Miracle-dz/UniFAR-FTUs huggingface dataset:
Characterization of Human Corneal Epithelial Cell Model As a Surrogate for Corneal Permeability Assessment: Metabolism and Transport

The recently introduced Clonetics human corneal epithelium (cHCE) cell line is considered a promising in vitro permeability model, replacing excised animal cornea to predict corneal permeability of topically administered compounds. The purpose of this study was to further characterize cHCE as a corneal permeability model from both drug metabolism and transport aspects. First, good correlation was found in the permeability values (Papp) obtained from cHCE and rabbit corneas for various ophthalmic drugs and permeability markers. Second, a previously established real-time quantitative polymerase chain reaction method was used to profile mRNA expression of drug-metabolizing enzymes (major cytochromes P450 and UDP glucuronosyltransferase 1A1) and transporters in cHCE in comparison with human cornea. Findings indicated that 1) the mRNA expression of most metabolizing enzymes tested was lower in cHCE than in excised human cornea, 2) the mRNA expression of efflux transporters [multidrug resistant-associated protein (MRP) 1, MRP2, MRP3, and breast cancer resistance protein], peptide transporters (PEPT1 and PEPT2), and organic cation transporters (OCTN1, OCTN2, OCT1, and OCT3) could be detected in cHCE as in human cornea. However, multidrug resistance (MDR) 1 and organic anion transporting polypeptide 2B1 was not detected in cHCE; 3) cHCE was demonstrated to possess both esterase and ketone reductase activities known to be present in human cornea; and 4) transport studies using probe substrates suggested that both active efflux and uptake transport may be limited in cHCE. As the first detailed report to delineate drug metabolism and transport characteristics of cHCE, this work shed light on the usefulness and potential limitations of cHCE in predicting the corneal permeability of ophthalmic drugs, including ester prodrugs, and transporter substrates.
A High-Efficiency Current-Mode Buck Converter With a Power-Loss-Aware Switch-On-Demand Modulation Technique for Multifunction SoCs

Modern multifunction systems on chip often require a high-efficiency buck converter over a wide load current range as the main power source, for which complex multimode operation with mode detection/change is a frequent compromise between efficiency and transient response. This paper proposes a novel power-loss-aware switch-on-demand modulation (PLASOM) technique based on accurate power loss modeling to switch critical components/parameters of power loss on demand: the ON/OFF status and the size of the power transistor, the dead time, and the ON/OFF status of power-hungry subcircuits. The proposed PLASOM-based converter can work as either an adaptive on-time mechanism with constant frequency or a cycle-extended adaptive ON/OFF-time mechanism with variable frequency without mode detection/change, so that the conversion efficiency and transient response can be improved. A proposed buck converter with the PLASOM technique was implemented using the TSMC 90-nm 1/3.3-V CMOS process. Experimental results show that a conversion efficiency higher than 90% was achieved over the 1-500 mA load current range, whereas the voltage variation/recovery time during the 0.1-500 mA load transient were less than 50 mV/25 μs. Performance evaluations indicate that the proposed PLASOM technique is favorable for wide load current range buck converters in terms of conversion efficiency, transient response, and voltage ripples.
THE POPULATION GENETICS OF ADAPTATION ON CORRELATED FITNESS LANDSCAPES: THE BLOCK MODEL

Abstract Several recent theoretical studies of the genetics of adaptation have focused on the mutational landscape model, which considers evolution on rugged fitness landscapes (i.e., ones having many local optima). Adaptation in this model is characterized by several simple results. Here I ask whether these results also hold on correlated fitness landscapes, which are smoother than those considered in the mutational landscape model. In particular, I study the genetics of adaptation in the block model, a tunably rugged model of fitness landscapes. Considering the scenario in which adaptation begins from a high fitness wild-type DNA sequence, I use extreme value theory and computer simulations to study both single adaptive steps and entire adaptive walks. I show that all previous results characterizing single steps in adaptation in the mutational landscape model hold at least approximately on correlated landscapes in the block model; many entire-walk results, however, do not.
Extended-Spectrum β-Lactamase-Producing Klebsiella pneumoniae Strains Causing Nosocomial Outbreaks of Infection in the United Kingdom

ABSTRACT Representative isolates from 10 distinct extended-spectrum β-lactamase-producing strains of Klebsiella pneumoniaethat caused hospital outbreaks in the United Kingdom from 1991 to 1994 were examined for relationships between their enzymes and plasmids. The β-lactamases were identified by a combination of isoelectric focusing and gene sequencing. SHV-2 β-lactamase was produced by isolates from four outbreaks, SHV-5 was involved in three, and SHV-4, TEM-15, and TEM-26 were involved in one outbreak each. All of the extended-spectrum β-lactamases were encoded by self-transmissible plasmids, with sizes ranging from about 70 to 160 kb. No similarities between the restriction digest patterns of the extended-spectrum β-lactamase-encoding plasmids were detected, except to some extent between those that produced TEM-15 and TEM-26. Thus, outbreaks of hospital infection with these organisms in the United Kingdom from 1991 to 1994 involved distinct organisms and resistance plasmids and appeared to be unrelated.
A novel type of interplexiform amacrine cell in the mouse retina

Mammalian retinas comprise an enormous variety of amacrine cells with distinct properties and functions. The present paper describes a new interplexiform amacrine cell type in the mouse retina. A transgenic mouse mutant was used that expressed the gene for the enhanced green fluorescent protein (EGFP) instead of the coding DNA of connexin45 in several retinal cell classes, among which a single amacrine cell population was most prominently labelled. Staining for EGFP and different marker proteins showed that these amacrine cells are interplexiform: they stratify in stratum S4/5 of the inner plexiform layer and send processes to the outer plexiform layer. These cells were termed IPA‐S4/5 cells. They belong to the group of medium‐field amacrine cells and are coupled homologously and heterologously to other amacrine cells by connexin45. Immunostaining revealed that IPA‐S4/5 cells are GABAergic and express GAT‐1, a plasma‐membrane‐bound GABA transporter possibly involved in non‐vesicular GABA release. To characterize the light responses of IPA‐S4/5 cells, patch‐clamp recordings in retinal slices were made. Consistent with their stratification in the ON sublamina of the inner plexiform layer, cells depolarized in response to light ON stimuli and transiently hyperpolarized in response to light OFF. Responses of cells to green (578 nm) and blue (400 nm) light suggest that they receive input from cone bipolar cells contacting both M‐ and S‐cones, possibly with reduced S‐cone input. A new type of interplexiform ON amacrine cell is described, which is strongly coupled and uses GABA but not dopamine as its neurotransmitter.
Gamma-ray burst theory after Swift

Afterglow observations in the pre-Swift era confirmed to a large extend the relativistic blast wave model for gamma-ray bursts (GRBs). Together with the observations of properties of host galaxies and the association with (type Ic) SNe, this has led to the generally accepted collapsar origin of long GRBs. However, most of the afterglow data was collected hours after the burst. The X-ray telescope and the UV/optical telescope onboard Swift are able to slew to the direction of a burst in real time and record the early broadband afterglow light curves. These observations, and in particular the X-ray observations, resulted in many surprises. While we have anticipated a smooth transition from the prompt emission to the afterglow, many observed that early light curves are drastically different. We review here how these observations are changing our understanding of GRBs.
Dynamic range expansion of a Shack-Hartmann sensor by use of a modified unwrapping algorithm.

An algorithm for expanding the dynamic range of Shack--Hartmann sensors is proposed. The distribution of the spot dislocations is treated with a modified unwrapping algorithm that is widely used in interferometry. The algorithm unwraps the spot dislocations and assigns the spots to their original subapertures, leading to a huge expansion of the dynamic range. For the proposed algorithm there remains a limitation on the maximum wave-front curvature instead of on the maximum wave-front slope. Examples are given that show spot fields that were wrapped four times; the measured wave front had a peak-to-valley value of 116 lambda .
The Spanish Block of the Escb-Multi-Country Model

This paper presents the Spanish country block (ES-MCM) of the ESCB Multi-Country Model for the euro area, which has been built in a close co-operation with the ECB and the Banco de Espaa. The theoretical structure of the ES-MCM block is in line with most current mainstream macro models, i.e. the supply factors determine the long-run equilibrium, while in the short run output is demand-determined, resulting from a sluggish adjustment of prices and quantities. The paper is structured as follows. First, a simplified theoretical counterpart of the ES-MCM block is presented and its steady-state comparative statistics and stock-flow equilibrium properties are studied. The theoretical analysis is followed by the review of the estimated equations of the ES-MCM block. Finally the simulation properties of the ES-MCM block are presented in the light of five alternative shock simulations. JEL Classification: E10, E13, E17
FR104, an Antagonist Anti‐CD28 Monovalent Fab' Antibody, Prevents Alloimmunization and Allows Calcineurin Inhibitor Minimization in Nonhuman Primate Renal Allograft

Selective targeting of CD28 might represent an effective immunomodulation strategy by preventing T cell costimulation, while favoring coinhibition since inhibitory signals transmitted through CTLA‐4; PD‐L1 and B7 would not be affected. We previously showed in vitro and in vivo that anti‐CD28 antagonists suppress effector T cells while enhancing regulatory T cell (Treg) suppression and immune tolerance. Here, we evaluate FR104, a novel antagonist pegylated anti‐CD28 Fab' antibody fragment, in nonhuman primate renal allotransplantation. FR104, in association with low doses of tacrolimus or with rapamycin in a steroid‐free therapy, prevents acute rejection and alloantibody development and prolongs allograft survival. However, when FR104 was associated with mycophenolate mofetil and steroids, half of the recipients rejected their grafts prematurely. Finally, we observed an accumulation of Helios‐negative Tregs in the blood and within the graft after FR104 therapy, confirmed by Treg‐specific demethylated region DNA analysis. In conclusion, FR104 reinforces immunosuppression in calcineurin inhibitor (CNI)‐low or CNI‐free protocols, without the need of steroids. Accumulation of intragraft Tregs suggested the promotion of immunoregulatory mechanisms. Selective CD28 antagonists might become an alternative CNI‐sparing strategy to B7 antagonists for kidney transplant recipients.
Statistical Power for Nonequivalent Pretest-Posttest Designs

Nonequivalent controlled pretest-posttest designs are central to evaluation science, yet no practical and unified approach for estimating power in the two most widely used analytic approaches to these designs exists. This article fills the gap by presenting and comparing useful, unified power formulas for ANCOVA and change-score analyses, indicating the implications of each on sample-size requirements. The authors close with practical recommendations for evaluators. Mathematical details and a simple spreadsheet approach are included in appendices.
K-sets+: A linear-time clustering algorithm for data points with a sparse similarity measure

In this paper, we first propose a new iterative algorithm, called the K-sets+ algorithm for clustering data points in a semi-metric space, where the distance measure does not necessarily satisfy the triangular inequality. We show that the K-sets+ algorithm converges in a finite number of iterations and it retains the same performance guarantee as the K-sets algorithm for clustering data points in a metric space. We then extend the applicability of the K-sets+ algorithm from data points in a semi-metric space to data points that only have a symmetric similarity measure. Such an extension leads to great reduction of computational complexity. In particular, for an n × n similarity matrix with m nonzero elements in the matrix, the computational complexity of the K-sets+ algorithm is O((Kn + m)I), where I is the number of iterations. The memory complexity to achieve that computational complexity is O(Kn + m). As such, both the computational complexity and the memory complexity are linear in n when the n × n similarity matrix is sparse, i.e., m = O (n). We also conduct various experiments to show the effectiveness of the K-sets+ algorithm by using a synthetic dataset from the stochastic block model and a real network from the WonderNetwork website.
Generation of RNA pseudoknots with controlled ambiguous grammar

A controlled ambiguous grammar has been suggested to generate more than one parse tree for the prediction of various RNA secondary structures of a given RNA sequence. More than one parse tree implies various formations of RNA pseudoknots for the same RNA sequence reflecting pH, temperature, etc. The use of controlled ambiguous grammar is a novel approach in that the ambiguity of a programming language grammar has been utilized, that should be avoided when making a practical programming language. In this study, a controlled ambiguity of context-free grammar corresponding to the value of pH parameter has been suggested to generate various configuration of RNA pseudokots.
Modeling Asymmetric Comovements of Asset Returns

Existing time-varying covariance models usually impose strong restrictions on how past shocks affect the forecasted covariance matrix. In this article we compare the restrictions imposed by the four most popular multivariate GARCH models, and introduce a set of robust conditional moment tests to detect misspecification. We demonstrate that the choice of a multivariate volatility model can lead to substantially different conclusions in any application that involves forecasting dynamic covariance matrices (like estimating the optimal hedge ratio or deriving the risk minimizing portfolio). We therefore introduce a general model which nests these four models and their natural 'asymmetric' extensions. The new model is applied to study the dynamic relation between large and small firm returns. Article published by Oxford University Press on behalf of the Society for Financial Studies in its journal, The Review of Financial Studies.
Extending Marketing Activities and Strategies from Domestic to Foreign Markets

Abstract Extending marketing activities and strategies from a firm's domestic market to its foreign markets is often viewed as being synonymous with standardization of activities/strategies. However, they can be distinctly different. Standardization generally is an end result and a process, while extension (also a process and end result) can be viewed as being concerned with the source of the standardization. This paper develops a model of the extension phenomenon which links specified antecedents to extension and extension with firm specific advantages, which then lead to performance. Propositions derived from this model are tested by examining the behavior and perceptions of a sample of managers of Hong Kong companies.
Smooth structural breaks and the stationarity of the yen real exchange rates

This article examines and solves an interesting paradox in the literature that the tests for purchasing power parity (PPP) based on the yen real exchange rates (RERs) refute the PPP hypothesis more often than those with other major currency-based RERs, and the evidence is sensitive to the sample period used. Using a new empirical methodology accounting for both nonlinearity and multiple smooth temporary breaks in the data, we show that the puzzling finding is due to the failure to take into account the long but temporary large rise and fall in the yen RERs. The results illustrate that the yen RERs in the post-Bretton Woods period are likely mean reverting with linear or nonlinear adjustment toward large, long swing type of infrequent smooth temporary changes around constant equilibrium values, supporting the validity of PPP and resolving the paradox.
Stimulation of clover root hair infection by lectin-binding oligosaccharides from the capsular and extracellular polysaccharides of Rhizobium trifolii

A polysaccharide depolymerase isolated from the phage lysate of Rhizobium trifolii 4S was used to fragment capsular polysaccharides (CPS) and extracellular polysaccharides (EPS) of R. trifolii 0403 into oligosaccharides. These products were analyzed for clover lectin (trifoliin A)-binding ability, effect on infection of white clover root hairs, and changes in glycosyl and noncarbohydrate composition with culture age. The oligosaccharides from CPS of cultures grown on agar plates for 3, 5, and 7 days exhibited lectin-binding ability at levels similar to those of the corresponding intact CPS. The intact EPS did not bind to clover lectin, although the oligosaccharide fragments from EPS did. In contrast, oligosaccharides from deacetylated CPS had less than half the lectin-binding ability of the native polysaccharide substrate. The CPS from 5-day-old cultures, its corresponding oligosaccharide fragments, and the oligosaccharide fragments of EPS from 5-day-old cultures, all at a concentration of 2.5 micrograms per seedling, stimulated infection thread formation in root hairs of clover seedlings inoculated with R. trifolii 0403. Thus, this bacteriophage-induced polysaccharide depolymerase converted the acidic CPS and EPS of R. trifolii 0403 into biologically active oligosaccharides capable of binding trifoliin A and stimulating root hair infection. The amount of the noncarbohydrate substitutions (pyruvate, acetate, and ether-linked 3-hydroxybutyrate) in the CPS oligosaccharides changed with culture age as shown by 1H-nuclear magnetic resonance spectroscopy. The binding of trifoliin A, therefore, appears to be sensitive to changes in the degree of substitution of noncarbohydrate substitutions in the CPS of R. trifolii 0403.
Efficient Algorithms for Throughput Maximization in Software-Defined Networks With Consolidated Middleboxes

Today’s computer networks rely on a wide spectrum of specialized middleboxes to improve network security and performance. A promising emerging technique to implementing traditional middleboxes is the consolidated middlebox technique, which implements the middleboxes as software in virtual machines in software-defined networks (SDNs), offering economical, and simplified management for middleboxes. This however poses a great challenge, that is, how to find a cost-optimal routing path for each user request such that the data traffic of the request will pass through the middleboxes in their orders in the service chain of the request, with the objective to maximize the network throughput, subject to various resource capacity constraints in SDNs. In this paper, we study the network throughput maximization problem in an SDN under two different scenarios: one is the snapshot scenario where a set of requests at one time slot is given, we aim to admit as many requests in the set as possible to maximize the network throughput; another is the online scenario in which requests arrive one by one without the knowledge of future arrivals. Given a finite time horizon consisting of ${T}$ equal time slots, the system must respond to the arrived requests in the beginning of each time slot, by either admitting or rejecting the requests, depending on the resource availabilities in the network. For the snapshot scenario, we first formulate an integer linear program (ILP) solution, we then devise two heuristics that strive for fine tradeoffs between the quality of a solution and the running time of obtaining the solution. For the online scenario, we show how to extend the proposed algorithms for the snapshot scenario to solve the online scenario. We finally evaluate the performance of the proposed algorithms through experimental simulations, based on both real and synthetic network topologies. Experimental results demonstrate that the proposed algorithms admit more requests than the baseline algorithm and the quality of the solutions delivered by heuristics is comparable to the exact solution by the ILP in most cases.
Passive Coherent Location as Cognitive Radar

Cognitive Radar describes a generic radar system that is capable of adapting its transmission waveforms and cooperation with other sensors in order to achieve superior detection, recognition, and tracking of targets. For example, the sensors of a cognitive radar system might use the illumination signals to carry broadcast data, allowing the sharing of target information. Herein, we postulate that it would be possible to implement a cognitive version of Passive Coherent Location (PCL) which has much in common with the broad cognitive radar concept, but adapts only to the waveforms it senses in the environment, and exploits those that are most useful to it for target detection. In addition, it would model the terrain to improve coverage and provide countermeasures against direct signal saturation. By its name, PCL does not transmit, but relies on emissions from other radiating systems, such as broadcast services, other radars, cellular radio, WiFi, and so on. It is clear that such a system, consisting of multiple, cooperating receivers, can achieve excellent performance in the presence of deliberate jamming, difficult terrain, and attempts at target stealth. In the civilian radar domain, the technology offers opportunities for bandwidth conservation.
LABOUR SUPPLY, INCOME TAXES AND HOURS RESTRICTIONS IN THE NETHERLANDS

In this paper, two models of individual labor supply are discussed. The first one is the by now classical Hausman-type model with convex piecewise linear budget constraints, in which both random preferences and optimization errors are incorporated by means of normally distributed random variables. Estimated coefficients are plausible but the model has the shortcoming that unemployment for males is not captured and that the simulated hours distribution misses the spikes in the sample distribution of working hours. Therefore, an alternative model is introduced which explicitly takes into account demand side restrictions on working hours. The difference with the standard model is the replacement of the optimization error by the assumption that each individual can choose from a finite set of wage hours packages and either picks the job offer yielding highest utility or decides not to work. It turns out that this model captures the sample distribution of working hours very well, for males as well as females. Wage and income elasticities according to the two models are similar and in line with other recent findings in The Netherlands. Dead weight loss calculations for the second model which explicitly take the hours restrictions into account, imply that the dead weight loss is much smaller than as calculated with the standard model. (This abstract was borrowed from another version of this item.)