 0.80, 95% CI 0.71-0.89; miR-122: 15.1 ± 12.9fM V 4.9 ± 4.7fM, ROC-AUC = 0.83, 0.75-0.91; and GLDH: 24.6 ± 31.1U/l V 12.0 ± 11.8U/l, ROC-AUC = 0.66, 0.49-0.83). All biomarkers were correlated with ALT (K18 r = 0.68, miR-122 r = 0.67, GLDH r = 0.60). To assess sensitivity, biomarker performance was analyzed on the visit preceding peak ALT (mean 3 days earlier). K18 identified the subsequent ALT increase (K18 ROC-AUC = 0.70, 0.59-0.80; miR-122 ROC-AUC = 0.60, 0.49-0.72, ALT ROC-AUC = 0.59, 0.48-0.70; GLDH ROC-AUC = 0.70, 0.50-0.90). Variability was lowest for ALT and K18. In conclusion, K18 was more sensitive than ALT, miR-122, or GLDH and has potential significant utility in the early identification of DILI in trials and clinical practice.
Despite the clinical benefit of androgen‐deprivation therapy (ADT), the majority of patients with advanced prostate cancer (PCa) ultimately develop lethal castration‐resistant prostate cancer (CRPC). ...In this study, we identified thioesterase superfamily member 6 (THEM6) as a marker of ADT resistance in PCa. THEM6 deletion reduces in vivo tumour growth and restores castration sensitivity in orthograft models of CRPC. Mechanistically, we show that the ER membrane‐associated protein THEM6 regulates intracellular levels of ether lipids and is essential to trigger the induction of the ER stress response (UPR). Consequently, THEM6 loss in CRPC cells significantly alters ER function, reducing de novo sterol biosynthesis and preventing lipid‐mediated activation of ATF4. Finally, we demonstrate that high THEM6 expression is associated with poor survival and correlates with high levels of UPR activation in PCa patients. Altogether, our results highlight THEM6 as a novel driver of therapy resistance in PCa as well as a promising target for the treatment of CRPC.
Synopsis
Resistance to androgen‐deprivation therapy (ADT) leads to the development of lethal castration‐resistant prostate cancer. This study highlights THEM6 as a clinically relevant protein that supports ADT‐induced rewiring of lipid metabolism and sustains UPR activation, thus promoting ADT resistance.
THEM6 is overexpressed in ADT‐resistant tumours and supports PCa tumour growth in androgen‐deprived conditions.
Loss of THEM6 significantly alters the cellular lipidome of CRPC cells, resulting in decreased levels of ether lipids.
THEM6 is an ER‐membrane protein that physically interacts with several components of the protein trafficking machinery.
Loss of THEM6 significantly affects ER function, reducing de novo sterol synthesis and impairing lipid‐mediated activation of the UPR, two processes that promote ADT resistance.
High THEM6 expression in tumour biopsies is associated with shortened patient survival and correlates with sustained UPR activation, thus highlighting the potential of THEM6 as a therapeutic target in CRPC.
Resistance to androgen‐deprivation therapy (ADT) leads to the development of lethal castration‐resistant prostate cancer. This study highlights THEM6 as a clinically relevant protein that supports ADT‐induced rewiring of lipid metabolism and sustains UPR activation, thus promoting ADT resistance.
The low-frequency (terahertz) vibrational spectroscopy has been investigated experimentally for two chlorophyll species, Chl-
a
and one of its magnesium derivatives (Chl-Mg-Na). The combination of ...terahertz time-domain spectroscopy and Fourier transform infrared spectroscopy has enabled a broad frequency range to be covered (0.2 to 18 THz). For Chl-Mg-Na, the terahertz spectra show clear and well-marked features at 1.44, 1.64, and 1.83 THz dominated by intermolecular interactions. The frequency dependent refractive index and absorption coefficient of Chl-Mg-Na were both determined using the Fit@TDS software. Below 1.0 THz, a refractive index of 2.09 was measured. In order to acquire further understanding of the observed vibrational modes, a detailed study of the temperature dependence of the line positions of the lowest modes in Chl-Mg-Na was performed. As the temperature was increased from 88 K to 298 K, the feature at 1.83 THz experienced a notable red shift of frequency and line shape broadening, whereas the feature at 1.44 THz showed little change. These results suggest that the 1.83 THz feature is dominated by intermolecular motions occurring over the crystalline unit cell of the Chl-Mg-Na molecular crystal. Finally, terahertz time-domain spectroscopy was used to acquire the spectra of an ornamental plant bearing yellow-green variegated leaves (ivy,
Aureomarginata
variety), the yellow sectors having lower chlorophyll content compared to the green sectors. In dehydrated green tissue, the chlorophyll molecules showed well-marked intermolecular vibrational modes at 1.86 THz, indicating that chlorophyll molecules are prone to packing with an ordered molecular arrangement. These results demonstrate the potential application of THz spectroscopy in the field of agronomy.
This paper presents the results of a three-year research and teaching effort that focused on measuring the perceived effectiveness of Skype as a delivery platform for presentations made to students ...enrolled in a Professional MBA program by nationally acclaimed authors working in the area of social media. The research also investigated the authors' acceptance of Skype as a platform for delivering remote presentations to college audiences. The results indicated that both students and authors strongly supported the use of Skype as a presentation platform. The author presentations greatly enhanced the learning environment and contributed to achieving several specific course objectives.
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