Essays on dynamic sales mechanisms

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Economics, 2009.Includes bibliographical references.This thesis is a collection of three essays on dynamic sales mechanisms. The first chapter analyzes the Name Your Own Price (NYOP) mechanism adopted by Priceline.com. Priceline.com, a website helping travelers obtain discount rates for travel-related items, gained prominence for its Name Your Own Price system. Under Name Your Own Price, a traveler names his price for airline tickets, hotel rooms, or car rentals. Priceline then checks if there is any seller willing to accept the offer. If no one accepts, the buyer has to wait for a certain period of time (the lockout period) before rebidding. This paper builds a one-to-many dynamic model without commitment to examine the buyer's and the sellers' equilibrium strategies. I show that without a lockout period, in equilibrium, the sellers with different costs are either almost fully discriminated or pooled in intervals except the one with the lowest possible cost. In the latter case, the buyer does not raise the bids much until the very end, so the price pattern is convexly increasing, consistent with the empirical finding, and most transactions occur just before the day of the trip, which illustrates the deadline effect that is observed in many negotiation processes. The lockout period restriction, which limits the buyer's bidding chances and seems to hurt the buyer, thus moves the transactions forward and can actually benefit a buyer in some circumstances. The second chapter studies a one-to-many negotiation process in which a seller with an indivisible object negotiates with two asymmetric buyers to determine who gets the object and at what price.(cont.) The seller repeatedly submits take-it-or-leave-it offers to the two buyers until one of them accepts. Unlike a Dutch auction, the seller has the discretion to offer two different prices to the two buyers. I show that when committing to some price paths is possible, the optimal outcome for the seller stated by Myerson (1981) is achievable. When commitment is impossible, the optimal outcome is no longer attainable. Instead, there exists an equilibrium in which the seller's equilibrium payoff is the same as that in a second-price auction, which implies that the seller's payoff might be lower than in a Dutch auction. The result thus illustrates the value of a simple institution like a Dutch auction, which seems to restrict a player's freedom but actually benefits the player by providing a commitment tool. The analysis also sheds light on the procurement literature. The third chapter provides a rationale for why a seller may package goods in bundles that are too large for a consumer to consume all by himself. I show that selling in bulk packages is an alternative way for the seller to discriminate buyers when resale cannot be excluded among buyers. When bulk packages are offered, buyers who value the product more usually have stronger incentive to buy the package, and buyers who value the product less tend to buy from resale. Moreover, the seller can make more profit by selling bulk packages than by selling single-unit packages when the buyers' values of the product are more negatively correlated.by Chia-Hui Chen.Ph.D

In vivo cofactor biosynthesis and maintenance in the class Ia ribonucleotide reductase small subunit of Escherichia coli

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemistry, 2009.This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections.Vita.Includes bibliographical references.The small subunit ([beta]2) of Escherichia coli class Ia ribonucleotide reductases (RNRs) contains a diferric tyrosyl radical (Y*) cofactor essential for the conversion of nucleotides to deoxynucleotides that are needed for DNA synthesis and repair. The mechanism and factors involved in the biosynthesis, maintenance and regulation of this cluster remains unclear. To understand these pathways, the genes contiguous to nrdB (gene encoding [beta]) in 181 bacterial genomes were analyzed which revealed a highly conserved [2Fe2S]-ferredoxin, YfaE in E. coli. YfaE has been cloned, expressed, reconstituted, and characterized by UV-visible, EPR and Mössbauer spectroscopies. Titration of met-[beta]2 (an inactive diferric-[beta]2 with Y* reduced) with [2Fe2S]1+-YfaE results in formation of diferrous-[beta]2 with one Fe reduced/YfaE oxidized. At the end point of titration, exposure of the reduced cluster to O2 in the absence of an additional reducing equivalent yields the diferric-Y* with 2 Fe/Y* generated, suggesting that the reducing equivalent required for cluster assembly is supplied by [beta]2, likely by W48. The kobs for the reaction between met-[beta]2 and [2Fe2S]1+-YfaE determined by anaerobic stopped flow spectroscopy is ~1-5 s-1. Studies of conserved Lys to Ala mutations of [beta]2 indicate electrostatic interactions may play an important role for interaction with YfaE. Quantitative Western blots of the whole cells suggest that YfaE acts catalytically in reactivating met-[beta]2 in vivo. Titration experiments establish that met-[beta]2 can be reduced by catalytic amounts of YfaE, Fre (a flavin reductase) and flavin with consumption of NADPH. In the presence of a Y* scavenger, hydroxyurea, [delta]yfaE shows slower growth rates than the isogenic wt strain and Western blots analysis shows up-regulation of YfaE expression, supporting YfaE's role in the reactivation of diferric-[beta]2 in vivo. To investigate the iron sources for diferric-Y* assembly, changes in Fe pools inside the cell subsequent to expression of [beta]2 was monitored by whole cell Mössbauer spectroscopy. The results show that both Fe2+ and Fe3+ pools can provide the iron for cluster assembly, suggesting a reduction mechanism(s) for Fe3+ to allow it function in this capacity. A potential role of YfaE as an iron chaperone for iron delivery to [beta]2 has also been investigated.by Chia-Hung Wu.Ph.D

Pulse wave velocity is associated with increased plasma oxLDL in ageing but not with FGF21 and habitual exercise

Fibroblast growth factor 21 (FGF21) and adiponectin increase expression of genes involved in antioxidant pathways, but their roles in mediating oxidative stress and arterial stiffness with ageing and habitual exercise remain unknown. We explored the role of the FGF21–adiponectin axis in mediating oxidative stress and arterial stiffness with ageing and habitual exercise. Eighty age- and sex-matched healthy individuals were assigned to younger sedentary or active (18–36 years old,n=20 each) and older sedentary or active (45–80 years old,n=20 each) groups. Arterial stiffness was measured indirectly using pulse wave velocity (PWV). Fasted plasma concentrations of FGF21, adiponectin and oxidized low-density lipoprotein (oxLDL) were measured. PWV was 0.2-fold higher and oxLDL concentration was 25.6% higher (both p<0.001) in older than younger adults, despite no difference in FGF21 concentration (p=0.097) between age groups. PWV (p=0.09) and oxLDL concentration (p=0.275) did not differ between activity groups but FGF21 concentration was 9% lower in active than sedentary individuals (p=0.011). Adiponectin concentration did not differ by age (p=0.642) or exercise habits (p=0.821). In conclusion, age, but not habitual exercise, was associated with higher oxidative stress and arterial stiffness. FGF21 and adiponectin did not differ between younger and older adults, unlikely mediating oxidative stress and arterial stiffness in healthy adults. <br

Pharmacological levels of withaferin A (Withania somnifera) trigger clinically relevant anticancer effects specific to triple negative breast cancer cells

Withaferin A (WA) isolated from Withania somnifera (Ashwagandha) has recently become an attractive phytochemical under investigation in various preclinical studies for treatment of different cancer types. In the present study, a comparative pathway-based transcriptome analysis was applied in epithelial-like MCF-7 and triple negative mesenchymal MDA-MB-231 breast cancer cells exposed to different concentrations of WA which can be detected systemically in in vivo experiments. Whereas WA treatment demonstrated attenuation of multiple cancer hallmarks, the withanolide analogue Withanone (WN) did not exert any of the described effects at comparable concentrations. Pathway enrichment analysis revealed that WA targets specific cancer processes related to cell death, cell cycle and proliferation, which could be functionally validated by flow cytometry and real-time cell proliferation assays. WA also strongly decreased MDA-MB-231 invasion as determined by single-cell collagen invasion assay. This was further supported by decreased gene expression of extracellular matrix-degrading proteases (uPA, PLAT, ADAM8), cell adhesion molecules (integrins, laminins), pro-inflammatory mediators of the metastasis-promoting tumor microenvironment (TNFSF12, IL6, ANGPTL2, CSF1R) and concomitant increased expression of the validated breast cancer metastasis suppressor gene (BRMS1). In line with the transcriptional changes, nanomolar concentrations of WA significantly decreased protein levels and corresponding activity of uPA in MDA-MB-231 cell supernatant, further supporting its anti-metastatic properties. Finally, hierarchical clustering analysis of 84 chromatin writer-reader-eraser enzymes revealed that WA treatment of invasive mesenchymal MDA-MB-231 cells reprogrammed their transcription levels more similarly towards the pattern observed in non-invasive MCF-7 cells. In conclusion, taking into account that sub-cytotoxic concentrations of WA target multiple metastatic effectors in therapy-resistant triple negative breast cancer, WA-based therapeutic strategies targeting the uPA pathway hold promise for further (pre)clinical development to defeat aggressive metastatic breast cancer

Decreased Circulating Endothelial Progenitor Cell Levels and Function in Patients with Nonalcoholic Fatty Liver Disease

OBJECTIVES: Nonalcoholic fatty liver disease (NAFLD) is associated with advanced atherosclerosis and a higher risk of cardiovascular disease. Increasing evidence suggests that injured endothelial monolayer is regenerated by circulating bone marrow derived-endothelial progenitor cells (EPCs), and levels of circulating EPCs reflect vascular repair capacity. However, the relation between NAFLD and EPC remains unclear. Here, we tested the hypothesis that patients with nonalcoholic fatty liver disease (NAFLD) might have decreased endothelial progenitor cell (EPC) levels and attenuated EPC function. METHODS AND RESULTS: A total of 312 consecutive patients undergoing elective coronary angiography because of suspected coronary artery disease were screened and received examinations of abdominal ultrasonography between July 2009 and November 2010. Finally, 34 patients with an ultrasonographic diagnosis of NAFLD, and 68 age- and sex-matched controls without NAFLD were enrolled. Flow cytometry with quantification of EPC markers (defined as CD34(+), CD34(+)KDR(+), and CD34(+)KDR(+)CD133(+)) in peripheral blood samples was used to assess circulating EPC numbers. The adhesive function, and migration, and tube formation capacities of EPCs were also determined in NAFLD patients and controls. Patients with NAFLD had a significantly higher incidence of metabolic syndrome, previous myocardial infarction, hyperuricemia, and higher waist circumference, body mass index, fasting glucose and triglyceride levels. In addition, patients with NAFLD had significantly decreased circulating EPC levels (all P<0.05), attenuated EPC functions, and enhanced systemic inflammation compared to controls. Multivariate logistic regression analysis showed that circulating EPC level (CD34(+)KDR(+) [cells/10(5) events]) was an independent reverse predictor of NAFLD (Odds ratio: 0.78; 95% confidence interval: 0.69-0.89, P<0.001). CONCLUSIONS: NAFLD patients have decreased circulating EPC numbers and functions than those without NAFLD, which may be one of the mechanisms to explain atherosclerotic disease progression and enhanced cardiovascular risk in patients with NAFLD

Iterative joint frequency offset and channel estimation for OFDM systems using first and second order approximation algorithms

[[abstract]]To implement an algorithm for joint estimation of carrier frequency offset (CFO) and channel impulse response (CIR) in orthogonal frequency division multiplexing (OFDM) systems, the maximum-likelihood criterion is commonly adopted. A major difficulty arises from the highly nonlinear nature of the log-likelihood function which renders local extrema or multiple solutions for the CFO and CIR estimators. Use of an approximation method coupled with an adaptive iteration algorithm has been a popular approach to ease problem solving. The approximation used in those existing methods is usually of the first order level. Here, in addition to a new first order approximation method, we also propose a second order approximation method. Further, for the part of the adaptive iteration algorithm, we adopt a new technique which will enable performance improvement. Our first order approximation method is found to outperform the existing ones in terms of estimation accuracies, tracking range, computation complexity, and convergence speed. As expected, our second order approximation method provides an even further improvement at the expense of higher computation complication.[[notice]]補正完畢[[journaltype]]國外[[incitationindex]]SCI[[booktype]]紙本[[booktype]]電子版[[countrycodes]]DE

Carbonic anhydrase XII is a marker of good prognosis in invasive breast carcinoma

Hypoxia and pH influence gene expression in tumours, and it is becoming increasingly clear that the pattern of genes expressed by a tumour determines its growth and survival characteristics. Hypoxia-inducible factor-1 (HIF-1) is a key mediator of the cellular response to hypoxia and high HIF-1 expression has been identified as a poor prognostic factor in tumours. Recently, we identified the tumour-associated carbonic anhydrases (CA), CA9 and CA12 as hypoxia-inducible in tumour cell lines. Furthermore, we identified CA IX to be a poor prognostic factor in breast cancer. The aim of this study was to assess the prognostic significance of CA XII. CA XII expression was studied by immunohistochemistry in a series of 103 cases of invasive breast cancer and any association with recognised prognostic factors or relation with the outcome was examined. CA XII expression was present in 77 out of 103 (75%) cases and was associated with lower grade (P=0.001), positive estrogen receptor status (P&lt;0.001), and negative epidermal growth factor receptor status (P&lt;0.001). Furthermore, although CA XII expression was associated with an absence of necrosis (P&lt;0.001), expression of CA XII in some high-grade tumours was induced in regions directly adjacent to morphological necrosis. Additionally, using univariate analysis, CA XII positive tumours were associated with a lower relapse rate (P=0.04) and a better overall survival (P=0.01). In conclusion, CA XII expression is influenced both by factors related to differentiation and hypoxia in breast cancer in vivo and CA XII expression is associated with a better prognosis in an unselected series of invasive breast carcinoma patients

Demographic and spatial predictors of anemia in women of reproductive age in Timor-Leste: Implications for health program prioritization

10.1371/journal.pone.0091252PLoS ONE93-POLN

The prolyl hydroxylase enzymes are positively associated with hypoxia-inducible factor-1α and vascular endothelial growth factor in human breast cancer and alter in response to primary systemic treatment with epirubicin and tamoxifen

Introduction: The purpose of the present study was to investigate the relationship of expression of hypoxia inducible factor (HIF)-1α-modifying enzymes prolyl hydroxylase (PHD)1, PHD2 and PHD3 to response of tumours and survival in breast cancer patients enrolled in a phase II trial of neoadjuvant anthracycline and tamoxifen therapy.Methods: The expression of PHD1, PHD2 and PHD3 together with HIF-1α and the HIF-inducible genes vascular endothelial cell growth factor (VEGF) and carbonic anhydrase IX were assessed by immunohistochemistry using a tissue microarray approach in 211 patients with T2-4 N0-1 breast cancer enrolled in a randomised trial comparing single-agent epirubicin versus epirubicin and tamoxifen as the primary systemic treatment.Results: PHD1, PHD2 and PHD3 were detected in 47/179 (26.7%), 85/163 (52.2%) and 69/177 (39%) of tumours at baseline. PHD2 and PHD3 expression was moderate/strong whereas PHD1 expression was generally weak. There was a significant positive correlation between HIF-1α and PHD1 (P = 0.002) and PHD3 (P &lt; 0.05) but not PHD2 (P = 0.41). There was a significant positive relationship between VEGF and PHD1 (P &lt; 0.008) and PHD3 (P = 0.001) but not PHD2 (P = 0.09). PHD1, PHD2 and PHD3 expression was significantly increased after epirubicin therapy (all P &lt; 0.000) with no significant difference in PHD changes between the treatment arms. There was no significant difference in response in tumours that expressed PHDs and PHD expression was not associated with survival.Conclusions: Although expression of the PHDs was not related to response or survival in patients receiving neoadjuvant epirubicin, our data provide the first evidence that these enzymes are upregulated on therapy in breast cancer and that the biological effects independent of HIF make them therapeutic targets. © 2011 Fox et al.; licensee BioMed Central Ltd

Trends and predictions of metabolic risk factors for acute myocardial infarction: findings from a multiethnic nationwide cohort

BACKGROUND: Understanding the trajectories of metabolic risk factors for acute myocardial infarction (AMI) is necessary for healthcare policymaking. We estimated future projections of the incidence of metabolic diseases in a multi-ethnic population with AMI. METHODS: The incidence and mortality contributed by metabolic risk factors in the population with AMI (diabetes mellitus [T2DM], hypertension, hyperlipidemia, overweight/obesity, active/previous smokers) were projected up to year 2050, using linear and Poisson regression models based on the Singapore Myocardial Infarction Registry from 2007 to 2018. Forecast analysis was stratified based on age, sex and ethnicity. FINDINGS: From 2025 to 2050, the incidence of AMI is predicted to rise by 194.4% from 482 to 1418 per 100,000 population. The largest percentage increase in metabolic risk factors within the population with AMI is projected to be overweight/obesity (880.0% increase), followed by hypertension (248.7% increase), T2DM (215.7% increase), hyperlipidemia (205.0% increase), and active/previous smoking (164.8% increase). The number of AMI-related deaths is expected to increase by 294.7% in individuals with overweight/obesity, while mortality is predicted to decrease by 11.7% in hyperlipidemia, 29.9% in hypertension, 32.7% in T2DM and 49.6% in active/previous smokers, from 2025 to 2050. Compared with Chinese individuals, Indian and Malay individuals bear a disproportionate burden of overweight/obesity incidence and AMI-related mortality. INTERPRETATION: The incidence of AMI is projected to continue rising in the coming decades. Overweight/obesity will emerge as fastest-growing metabolic risk factor and the leading risk factor for AMI-related mortality. FUNDING: This research was supported by the NUHS Seed Fund (NUHSRO/2022/058/RO5+6/Seed-Mar/03) and National Medical Research Council Research Training Fellowship (MOH-001131). The SMIR is a national, ministry-funded registry run by the National Registry of Diseases Office and funded by the Ministry of Health, Singapore