Miracle-dz/UniFAR-FTUs huggingface dataset:
Imidazoline Receptors but Not α2-Adrenoceptors Are Regulated in Spontaneously Hypertensive Rat Heart by Chronic Moxonidine Treatment

We have recently identified imidazoline I1-receptors in the heart. In the present study, we tested regulation of cardiac I1-receptors versus α2 -adrenoceptors in response to hypertension and to chronic exposure to agonist. Spontaneously hypertensive rats (SHR, 12–14 weeks old) received moxonidine (10, 60, and 120 μg/kg/h s.c.) for 1 and 4 weeks. Autoradiographic binding of 125I-paraiodoclonidine (0.5 nM, 1 h, 22°C) and inhibition of binding with epinephrine (10–10–10–5 M) demonstrated the presence of α2-adrenoceptors in heart atria and ventricles. Immunoblotting and reverse transcription-polymerase chain reaction identified α2A-α2B-, and α2C, and -adrenoceptor proteins and mRNA, respectively. However, compared with normotensive controls, cardiac α2 -adrenoceptor kinetic parameters, receptor proteins, and mRNAs were not altered in SHR with or without moxonidine treatment. In contrast, autoradiography showed that up-regulated atrial I1-receptors in SHR are dose-dependently normalized by 1 week, with no additional effect after 4 weeks of treatment. Moxonidine (120 μg/kg/h) decreased Bmax in right (40.0 ± 2.9–7.0 ± 0.6 fmol/unit area; p < 0.01) and left (27.7 ± 2.8–7.1 ± 0.4 fmol/unit area; p < 0.01) atria, and decreased the 85- and 29-kDa imidazoline receptor protein bands, in right atria, to 51.8 ± 3.0% (p < 0.01) and 82.7 ± 5.2% (p < 0.03) of vehicle-treated SHR, respectively. Moxonidine-associated percentage of decrease in Bmax only correlated with the 85-kDa protein (R2 = 0.57; p < 0.006), suggesting that this protein may represent I2-receptors. The weak but significant correlation between the two imidazoline receptor proteins (R2 = 0.28; p < 0.03) implies that they arise from the same gene. In conclusion, the heart possesses I1-receptors and α2-adrenoceptors, but only I1-receptors are responsive to hypertension and to chronic in vivo treatment with a selective I1-receptor agonist.
Normal-repeat-length polyglutamine peptides accelerate aggregation nucleation and cytotoxicity of expanded polyglutamine proteins

The dependence of disease risk and age-of-onset on expanded CAG repeat length in diseases like Huntington's disease (HD) is well established and correlates with the repeat-length-dependent nucleation kinetics of polyglutamine (polyGln) aggregation. The wide variation in ages of onset among patients with the same repeat length, however, suggests a role for modifying factors. Here we describe the ability of normal-length polyGln repeat sequences to greatly accelerate the nucleation kinetics of an expanded polyGln peptide. We find that normal-length polyGln peptides enhance the in vitro nucleation kinetics of a Q47 peptide in a concentration-dependent and repeat-length-dependent manner. In vivo, we show that coexpression of a Q20 sequence in a Drosophila model of HD expressing Htt exon 1 protein with an Q93 repeat accelerates both aggregate formation and neurotoxicity. The accelerating effect of short polyGln peptides is attributable to the promiscuity of polyGln aggregate elongation and reflects the intimate relationship between nucleus formation and early elongation events in establishing nucleation kinetics. The results suggest that the overall state of the polyGln protein network in a cellular environment may have a profound effect on the toxic consequences of polyGln expansion and thus may serve as a genetic modifier of age of onset in HD.
State-Dependent Choice Model for TV Programs with Externality: Analysis of Viewing Behavior

This study analyzes TV program content for viewers with respect to the following three properties: primary utility (intrinsic value by genre, cast, and so on), macro externality, such as the effect of others' past behavior (audience ratings), and state dependence, or the viewer's past actions that determine whether to watch the program. Focusing on the effects of macro externality and state-dependence on viewer behavior, the authors construct a hierarchical Bayesian model and derive an individual utility function. Applying their method to the choice of TV programs in Japan, they estimate the effects of macro externality and state dependence on an individual's viewing behavior, and illustrate the distribution of these effects. The authors find that macro externality has a strong overall effect on the total number of viewers and the state-dependence effect has a slightly positive effect. Moreover, comparing the attributes revealed that male viewers tend to show a lower effect of ratings and higher state dependence than females. They find that the older the viewers are, the higher the effect of state dependence. Further, using utility function data obtained by our estimation, they conduct a simulation to measure the dynamic effects of macro externality and state dependence.
Another Look at Mutual Fund Performance

Recent studies of mutual funds have all arrived at the same conclusion: mutual fund performance has been inferior to the performance of the market indices. One of the most prominent of these studies was conducted by William F. Sharpe. He showed that if his measure of mutual fund performance, the reward-to-variability ratio, is calculated net of management expenses for each fund in his sample of thirty-four, then the average value of this ratio over the thirty-four funds is significantly less than the same measure applied to the Dow Jones Industrials over the 1954–1963 period. From this evidence, Sharpe concluded that average mutual fund performance was distinctly inferior to an investment in the Dow Jones Industrial Average. It is the intent of this paper to show that if another variable, namely the third moment of the fund's annual rate of return, is introduced into the investor's decision process, Sharpe's conclusion must be altered.
A multicommodity model of futures prices: Using futures prices of one commodity to estimate the stochastic process of another

This article proposes a multicommodity model of futures prices of more than one commodity that allows the use of long‐maturity futures prices available for one commodity to estimate futures prices for the other. The model considers that commodity prices have common and commodity‐specific factors. A procedure for choosing the number of both types of unobservable‐Gaussian factors is presented. Also, it is shown how commodities with and without seasonality may be jointly modeled and how to estimate the model using Kalman filter. Results for the West Texas Intermediate–Brent and for the West Texas Intermediate–unleaded gasoline models presented show strong improvements over the traditional individual‐commodity models, with much lower out‐of‐sample errors and better volatility estimates, even when using fewer factors. © 2008 Wiley Periodicals, Inc. Jrl Fut Mark 28:537–560, 2008
Use of the lung flute for sputum induction in children with cystic fibrosis: A pilot study

This study aimed to assess the effectiveness of the Lung Flute in obtaining a sputum sample from children with cystic fibrosis (CF) that were not productive of sputum with coughing alone. Children attending an outpatient CF clinic who were not able to provide a sample with coughing alone were eligible. Each child used the Lung Flute on two occasions at least one month apart. The primary outcome was expectoration of a sputum sample. Secondary outcomes were sputum microbiology, time taken for the procedure, and ease of use of the device as assessed by the patient using a visual analogue scale (VAS), with 0/10 representing very easy and 10/10 representing very hard. Twenty‐five children participated (15 males, mean age 12.7 range 6.5–17.9). Overall, a sputum sample was obtained on 26/50 (52%) uses of the device. In children that presented with a moist cough, a sample was obtained on 17/17 (100%) occasions, compared to 9/33 (27%) occasions when a child presented with a dry cough. A positive culture result for at least one known CF pathogen was found in 24/26 samples. Culture results from obtained samples resulted in management changes in 12 cases. Mean time taken to obtain a sample was 9.8 min (SD 2.2). Mean ease of use on the VAS was 1.5 (SD 1.6). Conclusion: The lung flute appears to be a clinically useful and easy device for sputum induction in children with CF. Further research comparing its effectiveness to other sputum induction methods is warranted. Pediatr Pulmonol. 2015; 50:340–343. © 2014 Wiley Periodicals, Inc.
Estimating Activity Costs: How the Provision of Accurate Historical Activity Data from a Biased Cost System Can Improve Individuals' Cost Estimation Accuracy

An integral component of effective cost control and performance evaluation is the ability to accurately estimate relationships between activities and overhead costs (i.e., activity costs). Individuals using a single cost pool system often have to rely on memory of historical activity data when estimating activity costs. If individuals' recall of data is representative of the historical data, then reliance on memory should not be detrimental to cost estimation accuracy. However, individuals often possess incorrect initial beliefs about activity costs. These incorrect beliefs are expected to serve as an anchor from which individuals make insufficient adjustments when estimating activity costs based on memory of historical activity data. Multiple cost pool systems frequently provide biased standard rates; however, such systems also provide accurate historical activity data when individuals estimate costs. I extend prior accounting research by experimentally examining whether a multiple cost pool system's pro.
HIV-2 Antiviral Potency and Selection of Drug Resistance Mutations by the Integrase Strand Transfer Inhibitor Elvitegravir and NRTIs Emtricitabine and Tenofovir In Vitro

Background:HIV-2 is susceptible to only a subset of approved antiretroviral drugs. A single tablet regimen containing the integrase strand transfer inhibitor elvitegravir (EVG) boosted by cobicistat plus the nucleoside reverse transcriptase (RT) inhibitors emtricitabine (FTC) and tenofovir disoproxil fumarate (EVG/COBI/FTC/TDF) has potent activity against HIV-1 and may have utility against HIV-2. Methods:HIV-2 susceptibility to EVG, FTC, and tenofovir (TFV) and selection of resistance mutations were characterized in vitro using dose escalation and breakthrough methods. HIV-2 containing the selected mutations was constructed and phenotyped in vitro. Results:The inhibitors EVG, FTC, and TFV had potent activity against HIV-2 with EC50 values of 1.6 nM, 0.99 &mgr;M, and 3.5 &mgr;M, respectively. In resistance selections, EVG selected E92G/Q and S147N in integrase, FTC selected M184V/I in RT, and TFV selected K65R and Y115F in RT. HIV-2 site-directed mutant (SDM) viruses with E92G and E92Q integrase mutations showed 3.7- and 16-fold reduced susceptibilities to EVG, respectively. The RT M184I and M184V SDM viruses were both highly resistant to FTC (34- and >1000-fold, respectively). The RT K65R SDM virus had 2.2- and 9.1-fold reduced susceptibilities to TFV and FTC, respectively, and the addition of Y115F to K65R further decreased susceptibility to both drugs. Conclusions:The antiretrovirals EVG, FTC, and TFV showed potent inhibition of HIV-1 and HIV-2 in vitro and selected analogous mutations in HIV-2 and HIV-1. This suggests that the single tablet regimen of EVG/COBI/FTC/TDF should be studied as a treatment option for HIV-2 infection and would likely select for known resistance mutations.
Chained Cascade Network for Object Detection

Cascade is a widely used approach that rejects obvious negative samples at early stages for learning better classifier and faster inference. This paper presents chained cascade network (CC-Net). In this CC-Net, there are many cascade stages. Preceding cascade stages are placed at shallow layers. Easy hard examples are rejected at shallow layers so that the computation for deeper or wider layers is not required. In this way, features and classifiers at latter stages handle more difficult samples with the help of features and classifiers in previous stages. It yields consistent boost in detection performance on PASCAL VOC 2007 and ImageNet for both fast RCNN and Faster RCNN. CC-Net saves computation for both training and testing. Code is available on https://github.com/wk910930/ccnn.
The Production Responses of the Competitive Firm to Three Conventional Distributional Shifts: A Unified Perspective

This paper presents a unified perspective on the production responses of the competitive firm to three conventional distributional shifts: (i) a rightward shift of the distribution, (ii) a Rothschild-Stiglitz increase in risk, and (iii) a Menezes et al. increase in downside risk. In particular, assuming that the von Neumann-Morgenstern utility is increasing and concave, and assuming its higher-order derivatives are uniformly signed, we demonstrate that the production responses are unambiguous in the case of price less than or equal to marginal cost. In the alternative case of price greater than marginal cost, we then demonstrate that the production responses can be signed unambiguously by reference to sufficient conditions motivated by absolute risk aversion and by absolute prudence.
Identification of Hypertension-Susceptibility Genes and Pathways by a Systemic Multiple Candidate Gene Approach: The Millennium Genome Project for Hypertension

A multiple candidate-gene approach was used to investigate not only candidate genes, but also candidate pathways involved in the regulation of blood pressure. We evaluated 307 single nucleotide polymorphisms (SNPs) in 307 genes and performed an association study between 758 cases and 726 controls. Genes were selected from among those encoding components of signal transduction pathways, including receptors, soluble carrier proteins, binding proteins, channels, enzymes, and G-proteins, that are potentially related to blood pressure regulation. In total, 38 SNPs were positively (p<0.05) associated with hypertension. Replication of the findings and possible polygenic interaction was evaluated in five G-protein–related positive genes (GNI2, GNA14, RGS2, RGS19, RGS20) in a large cohort population (total n=9,700, 3,305 hypertensives and 3,827 normotensive controls). In RGS20 and GNA14, dominant models for the minor allele were significantly associated with hypertension. Multiple dimension reduction (MDR) analysis revealed the presence of gene–gene interaction between GNA14 and RGS20. The MDR-proved combination of two genotypes showed a significant association with hypertension (χ2=9.93, p=0.0016) with an odds ratio of the high-risk genotype of 1.168 (95% confidence interval [CI] [1.061–1.287]). After correction for all possible confounding parameters, the MDR-proved high-risk genotype was still a risk for hypertension (p=0.0052). Furthermore, the high-risk genotype was associated with a significantly higher systolic blood pressure (133.08±19.46 vs. 132.25±19.19 mmHg, p=0.04) and diastolic blood pressure (79.65±11.49 vs. 79.01±11.32 mmHg, p=0.019) in the total population. In conclusion, a systemic multiple candidate gene approach can be used to identify not only hypertension-susceptibility genes but also hypertension-susceptibility pathways in which related genes may synergistically collaborate through gene–gene interactions to predispose to hypertension.
Regional impervious surface estimation: an urban heat island application

This paper describes a GIS-based estimation method that can be used to forecast future amounts of impervious surface as a mitigation measure for urban heat island effect in a metropolitan region. The method is unique because it employs a regression model that links the existing amount of impervious surface to population and employment at the census tract level. This approach provides a means to forecast future amounts of impervious surface based on projected population and employment. The method also includes a detailed analysis of high-resolution aerial photography to divide impervious surfaces into different categories. Subdividing impervious surfaces is necessary to evaluate potential urban heat island mitigation policies for different types of impervious surface. The analysis here shows that the impervious surface in the metropolitan Atlanta region will increase to 2638 km2 in 2030, an increase of 45% from 2000. The most common type of impervious surface is dark-coloured pavement. Within this study area, the analyses showed that two-thirds of impervious surfaces are dark. Replacing dark pavement with light pavement materials, therefore, represents an important opportunity to mitigate the urban heat island effect in the Atlanta region.
Database-as-a-Service for Big Data: An Overview

The last two decades were marked by an exponential growth in the volume of data originating from various data sources, from mobile phones to social media contents, all through the multitude devices of the Internet of Things. This flow of data can’t be managed using a classical approach and has led to the emergence of a new buzz word: Big Data. Among the research challenges related to Big Data there is the issue of data storage. Traditional relational database systems proved to be unable to efficiently manage Big Data datasets. In this context, Cloud Computing plays a relevant role, as it offers interesting models to deal with Big Data storage, especially the model known as Database as a Service (DBaaS). We propose, in this article, a review of database solutions that are offered as DBaaS and discuss their adaptability to Big Data applications.
Reduced-Order Models for Representing Converters in Power System Studies

A reduced-order model that preserves physical meaning is important for generating insight in large-scale power system studies. The conventional model-order reduction for a multiple-timescale system is based on discarding states with fast (short timescale) dynamics. It has been successfully applied to synchronous machines, but is inaccurate when applied to power converters because the timescales of fast and slow states are not sufficiently separated. In the method proposed here, several fast states are at first discarded but a representation of their interaction with the slow states is added back. Recognizing that the fast states of many converters are linear allows well-developed linear system theories to be used to implement this concept. All the information of the original system relevant to system-wide dynamics, including nonlinearity, is preserved, which facilitates judgments on system stability and insight into control design. The method is tested on a converter-supplied mini power system and the comparison of analytical and experiment results confirms high preciseness in a broad range of conditions.
Implications of acquired oxacillin resistance in the management and control of Staphylococcus aureus infections.

Refinements in testing for resistance to penicillinase-resistant penicillins (PRP) in Staphylococcus aureus have resulted in confusion in classifying isolates as PRP susceptible or resistant. Specifically, a group of organisms has been identified that produce large amounts of beta-lactamase and appear borderline resistant. These organisms have been called "occult resistant" or "acquired oxacillin-resistant" S. aureus (AORSA). A retrospective study was conducted to evaluate the implication of this in vitro phenomenon in managing patients with AORSA infections. Among 134 patients with S. aureus infections, 89 were infected with oxacillin-susceptible S. aureus (OSSA), 26 with AORSA, and 19 with oxacillin-resistant S. aureus (ORSA). There were no significant differences in outcomes when OSSA and AORSA infections were treated with PRP (chi 2MH = .990; P = .32). These results do not suppor the contention that AORSA infections should be managed differently from OSSA infections. Identifying AORSA may not be helpful in guiding antimicrobial therapy or predicting the outcome of infections with AORSA.
Updates in Antiplatelet Agents Used in Cardiovascular Diseases

Background: Antiplatelet therapy is a cornerstone in coronary artery disease management. However, patients with acute coronary syndrome still remain at risk of recurrent cardiovascular events despite the advance of medical therapy. Objective: This article provides a review of antiplatelet agents used in cardiovascular diseases and focus on updates in the past 5 years. Method: Peer-reviewed clinical trials and relevant treatment guidelines were identified from MEDLINE and Current Content database (from 1966 to April 15, 2013) using search terms aspirin, clopidogrel, prasugrel, ticagrelor, glycoprotein IIb/IIIa inhibitors, antiplatelet agents, coronary artery disease, acute coronary syndrome, pharmacology, pharmacokinetics, and pharmacodynamics. Citations from the available articles were also reviewed for additional references. Results: In unstable angina and non-ST-segment elevation myocardial infarction (MI), dual antiplatelet therapy (aspirin and clopidogrel) demonstrated a reduction in death from cardiovascular causes, nonfatal MI, or stroke (relative risk 0.80; 95% confidence interval [CI], 0.72-0.90). In ST-segment elevation MI, dual antiplatelet therapy reduced the rate of occluded infarct-related artery/death or recurrent MI (95% CI, 24%-47%). Newer agents such as prasugrel, when compared to clopidogrel, reduced death from vascular causes, MI, or stroke in patients undergoing percutaneous coronary intervention (PCI; hazard ratio [HR], 0.81; 95% CI 0.73-0.90) but not in those receiving medical management only. When compared to clopidogrel, ticagrelor reduces death from vascular causes, MI, or stroke (HR: 0.84; 95% CI, 0.77-0.92) in patients undergoing PCI or receiving medical management only. Both the agents, however, increase the risk of bleeding in certain patient population. Conclusions: In the last 5 years, newer antiplatelet agents, including prasugrel and ticagrelor, have been demonstrated to reduce recurrent cardiovascular events compared to standard therapy and, however, also caused increase bleeding in selected patient populations. Newer agents including shorter acting P2Y12 inhibitor or antiplatelets that target other receptors are being evaluated to improve/maintain therapeutic efficacy yet minimize the risk of bleeding.
A corporate system for continuous innovation: the case of Google Inc.

Purpose – History is full of companies that were once innovative leaders but lost their innovative ability. The purpose of this paper is to explore, from a firm‐level perspective, organizational characteristics for continuous innovation in rapidly changing industries.Design/methodology/approach – Findings from 28 interviews at Google Inc., are compared to previous research on organizational characteristics for continuous innovation.Findings – Google's organization can be viewed as a dynamic and open corporate system for continuous innovation, involving the entire organization and supported by an innovation‐oriented and change‐prone top management and board. The relative importance of eight organizational characteristics in this corporate system is elaborated upon.Research limitations/implications – There is a need for empirical research contributing to the development of a more comprehensive analytical framework for continuous innovation, including the role of culture and selection/facilitation of self‐or.