Service capacity procurement of logistics service supply chain with demand updating and loss-averse preference

This research aims to identify the impacts of loss-averse preference on the service capacity procurement decisions with demand updating in a logistics service supply chain, which consists of one logistics service integrator and one functional logistics service provider. It starts from a basic two-stage Stackelberg game model, then, extends to three scenarios where either the integrator or the provider or neither of them has loss-averse preference. The impact of loss-averse preference on the decisions of supply chain members is discussed by comparing the four models. Our results reveal, first, the loss-averse preferences do not always affect the decisions of supply chain members. If certain conditions are satisfied, the logistics service integrator can benefit from its loss-averse preference. Second, the increased service level can affect the logistics service integrator’s procurement strategy and the functional logistics service provider’s pricing strategy. This effect is only related to the loss-averse preference of the functional logistics service provider. Last, under certain conditions, the total service capacity decreases with the increased service level, regardless of whether or not the supply chain members have loss-averse preferences

Pricing decision with conspicuous customers: quick responses versus value-added services

In order to eliminate the negative effects of customer strategic behavior, retailers often adopt quick response or value-added services. While in a luxury market with conspicuous customers, retailers’ pricing decisions of these two strategies become more complicated. This paper studies a supply chain with a retailer serving a mixture of conspicuous and ordinary strategic customers. We develop three models so that the retailer provides i) neither quick response nor value-added services; ii) only quick response; iii) only value-added services. Subsequently, we analyze the impacts of conspicuous customers on quick response and value-added services by pricing and strategy comparisons. The model further extends to the situation including both strategies. The results show that, firstly, when the proportion is less than a threshold, the retailer should adopt a low price strategy, and vice versa. Besides, the quick response could induce the retailer to adopt high price while value-added services inhibit it. Secondly, the customer conspicuous behavior can motivate retailers to provide quick response and inhibit their value-added services. Finally, by observing the retailer’s decisions when they can adopt two strategies simultaneously, we find that the existence of quick response can amplify the benefits of value-added services

Aneuploid Embryonic Stem Cells Drive Teratoma Metastasis

Aneuploidy, a deviation of the chromosome number from euploidy, is one of the hallmarks of cancer. High levels of aneuploidy are generally correlated with metastasis and poor prognosis in cancer patients. However, the causality of aneuploidy in cancer metastasis remains to be explored. Here we demonstrate that teratomas derived from aneuploid murine embryonic stem cells (ESCs), but not from isogenic diploid ESCs, disseminated to multiple organs, for which no additional copy number variations were required. Notably, no cancer driver gene mutations were identified in any metastases. Aneuploid circulating teratoma cells were successfully isolated from peripheral blood and showed high capacities for migration and organ colonization. Single-cell RNA sequencing of aneuploid primary teratomas and metastases identified a unique cell population with high stemness that was absent in diploid ESCs-derived teratomas. Further investigation revealed that aneuploid cells displayed decreased proteasome activity and overactivated endoplasmic reticulum (ER) stress during differentiation, thereby restricting the degradation of proteins produced from extra chromosomes in the ESC state and causing differentiation deficiencies. Noticeably, both proteasome activator Oleuropein and ER stress inhibitor 4-PBA can effectively inhibit aneuploid teratoma metastasis

Sequencing and Genetic Variation of Multidrug Resistance Plasmids in Klebsiella pneumoniae

BACKGROUND: The development of multidrug resistance is a major problem in the treatment of pathogenic microorganisms by distinct antimicrobial agents. Characterizing the genetic variation among plasmids from different bacterial species or strains is a key step towards understanding the mechanism of virulence and their evolution. RESULTS: We applied a deep sequencing approach to 206 clinical strains of Klebsiella pneumoniae collected from 2002 to 2008 to understand the genetic variation of multidrug resistance plasmids, and to reveal the dynamic change of drug resistance over time. First, we sequenced three plasmids (70 Kb, 94 Kb, and 147 Kb) from a clonal strain of K. pneumoniae using Sanger sequencing. Using the Illumina sequencing technology, we obtained more than 17 million of short reads from two pooled plasmid samples. We mapped these short reads to the three reference plasmid sequences, and identified a large number of single nucleotide polymorphisms (SNPs) in these pooled plasmids. Many of these SNPs are present in drug-resistance genes. We also found that a significant fraction of short reads could not be mapped to the reference sequences, indicating a high degree of genetic variation among the collection of K. pneumoniae isolates. Moreover, we identified that plasmid conjugative transfer genes and antibiotic resistance genes are more likely to suffer from positive selection, as indicated by the elevated rates of nonsynonymous substitution. CONCLUSION: These data represent the first large-scale study of genetic variation in multidrug resistance plasmids and provide insight into the mechanisms of plasmid diversification and the genetic basis of antibiotic resistance

Mesoporous nitrogen-doped TiO2 sphere applied for quasi-solid-state dye-sensitized solar cell

A mesoscopic nitrogen-doped TiO2 sphere has been developed for a quasi-solid-state dye-sensitized solar cell [DSSC]. Compared with the undoped TiO2 sphere, the quasi-solid-state DSSC based on the nitrogen-doped TiO2 sphere shows more excellent photovoltaic performance. The photoelectrochemistry of electrodes based on nitrogen-doped and undoped TiO2 spheres was characterized with Mott-Schottky analysis, intensity modulated photocurrent spectroscopy, and electrochemical impedance spectroscopy, which indicated that both the quasi-Fermi level and the charge transport of the photoelectrode were improved after being doped with nitrogen. As a result, a photoelectric conversion efficiency of 6.01% was obtained for the quasi-solid-state DSSC

The Protection of Midazolam Against Immune Mediated Liver Injury Induced by Lipopolysaccharide and Galactosamine in Mice

Objectives: Liver macrophages agitated by Lipopolysaccharide (LPS) can enhance immuno-inflammatory responses in the liver which mediate liver injury and result in dysfunction. Midazolam has been reported to have inhibitory effects on activated immunity and escalated inflammation, however, what the effects of midazolam on the liver injury caused by excessive immuno-inflammatory response in sepsis, and what influence it will exert on inflamed liver macrophages need to be elucidated.Methods: In the present study, LPS and galactosamine-induced acute liver injury mice were used to observe the effect of midazolam in vivo. LPS-stimulated bone marrow cells were used to evaluate the influence of midazolam on monocytes in vitro.Results: Midazolam prevented liver tissue injury and decreased serum alanine transaminase (ALT) level in LPS plus galactosamine treated mice. Mechanistically, midazolam suppressed tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) produced by LPS stimulated liver macrophages in vivo and bone marrow monocytes in vitro, and reduced the expression of major histocompatibility complex class II (MHC II), cluster of differentiation 40 and 86 (CD40 and CD86) on the cell surface. These results could be reversed by PK-11195, a peripheral benzodiazepine receptor (PBR) blocker.Conclusion: Midazolam can prevent liver from LPS-induced immune mediated liver injury by inhibiting inflammation and immune activation in liver macrophages

Impacts of Hypoxia-Inducible Factor-1 Knockout in the Retinal Pigment Epithelium on Choroidal Neovascularization

PURPOSE. Hypoxia-inducible factor (HIF)-1 is a key oxygen sensor and is believed to play an important role in neovascularization (NV). The purpose of this study is to determine the role of retinal pigment epithelium (RPE)-derived HIF-1a on ocular NV. METHODS. Conditional HIF-1a knockout (KO) mice were generated by crossing transgenic mice expressing Cre in the RPE with HIF-1a floxed mice, confirmed by immunohistochemistry, Western blot analysis, and fundus fluorescein angiography. The mice were used for the oxygen-induced retinopathy (OIR) and laser-induced choroidal neovascularization (CNV) models. RESULTS. HIF-1a levels were significantly decreased in the RPE layer of ocular sections and in primary RPE cells from the HIF1a KO mice. Under normal conditions, the HIF-1a KO mice exhibited no apparent abnormalities in retinal histology or visual function as shown by light microscopy and electroretinogram recording, respectively. The HIF-1a KO mice with OIR showed no significant difference from the wild-type (WT) mice in retinal levels of HIF-1a and VEGF as well as in the number of preretinal neovascular cells. In the laser-induced CNV model, however, the disruption of HIF-1a in the RPE attenuated the over expression of VEGF and the intercellular adhesion molecule 1 (ICAM-1), and reduced vascular leakage and CNV area. CONCLUSIONS. RPE-derived HIF-1a plays a key role in CNV, but not in ischemia-induced retinal NV. (Invest Ophthalmol Vis Sci

The role of RhoA/Rho kinase pathway in endothelial dysfunction

Endothelial dysfunction is a key event in the development of vascular disease, and it precedes clinically obvious vascular pathology. Abnormal activation of the RhoA/Rho kinase (ROCK) pathway has been found to elevate vascular tone through unbalancing the production of vasodilating and vasoconstricting substances. Inhibition of the RhoA/ROCK pathway can prevent endothelial dysfunction in a variety of pathological conditions. This review, based on recent molecular, cellular, and animal studies, focuses on the current understanding of the ROCK pathway and its roles in endothelial dysfunction

Cassava genome from a wild ancestor to cultivated varieties

Cassava is a major tropical food crop in the Euphorbiaceae family that has high carbohydrate production potential and adaptability to diverse environments. Here we present the draft genome sequences of a wild ancestor and a domesticated variety of cassava and comparative analyses with a partial inbred line. We identify 1,584 and 1,678 gene models specific to the wild and domesticated varieties, respectively, and discover high heterozygosity and millions of single-nucleotide variations. Our analyses reveal that genes involved in photosynthesis, starch accumulation and abiotic stresses have been positively selected, whereas those involved in cell wall biosynthesis and secondary metabolism, including cyanogenic glucoside formation, have been negatively selected in the cultivated varieties, reflecting the result of natural selection and domestication. Differences in microRNA genes and retrotransposon regulation could partly explain an increased carbon flux towards starch accumulation and reduced cyanogenic glucoside accumulation in domesticated cassava. These results may contribute to genetic improvement of cassava through better understanding of its biology