Miracle-dz/UniFAR-FTUs huggingface dataset:
Expression of plasma membrane GABA transporters but not of the vesicular GABA transporter in dentate granule cells after kainic acid seizures

Kainic acid‐induced seizures cause a marked increase in the expression of glutamate decarboxylase 67 (GAD67) in granule cells of the dentate gyrus. To determine the possible modes of sequestration of newly formed γ‐aminobutyric acid (GABA), we used in situ hybridization and immunocytochemistry to investigate the expression of several proteins related to GABA in dentate granule cells of rats 4 h to 60 days after kainic acid‐induced status epilepticus and in controls. GAD67 and GAD65 mRNA levels were increased by up to 300% and 800%, respectively, in the granule cell layer 6–24 h after kainate injection. Subsequently, increased GAD and GABA immunoreactivity was observed in the terminal field of mossy fibers and in presumed dendrites of granule cells. mRNA of both known plasma membrane GABA transporters (GAT‐1 and GAT‐3) was expressed in granule cells of control rats. GAT‐1 mRNA levels increased (by 30%) 9 h after kainate injection but were reduced by about 25% at later intervals. GAT‐3 mRNA was reduced (by 35–75%) in granule cells 4 h to 30 days after kainic acid injection. In contrast, no expression of the mRNA or immunoreactivity of the vesicular GABA transporter was detected in granule cells or in mossy fibers, respectively. GABA transaminase mRNA was only faintly expressed in granule cells, and its levels were reduced (by 60–65%) 12 h to 30 days after kainate treatment. The results indicate that GABA can be taken up and synthesized in granule cells. No evidence for the expression of the vesicular GABA transporter (VGAT) in granule cells was obtained. After sustained epileptic seizures, the markedly increased expression of glutamate decarboxylase and the reduced expression of GABA transaminase may result in increased cytoplasmic GABA concentrations in granule cells. It is suggested that, during epileptic seizures, elevated intracellular GABA and sodium concentration could then result in nonvesicular release of GABA from granule cell dendrites. GABA could then act on GABA‐A receptors, protecting granule cells from overexcitation. © 2003 Wiley‐Liss, Inc.
Essays in Housing Markets and Financial Fragility

This dissertation is motivated by the housing crisis of 2008. It consists of three chapters. In the first chapter, "Too Much Skin-in-the-Game? The Effect of Mortgage Market Concentration on Credit and House Prices," I propose a new theory to help explain the housing crisis. During the housing boom, a small number of institutions the government-sponsored enterprises (GSEs) and a few banks held most of U.S. mortgage risk. I develop a theory in which such concentration of mortgage exposure can explain features of the housing crisis. I show that large lenders with many outstanding mortgages have incentives to extend risky credit to prop up house prices. An increase in concentration can lead to a boom with worsening credit quality and a subsequent bust with widespread defaults. In the second chapter, "Concentration and Lending in Mortgage Markets," joint with Ronel Elul and David Musto, we attempt to test the theory described in the first chapter. We provide evidence that concentration in mortgage markets can create perverse lending incentives. We exploit variation in the size of the GSEs' outstanding mortgage exposure across MSAs. Using a loan-level dataset, we provide evidence that the GSEs were more likely to engage in high-risk activities in areas where they had a large exposure to outstanding mortgages. We also provide evidence that this relationship is driven by an incentive to keep house prices high. In the final chapter, "Housing Booms and the Crowding-Out Effect," joint with Itay Goldstein, we study the effect that investment in real estate assets has on the economy. We develop a theory in which housing price booms can sometimes lead to a crowding-out of corporate investment. We show that an increase in real estate prices does not necessarily increase aggregate investment even when firms actively use real estate assets as collateral to borrow against and invest the proceeds in positive NPV projects. We argue that at times, it can be optimal to decrease the price of housing rather than to support high housing prices to stimulate the economy and characterize when this is the case. Degree Type Dissertation Degree Name Doctor of Philosophy (PhD) Graduate Group Finance First Advisor Itay Glodstein Second Advisor Vincent Glode
Effects of Resveratrol on Endothelial Progenitor Cells and Their Contributions to Reendothelialization in Intima-injured Rats

The aim of this study was to investigate the effects of resveratrol on endothelial progenitor cell (EPC) activities in vitro and on the mobilization of circulating EPCs, and reendothelialization in balloon-injured aorta of rats. After being isolated, cultured, and characterized, human EPCs were stimulated with resveratrol. We found that a low concentration of resveratrol (1 μM) led to significant enhanced activities of proliferation, migration, and adhesion, as well as promoting endothelial nitric acid synthetase (eNOS) expression in EPCs, whereas a high concentration (60 μM) inhibited the aforementioned functions and eNOS expression. In a rat model of injured aorta, a low dosage of resveratrol (10 mg/kg) increased the amount of EPCs in rat circulation as compared with placebo, whereas the result of a high dosage (50 mg/kg) did not reach statistical difference. In addition, 10 mg/kg of resveratrol both accelerated reendothelialization and inhibited neointimal formation; however, 50 mg/kg only reduced neointimal formation, which was not as effective as the previous one. eNOS expression in injured arteries was potently enhanced in the 10 mg/kg group, but not in the 50 mg/kg group.These findings suggest that a low dosage of resveratrol could markedly raise the proliferative, migrative, and adhesive activities of EPCs and upgrade eNOS expression in vitro as well as increase EPC mobilization, enhance eNOS expression, and accelerate the repair of injured artery; however, a high dosage cannot.
Estimating Promotion Effects Using Big Data: A Partially Profiled LASSO Model With Endogeneity Correction

Retailers are interested in understanding which price promotions are profitable and which are not. However, simultaneously estimating the promotion effects of a large number of products on retailer sales and profits is technically challenging for both researchers and practitioners. To address this challenge, this study proposes a Partially Profiled Least Absolute Shrinkage and Selection Operator (Partially Profiled LASSO) model, which can estimate ultra-high-dimensional regression relationships at a low computational cost and control for the endogeneity of promotion depth. The model can flexibly incorporate the time-varying promotion effects and the cross-over effects among the promotions of different products. We conduct an empirical study using data provided by a large retailer over a five-month period. Our model efficiently identifies products with promotion effects and the promotion effects are significantly associated with certain promotion, product, and category characteristics. The results also show that our model with cross-over effects outperforms the benchmark models that are widely used to handle the high-dimensional predictor matrix (e.g., the standard LASSO and principal component regression methods). This paper contributes to the related literature on price promotion and marketing analytics in data-rich environments, and provides implications for retailers to make more informed promotion strategies.
Cost-effectiveness of primary screening for CKD: a systematic review.

BACKGROUND Chronic kidney disease (CKD) is a major health problem with an increasing incidence worldwide. Data on the cost-effectiveness of CKD screening in the general population have been conflicting. STUDY DESIGN Systematic review. SETTING & POPULATION General, hypertensive, and diabetic populations. No restriction on setting. SELECTION CRITERIA FOR STUDIES Studies that evaluated the cost-effectiveness of screening for CKD. INTERVENTION Screening for CKD by proteinuria or estimated glomerular filtration rate (eGFR). OUTCOMES Incremental cost-effectiveness ratio of screening by proteinuria or eGFR compared with either no screening or usual care. RESULTS 9 studies met criteria for inclusion. 8 studies evaluated the cost-effectiveness of proteinuria screening and 2 evaluated screening with eGFR. For proteinuria screening, incremental cost-effectiveness ratios ranged from $14,063-$160,018/quality-adjusted life-year (QALY) in the general population, $5,298-$54,943/QALY in the diabetic population, and $23,028-$73,939/QALY in the hypertensive population. For eGFR screening, one study reported a cost of $23,680/QALY in the diabetic population and the range across the 2 studies was $100,253-$109,912/QALY in the general population. The incidence of CKD, rate of progression, and effectiveness of drug therapy were major drivers of cost-effectiveness. LIMITATIONS Few studies evaluated screening by eGFR. Performance of a quantitative meta-analysis on influential assumptions was not conducted because of few available studies and heterogeneity in model designs. CONCLUSIONS Screening for CKD is suggested to be cost-effective in patients with diabetes and hypertension. CKD screening may be cost-effective in populations with higher incidences of CKD, rapid rates of progression, and more effective drug therapy.
Regional Anti-Corruption and CSR Disclosure in a Transition Economy: The Contingent Effects of Ownership and Political Connection

Based on the empirical data of China’s Shanghai and Shenzhen A-share market, this paper examined the impact of regional anti-corruption intensity on corporate social responsibility (CSR) disclosure. The results indicate that (1) regional anti-corruption intensity has a significant positive effect on firms’ CSR disclosure; (2) through the grouping test based on the ownership of firms, it was found that the positive effect of anti-corruption intensity on CSR disclosure in the sample of non-state-owned enterprises was more significant and positive than that of state-owned enterprises (SOEs); and (3) through the grouping test of whether or not the enterprises had political connections, the positive effect of regional anti-corruption intensity on CSR disclosure was stronger and more significant in firms with political connections (relative to those with no or weak political connections). This paper sheds light on the research into anti-corruption policies by linking government macro policy and enterprises’ micro social economic behaviors, and it provides empirical evidence for this linkage. This paper also contributes to organizational legitimacy theory and CSR theory by probing the impact of anti-corruption policies on firms’ CSR disclosure. At the same time, the effects of two contingency factors (ownership and political connection) also provide some practical implications to the relevant government departments by: (1) speeding up the market-oriented reform of state-owned enterprises including clarifying the boundaries of authority and responsibility between SOEs and the government, and conducting the de-administration of managers of SOEs; and (2) encouraging firms to focus on market competition and be more socially responsible, instead of speculating with political rents.
An iISS Framework for Stochastic Robustness of Interconnected Nonlinear Systems

This paper addresses integral input-to-state stability (iISS) for stochastic nonlinear dynamical systems and develops Lyapunov-type criteria. The developments offer an iISS small-gain framework for verifying robustness of interconnected systems with respect to disturbances. The framework not only includes input-to-state stability (ISS) as a special case, but also highlights fundamental differences between the stochastic and deterministic systems. In particular, dealing with nonlinearities in interconnection gives rise to a unique issue of degradation in the presence of stochastic noises. This paper addresses this issue by coping judiciously with the effect of the gradient of Lyapunov functions of subsystems through diffusion fields in composing a Lyapunov function of the entire system. This paper employs two types of robustness notions, and demonstrates that the influence of the stochastic degradation on one notion is considerably different from the influence on the other notion in dealing with interconnected systems.
Mortality in obstructive sleep apnea-hypopnea patients treated with positive airway pressure.

STUDY OBJECTIVES The aims of this study were to analyze mortality in patients with obstructive sleep apnea-hypopnea syndrome (OSAHS) treated with positive airway pressure (PAP) and to know whether PAP compliance affects survival, as well as to investigate the prognostic value of several pretreatment variables. DESIGN AND PATIENTS A study was made of an historical cohort of 871 patients in whom OSAHS had been diagnosed by sleep study between January 1994 and December 2000 and who had been treated with PAP. Patients were followed up until December 2001. The mean (+/- SD) age of the group was 55.4 +/- 10.6 years, the mean apnea-hypopnea index (AHI) 55.1 +/- 28.7, and 80.9% were men. To assess whether mortality was influenced by PAP therapy compliance, patients were assigned to one of the following compliance categories: < 1 h/d; 1 to 6 h/d; or > 6 h/d. Survival rates were calculated according to the Kaplan-Meier method. Survival curves were compared with the log-rank test and the trend test, when necessary. Univariate and multivariate analyses using a time-dependent Cox model were performed to elicit which variables correlated with mortality. SETTING Outpatient sleep disorders unit. RESULTS By the end of the follow-up period (mean duration, 48.5 +/- 22.7 months), 46 patients had died. The 5-year cumulative survival rates were significantly lower in patients who did not use PAP (compliance < 1 h) than in those who used the device for > 6 h/d (85.5% [95% confidence interval (CI), 0.78 to 0.92] vs 96.4% [95% CI, 0.94 to 0.98; p < 0.00005]) and 1 to 6 h/d (85.5% [95% CI, 0.78 to 0.92] vs 91.3% [ 95% CI, 0.88 to 0.94; p = 0.01]), respectively. A trend in survival rates across the groups was identified (p = 0.0004). The main cause of death in 19 cases was cardiovascular disease (CVD). Variables that independently correlated with mortality in the multivariate analysis were the following PAP use categories: compliance for > 6 h/d (odds ratio [OR], 0.10; 95% CI, 0.04 to 0.29); compliance for 1 to 6 h/d (OR, 0.28; 95% CI, 0.11 to 0.69); arterial hypertension (AHT) [OR, 3.25; 95% CI, 1.24 to 8.54]; age (OR, 1.06; 95% CI, 1.01 to 1.10); and FEV1 percent predicted (OR, 0.96; 95% CI, 0.94 to 0.98). CONCLUSION Mortality rates in OSAHS patients who did not receive PAP therapy were higher compared with those treated with PAP and were moderately or highly compliant with therapy. A trend in survival across compliance categories was found. Patients died mainly from CVD. Categories of PAP compliance, AHT, age, and FEV1 percent predicted were the variables that independently predicted mortality.
Planning of the internal mammary field based on lymphoscintigraphy localization before postoperative radiotherapy of breast cancer.

BACKGROUND Internal mammary irradiation is still an issue of great debate. Although treatment of internal mammary lymph nodes was routinely given in the majority of randomized trials, data in its value are still limited. The aim of this study is to determine the variability of position of the internal mammary lymph nodes using lymphoscintigraphy and to compare the dose of radiation that reaches these lymph nodes, the heart and lungs if only tangential fields are used. MATERIAL AND METHODS This is a prospective study that included 30 breast cancer patients treated in the department of radiation oncology of the Egyptian National Cancer Institute, Cairo University, planned for postoperative radiotherapy. Lymphoscintigraphy was done for all patients for detection of the exact site of the internal mammary lymph nodes. Dose volume histogram (DVH) was done to measure the dose to the heart using CT planning. Two plans were done for each patient, the first with internal mammary field (plan I), and the second without but with contralateral crossing of the midline by 1cm (plan II). RESULTS The mean percentage of the internal mammary lymph nodes included in the internal mammary field (plan I) was 70.03% while in plan II it was 3.05%. The mean dose percentage reaching the heart in plan I was 54.5% of total dose, while in plan II it was 9.16% of total dose with significant p value<0.001. The mean dose to the heart decreased as the heart volume increased, this significant difference between the 2 plans was maintained for the different heart volumes. Also, the radiation dose to the heart in plan I varied significantly (p: 0.001) between the right side vs the left side with a mean dose of 48.02% and 63.5%, respectively. The mean dose percentage reaching the lungs in plan I and plan II was 46.53% and 24.5% respectively, with significant p value<0.001. CONCLUSION If irradiation of internal mammary chain is intended, then a direct internal mammary field should be used. The planning of internal mammary field should be adjusted according to lymphoscintigraphy so as to include most of the draining internal mammary lymph nodes. The risk of late cardiac and pulmonary complications will increase when using direct internal mammary field, but the risk of cardiac complications will be less in irradiation of right side internal mammary lymph nodes compared to that of irradiation of the left side.
Examination of the immunocontraceptive potential of recombinant rabbit fertilin subunits in rabbit.

Recombinant fertilin subunits produced in a bacterial expression systems were used to test fertilin as an immunocontraceptive antigen in the European rabbit (Oryctolagus cuniculus). Wild female rabbits (n = 40) were immunized with either recombinant rabbit fertilin alpha or beta subunits by the s.c. or intra-Peyer's patch route. High titers of serum anti-fertilin polyclonal IgG antibodies were achieved in all rabbits after repeated boosts, with fertilin-specific IgG but not IgA antibodies detected in vaginal lavages of all animals. The serum IgG antibodies recognized polypeptides in detergent extracts of rabbit sperm with relative molecular masses of 48, 53, and 85 kDa on reducing SDS-PAGE gels and were shown to bind to the head region of methanol-fixed and live caudal rabbit sperm. Preincubation of rabbit sperm with these anti-fertilin IgG antibodies at concentrations of 400 micrograms/ml blocked sperm binding to zona-intact oocytes and inhibited fertilization in vitro by 60-80%. However, despite the levels of circulating and vaginal IgG antibodies achieved, only 4 immunized does failed to become pregnant out of 33 that ovulated. The remaining animals either showed no effect on fertility (n = 29) relative to control animals or failed to ovulate (n = 7). All control animals ovulated and were either fully fertile (n = 15) or were mated to infertile males (n = 4). In addition, proven-fertile male domestic rabbits (n = 3) were immunized s.c. and boosted three times with fertilin beta. Only one animal subsequently showed impaired fertility. These results show that in the rabbit, high levels of circulating sperm-reactive anti-fertilin antibodies and the presence of vaginal IgG does not ensure infertility.
In vitro evaluation and biodistribution of HER2-targeted liposomes loaded with an 125I-labelled DNA-intercalator

Background: Increasing attention is currently focussed on the issue of finding strategies for the delivery of Auger-electron-emitting radionuclides into tumor cell nuclei. Purpose: In this study, we investigated tumor-cell uptake and cell-killing ability in vitro as well as in vivo biodistribution of an 125I-labelled anthracycline derivative administered by means of HER2-targeted liposomes. Methods: Anthracycline derivative Comp1 was radiolabelled with Auger-emitting 125I and encapsulated in liposomes (DSPC:Chol:DSPE-PEG) using pH-gradient loading. Single-chain fragment F5 was anchored to the liposomes as targeting device for HER2. Uptake and specificity of 125I-Comp1 delivered via targeting and non-targeting liposomes were analysed in cultured HER2-overexpressing cells. Cell-killing efficacy was evaluated in SKOV3 cells and biodistribution for up to 48 h was studied after intraperitoneal injection in tumor-bearing female BALB/c nu/nu mice. Results: 125I-Comp1 was specifically taken up by the cultured cells when administered by means of HER2-targeted liposomes and a clear dose-effect correlation in survival of cells was seen with increasing specific activity. The biodistribution studies revealed that 125I-Comp1 accumulated in tumors when distributed using HER2-targeted liposomes and that this effect was absent when using non-targeting liposomes. Conclusion: The HER2-targeted liposomes possess the properties needed to bring about tumor-specific delivery and therapeutic effect of 125I-Comp1.
Perspectives on the future of recycled water in California: results from interviews with water management professionals

Expanded use of recycled water has potential to improve the sustainability of water systems in areas with high water insecurity. Despite this, rates of recycled water use in California remain low. To identify barriers to expansion of recycled water use in California, we conducted open-ended interviews with a targeted sample of 12 stakeholders representing a range of viewpoints among individuals familiar with urban water management operations in California, including experts from government regulatory and public health agencies, wastewater suppliers, independent consultants, and engineers. Barriers identified by respondents related to regulations, infrastructure, funding, technology, health risks, and public perceptions. Respondents provided concrete suggestions for how to lower these barriers and insights into the roles that public health professionals could play in this effort. This work suggests that public health professionals can play a critical role in facilitating the expanded use of recycled water and improving water security and sustainability worldwide.
Where should we apply biochar?

The heating of biomass under low-oxygen conditions generates three co-products, bio-oil, biogas, and biochar. Bio-oil can be stabilized and used as fuel oil or be further refined for various applications and biogas can be used as an energy source during the low-oxygen heating process. Biochar can be used to sequester carbon in soil and has the potential to increase crop yields when it is used to improve yield-limiting soil properties. Complex bio-physical interactions have made it challenging to answer the question of where biochar should be applied for the maximum agronomic and economic benefits. We address this challenge by developing an extensive informatics workflow for processing and analyzing crop yield response data as well as a large spatial-scale modeling platform. We use a probabilistic graphical model to study the relationships between soil and biochar variables and predict the probability and magnitude of crop yield response to biochar application. Our results show an average increase in crop yields ranging from 4.7% to 6.4% depending on the biochar feedstock and application rate. Expected yield increases of at least 6.1% and 8.8% are necessary to cover 25% and 10% of US cropland with biochar. We find that biochar application to crop area with an expected yield increase of at least 5.3%–5.9% would result in carbon sequestration offsetting 0.57%–0.67% of US greenhouse gas emissions. Applying biochar to corn area is the most profitable from a revenue perspective when compared to soybeans and wheat because additional revenues accrued by farmers are not enough to cover the costs of biochar applications in many regions of the United States.