Miracle-dz/UniFAR-FTUs huggingface dataset:
Population Pharmacokinetics of the Selective Serotonin 5-HT1A Receptor Partial Agonist Piclozotan

Background/Aims:Serotonin (5-HT) and its receptors are known to play important roles in various physiological and pathophysiological processes. The 5-HT1A receptor subtype is thought to be involved in psychiatric disorders, immunomodulation, and in cerebral ischemic conditions. Piclozotan, a selective and potent partial agonist of 5-HT1A, has been shown to be neuroprotective against ischemic neuronal damage in animal models. Its pharmacokinetics (PK), tolerability, and safety have been evaluated in patients with acute ischemic stroke. The aim of the study was to describe piclozotan PK, using population PK modeling. Methods:A total of 1308 plasma piclozotan concentration measurements from 84 healthy subjects and 412 plasma piclozotan measurements from 74 stroke patients were included in the analysis. Covariates considered during the model building process included disease status, age, weight, sex, smoking status, and alcohol consumption. Data were analyzed using nonlinear mixed-effects modeling with the NONMEM software system. The final model was qualified via predictive check and nonparametric bootstrap procedures. Results:Piclozotan PK was well described using a 3-compartment model with first-order elimination. Parameter estimates (intersubject variability) were V1, central volume: 64.0 L (66.5%) and CL, systemic clearance: 18.0 L/h (31.4%). Peripheral volumes (V2, V3) were related to total body weight, whereas CL was related to ideal body weight. Clearance decreased with advancing age, yielding a decrease of 35%-65% in patients aged 70-90. There was no discernable difference in PK between healthy subjects and stroke patients. Conclusions:Piclozotan disposition was well described by the population model, and the intersubject variability around the estimated parameters was moderate in magnitude (<60%). The population PK analysis of piclozotan allows for characterization of piclozotan exposure in individual subjects based on their age and body weight. The availability of a population PK model will facilitate dose optimization and further clinical development of piclozotan.
Using DNA Microarrays To Identify Library-Independent Markers for Bacterial Source Tracking

ABSTRACT Bacterial source tracking is used to apportion fecal pollution among putative sources. Within this context, library-independent markers are genetic or phenotypic traits that can be used to identify the host origin without a need for library-dependent classification functions. The objective of this project was to use mixed-genome Enterococcus microarrays to identify library-independent markers. Separate shotgun libraries were prepared for five host groups (cow, dog, elk/deer, human, and waterfowl), using genomic DNAs (gDNAs) from ca. 50 Enterococcus isolates for each library. Microarrays were constructed (864 probes per library), and 385 comparative genomic hybridizations were used to identify putative markers. PCR assays were used to screen 95 markers against gDNAs from isolates from known sources collected throughout the United States. This validation process narrowed the selection to 15 markers, with 7 having no recognized homologues and the remaining markers being related to genes involved in metabolic pathways and DNA replication. In most cases, each marker was exclusive to one of four Enterococcus species (Enterococcus casseliflavus, E. faecalis, E. hirae, or E. mundtii). Eight markers were highly specific to either cattle, humans, or elk/deer, while the remaining seven markers were positive for various combinations of hosts other than humans. Based on microarray hybridization data, the prevalence of host-specific markers ranged from 2% to 45% of isolates collected from their respective hosts. A 20-fold difference in prevalence could present challenges for the interpretation of library-independent markers.
Structure-based alignment and comparative molecular field analysis of acetylcholinesterase inhibitors.

The method of comparative molecular field analysis (CoMFA) was used to develop quantitative structure-activity relationships for physostigmine, 9-amino-1,2,3,4-tetrahydroacridine (THA), edrophonium (EDR), and other structurally diverse inhibitors of acetylcholinesterase (AChE). The availability of the crystal structures of enzyme/inhibitor complexes (EDR/AChE, THA/AChE, and decamethonium (DCM)/AChE) (Harel, M.; et al. Quaternary ligand binding to aromatic residues in the active-site gorge of acetylcholinesterase. Proc. Natl. Acad. Sci. U.S.A. 1993, 90, 9031-9035) provided information regarding not only the active conformation of the inhibitors but also the relative mutual orientation of the inhibitors in the active site of the enzyme. Crystallographic conformations of EDR and THA were used as templates onto which additional inhibitors were superimposed. The application of cross-validated R2 guided region selection method, recently developed in this laboratory (Cho, S.J.; Tropsha, A. Cross-Validated R2 Guided Region Selection for Comparative Molecular Field Analysis (CoMFA): A Simple Method to Achieve Consistent Results. J. Med. Chem. 1995, 38, 1060-1066), to 60 AChE inhibitors led to a highly predictive CoMFA model with the q2 of 0.734.
A survey of postoperative nausea and vomiting

A prospective interview‐based survey on the incidence of postoperative nausea and vomiting in 1107 in‐patients aged 4–86 years was conducted during a 3‐month period. Nausea, emetic episodes and the need for anti‐emetic medication were recorded for 24 h postoperatively. In the recovery room, the incidence of nausea and vomiting was 18% and 5%, respectively. Over the whole 24‐h period, these figures were 52% and 25%, respectively; severe nausea was experienced by 8%. The highest incidence of emetic sequelae was observed in gynaecological patients; 52% of the 822 patients who received general anaesthesia and 38% of the 285 patients who received regional anaesthesia reported nausea. The most important predictive factors associated with an increased risk for nausea and vomiting were female gender, a previous history of postoperative sickness, a longer duration of surgery, nonsmoking and a history of motion sickness. Based on these five items, a simple score predicting the risk of nausea and vomiting was constructed with a moderately good discriminating power.
Vehicle detection in high resolution satellite images with joint-layer deep convolutional neural networks

Vehicle detection can provide volumes of useful data for city planning and transport management. It has always been a challenging task because of various complicated backgrounds and the relatively small sizes of targets, especially in high resolution satellite images. A novel model called joint-layer deep convolutional neural networks (JLDCNNs), which joins features in the higher layers and the lower layers of deep convolutional neural networks (DCNNs), is proposed in this paper. JLDCNNs aim to cover different scales and detect vehicles from complex satellite images rapidly by overcoming the insufficient feature extraction of traditional DCNNs. The model is evaluated and compared with traditional DCNNs and other methods on our challenging dataset which includes 20 high resolution satellite images (including over 2400 vehicles) collected from Google Earth. JLDCNNs significantly improve the precision rate by 16% and the recall rate by 6% compared with traditional DCNNs, let alone outperform other traditional methods.
Modeling transient electrical disturbances by inductive coupling for the ISO 7637-3 ICC test

In this paper, we model the inductive current clamp (ICC) method described in the ISO 7637-3 standard, where we apply a broadband transient signal as disturbance. To validate the advocated model, a nonlinear device under test (DUT) is simulated, manufactured and measured under the ISO 7637-3 standard test conditions. Furthermore, it is shown that the proposed model can be used to study the DUT's immunity.
From vision to reality: implementing health reforms in Lusaka, Zambia.

This study describes how members of a health team, from the national health system to the local population, implement reform directives and activities in Lusaka, Zambia. In order to determine the influence of the different actors in the health system on the policy outcomes, the study applied the three-dimensional definition of power by Luke and the concept of veto point of Pressman and Wildavsky. This research showed that the different actors expressed agreement on the nature of the National Strategic Health Plan by the Ministry of Health, which became operational in 1995, but the consensus was nevertheless accompanied with opposing attitudes especially on its strong democratization tone. The information provided by the actors also differs in terms of the rationale and implementation mode of policies. Furthermore, in the Lusaka health system, the Minister, district managers, and in-charges were seen as influential on the implementation processes of the reform, sitting in a critical veto point and exercising three types of powers which were expressed through overt, covert, and latent conflicts.
Auction Performance on Wholesale Electricity Markets in the Presence of Transmission Constraints and Transmission Costs

Electricity markets are becoming more integrated around the world. However, the knowledge of the effects of different auction formats on suppliers’ strategies in the presence of transmission constraints and transmission costs is still very limited. In this paper, I analyze the performance of uniform and discriminatory price auctions in the presence of transmission constraints and transmission costs. When the transmission capacity is binding, the discriminatory price auction could outperform the uniform price auction, minimizing the equilibrium price and the transmission costs. Moreover, when the transmission capacity is binding, an increase in transmission costs could be pro-competitive when the auction is discriminatory, but not when the auction is uniform.
Online support communities for older people: Characteristics and dynamics of online social support

More and more people aged 60+ are using the internet. In recent years, older people’s activities online have expanded from information retrieval to include social and communicative activities as well. While email is currently the most prevalent communication activity of older people online, the use of online communities is also growing within this group (Jones & Fox, 2009). Many older people now use online communities on a regular basis, often to find information and support concerning a specific health problem. Scholars and practitioners in the area of Inclusive Design have done a lot of work towards accessible web design for older people by developing guidelines that assert accessibility standards (e.g. Kurniawan & Zaphiris, 2005). The focus of this work has been mainly on the accessibility of information on the internet. However, the increasing amount of social activities on the internet poses new challenges for Inclusive Design researchers. Ensuring access to information on the internet is no longer sufficient: social aspects of activities on the internet should also be considered (Pfeil & Zaphiris, 2009a).
Optical character recognition using artificial neural network

The objective of this work is to convert printed text or handwritten characters recorded offline using either scanning equipment or cameras into a machine-usable text by simulating a neural network so that it would improve the process of collecting and storing data by human workers. Another goal is to provide an alternate, better and faster algorithm with higher accuracy to recognize the characters. In this context, we choose artificial neural network and make it much more tolerant to anomalies in the recorded image or data. Common optical character recognition tasks involve identifying simple edge detection and matching them with predefined patterns. In this research, characters are recognized even when noise such as inclination and skewedness presents, by training the network to look for discrepancies in data and relate them using vocabulary, grammar and common recurrences that may occur after a character. Images are also masked in multiple ways and processed individually to increase the confidence level of prediction.
Cross-sectional and longitudinal risk factors for falls, fear of falling, and falls efficacy in a cohort of middle-aged African Americans.

PURPOSE The purpose of this study is to cross-sectionally and longitudinally identify risk factors for falls, fear of falling, and falls efficacy in late-middle-aged African Americans. DESIGN AND METHODS We performed in-home assessments on a probability sample of 998 African Americans and conducted two annual follow-up interviews. Multiple logistic regression modeled the associations with falls (any fall or injurious fall) during 2 years prior to the baseline interview, and baseline fear of falling and falls efficacy with 2-year prospective risks for falling and fear of falling. RESULTS The most consistent association for all outcomes was depressive symptoms. Age was associated with increased risk of prior and prospective falls. Lower-body functional limitations were associated with prior falls, baseline fear of falling, and low falls efficacy, whereas low ability with one-leg stands prospectively predicted fear of falling. The greatest prospective risk for incident falls was having had a prior fall (odds ratio = 2.51), and the greatest prospective risk for fear of falling was having been afraid of falling at baseline (odds ratio = 8.14). IMPLICATIONS Falls, fear of falling, and low falls efficacy are important issues for late-middle-aged as well as older persons. Interventions should focus on younger adults and attend especially to lower-body function and depressive symptoms as well as building self-efficacy for safe exercise, dealing with falls risks, and managing falls themselves.
Irreversibility of Capital: A Literature Review

Investment is often ‘irreversible’ i.e. once installed; capital has little or no value unless used in production. The term “irreversibility” of capital refers to the situation in which the firm cannot purchase and sell capital at the same price without any transactions costs or adjustment costs. This paper attempts to review the critical points of literature on the topic. The first section describes the neo-classical view of investment ala Jorgenson (1963), concept of irreversibility and fixed costs. The second section describes the concept of user costs in a mathematical framework taken from Abel & Eberly (1998). In the third section, the concept of irreversibility is explained using two models and literature review on the same. The fourth section describes the labor costs. The last two sections pertain to the applications of the concept and directions for future research.
Is Daily Deal a Good Deal for Merchants? An Empirical Analysis of Economic Value in the Daily Deal Market

The daily deals platform has become an important format in the online-to-offline (O2O) business model. However, questions have been raised over whether merchants really benefit from participating in daily deals, with some evidence suggesting that a significant number of merchants are losing money from them. In this paper, we address this question by quantifying the economic value of daily deals using a structural approach. Using data from the Chinese daily deals market, we find that merchants not only profit from daily deals, but also take the biggest share of the economic value created by them. However, the gain mainly comes from future revenue, with merchants typically incurring a loss during the promotion period. We also find that competition among platforms increases the merchant’s share of the economic value. Finally, we show that the competition in the current market is close to the optimal situation from a policy maker’s point of view.
The foldon universe: a survey of structural similarity and self-recognition of independently folding units.

We have identified independently folding units, so called "foldons", from non-homologous proteins representing different folds. We applied simple statistical arguments in order to estimate the size of the foldon universe required to construct all foldable proteins. Various alignment procedures yield about 2600 foldons in the natural protein universe but this estimate is shown to be rather sensitive to the chosen cut-off value for structural similarity. We showed that foldon matching-modelling can reproduce the major part of the main chain of several proteins with a structural similarity measure Q-score of about 0.4 and an r.m.s. error of about 5 A, although the accuracy of structure prediction has been limited so far by the small size of foldon data set. The prediction score may be increased if one uses the set of protein fragments with optimized sequence-structure relationships, in other works, minimally frustrated segments. To quantify the degree of frustration of the structures of foldons from our database, we searched for those foldons which recognize their own sequence and structure upon threading. As a result we found that about half of the foldons from our data set recognize themselves as the best choice upon threading and therefore are individually minimally frustrated. We showed that there is a close connection between the Q-score of self recognition and the relative foldability (Theta) of the folding units. Foldons having high Q-score and Theta values are expected to be formed in the early phase of the folding process and be observed as stable intermediates under appropriate experimental conditions.
Delay-Independent Minimum Dwell Time for Exponential Stability of Uncertain Switched Delay Systems

In this technical note, the problem of delay-independent minimum dwell time for exponential stability of uncertain switched delay systems is considered. Piecewise time-varying Lyapunov functionals/functions which are decreasing at switching times by construction are introduced to investigate exponential stability of switched delay systems with constant or time-varying delays. This type of delicately constructed Lyapunov functionals/functions can efficiently eliminate the “jump” phenomena of adjacent Lyapunov functionals/functions at switching times without imposing any restriction on the sizes of time-delays. By applying this type of Lyapunov functionals/functions, it is shown that if each subsystem is delay-independently exponentially stable, then under some conditions there exists a delay-independent minimum dwell time in the sense that the switched delay system with such minimum dwell time is exponentially stable irrespective of the sizes of the time-delays. Two numerical examples are provided to demonstrate the efficiency of the proposed approach.
Are the recent secular increases in the waist circumference of adults independent of changes in BMI?

BACKGROUND Several studies showed that the waist circumference of US adults has increased over the past 25 y. However, because of the high correlation between waist circumference and body mass index (BMI; in kg/m²) (r ∼ 0.9), it is uncertain if these trends in waist circumference exceed those expected on the basis of BMI changes over this time period. OBJECTIVE We assessed whether the recent trend in waist circumference was independent of changes in BMI, age, and race-ethnicity. DESIGN We analyzed data from the 1999-2000 through 2011-2012 cycles of the NHANES. RESULTS The mean waist circumference increased by ∼2 cm (in men) and ∼4 cm (in women) in adults in the United States over this 12-y period. In men, this increase was very close to what would be expected because of the 0.7 increase in mean BMI over this period. However, in women, most of the secular increase in waist circumference appeared to be independent of changes in BMI (mean: 0.6), age, and race-ethnicity over the 12-y period. We estimated that, independent of changes in these covariates, the mean waist circumference increased by 0.2 cm in men and 2.4 cm in women from 1999-2000 through 2011-2012; only the latter estimate was statistically significant. CONCLUSIONS Our results indicate that, in women but not men, the recent secular trend in waist circumference is greater than what would be expected on the basis of changes in BMI. Possible reasons for this secular increase, along with sex differences, are uncertain.
On Achieving Diversity in Recommender Systems

Throughout our digital lives, we are getting recommendations for about almost everything we do, buy or consume. In that way, the field of recommender systems has been evolving vastly to match the increasing user needs accordingly. News, products, ideas and people are only a few of the things that we can be recommended with daily. However, even with the many years of research, several areas still remain unexplored. The focus of this paper revolves around such an area, namely on how to achieve diversity in single-user and group recommendations. Specifically, we decouple diversity from strictly revolving around items, and consider it as an orthogonal dimension that can be incorporated independently at different times in the recommender's workflow. We consider various definitions of diversity, taking into account either data items or users characteristics, and study how to cope with them, depending on whether we opt at diversity-aware single-user or group recommendations.
An Analytical Approach to the Liquidity Effects of Monetary Policy

This paper characterizes analytically the persistent liquidity effects of a money injection in a model economy with goods market segmentation as well as financial market segmentation. Households in financial sectors receive money transfers from the central bank and have access to the bond market, while others outside financial sectors do not receive money transfers and have no access to the bond market. Also, a shock that causes households to relocate between financial sectors leads to more consumption expenditure for both types of households. This goods market effect then causes a money injection to diffuse through the economy over time, generating persistent liquidity effects even when the money growth shock is transitory. This is empirically important because persistent liquidity effects have been observed in many countries with a relatively low persistence of money growth.
Arbitrage-Free Call Option Surface Construction Using Regression Splines (Preprint)

In this work, we suggest a novel quadratic programming-based algorithm to generate an arbitrage-free call option surface. Our approach relies on a regression spline-based implementation of the framework proposed by Orosi (2011) who presents a multi-parameter extension of the models of Figlewski (2002) and Henderson, Hobson, and Kluge (2007). Moreover, the empirical performance of the proposed method is evaluated using S&P 500 Index call options. Our results indicate that the proposed method provides a more precise fit to observed option prices than other alternative methodologies. NOTE: This is a preprint. The published version has been extensively revised.