Miracle-dz/UniFAR-FTUs huggingface dataset:
The effects of ferulic acid on the pharmacokinetics of warfarin in rats after biliary drainage

According to previous research studies, warfarin can be detected in human bile after oral administration. Ferulic acid (FA) is the main bioactive component of many Chinese herbs for the treatment of cardiovascular disease. To elucidate the effects of FA on the pharmacokinetics of warfarin in rats after biliary drainage is necessary. Twenty rats were randomly divided into four groups: Group 1 (WN): healthy rats after the administration of warfarin sodium, Group 2 (WO): a rat model of biliary drainage after the administration of warfarin sodium, Group 3 (WFN): healthy rats after the administration of warfarin sodium and FA, and Group 4 (WFO): a rat model of biliary drainage after the administration of warfarin sodium and FA. Blood samples were collected at different time points after administration. The concentrations of blood samples were determined by ultraperformance liquid chromatography–tandem mass spectrometry. Comparisons between groups were performed according to the main pharmacokinetic parameters calculated by the DAS 2.1. 1 software. The pharmacokinetic parameters showed a significant difference between the WN and WO groups, the WO group showed a decrease of 51% and 41.6% in area under the curve from 0 to time (AUC0–t) and peak plasma concentration (Cmax), respectively, whereas time to Cmax (Tmax) was delayed 3.27 folds. There were significant differences between the WFO and WFN groups, the WFO group showed a decrease of 63.8% and 70% in AUC0–t and Cmax, respectively; the delay in Tmax between the WN and WFN groups (mean, from 132–432 minutes) was significantly different; the mean retention time from 0 to time (MRT0–t) between the WO and WFO groups (mean, from 718.31–606.13 minutes) also showed a significant difference. Enterohepatic circulation markedly influences the disposition of warfarin in rats, and FA significantly affected the warfarin disposition in rat plasma.
Generation of a conditionally self-eliminating HAC gene delivery vector through incorporation of a tTAVP64 expression cassette

Human artificial chromosome (HAC)-based vectors represent an alternative technology for gene delivery and expression with a potential to overcome the problems caused by virus-based vectors. The recently developed alphoidtetO-HAC has an advantage over other HAC vectors because it can be easily eliminated from cells by inactivation of the HAC kinetochore via binding of chromatin modifiers, tTA or tTS, to its centromeric tetO sequences. This provides a unique control for phenotypes induced by genes loaded into the HAC. The alphoidtetO-HAC elimination is highly efficient when a high level of chromatin modifiers as tetR fusion proteins is achieved following transfection of cells by a retrovirus vector. However, such vectors are potentially mutagenic and might want to be avoided under some circumstances. Here, we describe a novel system that allows verification of phenotypic changes attributed to expression of genes from the HAC without a transfection step. We demonstrated that a single copy of tTAVP64 carrying four tandem repeats of the VP16 domain constitutively expressed from the HAC is capable to generate chromatin changes in the HAC kinetochore that are not compatible with its function. To adopt the alphoidtetO-HAC for routine gene function studies, we constructed a new TAR-BRV- tTAVP64 cloning vector that allows a selective isolation of a gene of interest from genomic DNA in yeast followed by its direct transfer to bacterial cells and subsequent loading into the loxP site of the alphoidtetO-HAC in hamster CHO cells from where the HAC may be MMCT-transferred to the recipient human cells.
Phase Preserving Denoising of Images

In recent years wavelet shrinkage denoising has become the method of choice for the denoising of images. However, despite much research a number of questions remain. Which of the many wavelets that exist should one use? How should the threshold be set? and How are features in the image affected by the thresholding operation? This paper explores these issues and argues for the use of non-orthogonal, complex valued, log-Gabor wavelets, rather than the more usual orthogonal or bi-orthogonal wavelets. Thresholding of wavelet responses in the complex domain allows one to ensure that perceptually important phase information in the image is not corrupted. It is also shown how appropriate threshold values can be determined automatically from the statistics of the wavelet responses to
The impact of strategic disclosure on returns and return volatility : Evidence from the ‘ leverage effect ’

Strategic disclosure, which we define as the reporting of good news and the withholding of bad news, provides an explanation for predictable dynamic patterns in returns including the negative relation between return shocks and conditional return volatility, referred to as the leverage effect. With strategic reporting, positive share price responses in the event of good news result from news arrival. Negative share price responses, in contrast, are more likely due to an inference of bad news, which implies a smaller reduction in residual uncertainty. We document that the leverage effect is stronger in portfolios of individual stocks that are more likely to disclose strategically: The leverage effect is 1) stronger for firms in industries with lower private information, and 2) weaker for firms in industries with a high risk of shareholder litigation. The relationship between strategic disclosure and the leverage effect is greater for high-beta firms, for which patterns in total returns are more likely to reflect the idiosyncratic nature of news that firms choose to disclose strategically. Time-series and cross-sectional patterns in the leverage effect in market indices also are consistent with strategic disclosure as an explanation for it. These analyses are an important component of the study because they indicate that strategic disclosure decisions by individual firms are strong enough not only to create patterns in their own stock returns, but also that they might be powerful enough to explain market-wide patterns despite the covariance effects of aggregation of disclosure behavior over multiple firms. € The University of Chicago † Corresponding author: The Wharton School, University of Pennsylvania, 1300 SH-DH, Philadelphia, PA 191046365. e-mail schrand@wharton.upenn. edu. * The Wharton School of the University of Pennsylvania The authors thank Michael Brandt, Ron Kaniel, Christian Leuz, Russ Lundholm, Pat Hughes and seminar participants at Duke University, Indiana University, Insead, UCLA and the University of Utah Winter Conference for comments. We thank Joseph Gerakos for research assistance on model selection.
Community structure of marine bacterioplankton: patterns, networks, and relationships to function

Major challenges in marine microbial ecology include determining patterns of commu- nity structure and structure-function relationships. Progress has occurred by a combination of mole- cular and classical techniques. An example for this is work on the marine Crenarchaeota, extremely abundant organisms that we now think play important roles both as autotrophic ammonium oxidiz- ers and as heterotrophs. Another involves the recently discovered Proteorhodopsins, pigments that are potentially important in solar energy capture, yet often do not seem to confer a clear growth benefit to organisms that possess them. Proteorhodopsins occur in numerous phylogenetic groups and may have multiple roles, complicating the linking of these proteins to a well-defined function. Community fingerprinting is a powerful tool for examining community structure and for examining spatial and temporal distribution patterns. Using fingerprinting, we found that ocean communities tend to occur in patches with horizontal dimensions of several km, while samples 10s of km or more apart can be quite different. Temporal analyses such as the San Pedro Ocean Time Series (SPOT) show that near-surface communities are somewhat similar from month to month, then change signif- icantly over several months, and finally return to a similar community annually. Near-surface com- munities can also be predicted from environmental parameters like temperature, salinity, nutrients, and chlorophyll. Time series data show co-occurrence of organisms (resembling a succession of com- munities) under particular conditions, or conversely can show which organisms are significantly neg- atively correlated, indicative perhaps of competition, resource partitioning, or allelopathy. These relationships are visualized here as mathematical interaction networks to map out the 'niche space' of microbial taxa and their correlations, displaying complex ecological interactions. Observations indicate that ecological relatedness does not necessarily closely follow phylogenetic relatedness.
Applied Financial Economics , 1998 , 8 , 577 — 587 Modelling real exchange rate beha v iour : a cross-country study

The paper examines the behaviour of bilateral real exchange rates between Germany and fourteen major economies for the period January 1972 to December 1994. Time series techniques are used to consider a number of hypotheses including whether the real exchange rate is mean reverting; whether deviations follow a stable time series process; whether the underlying process can be modelled adequately and whether there is any evidence of risk premia. Evidence is provided that relationships of these sort can indeed be established for a selection of economies and that despite economic policy directed towards exchange rate stability, significant risk premia are present in the bilateral real exchange rates examined.
Influence of pHo on calcium channel block by amlodipine, a charged dihydropyridine compound. Implications for location of the dihydropyridine receptor

We have investigated the modulation of L-type calcium channel currents in isolated ventricular cells by the dihydropyridine derivative amlodipine, a weak base with a pKa of 8.6. Under conditions that favor neutral drug molecules, amlodipine block resembles other, previously described, neutral dihydropyridine derivatives: block is more pronounced at depolarized voltages, repetitive pulsing is not needed to promote block, and recovery is complete at hyperpolarized voltages. When the drug is ionized, depolarized voltages still enhance block, however, the time course is slow and speeded by repetitive pulses that open channels. Recovery from block by ionized drug molecules is very slow and incomplete, but can be rapidly modified by changes in external hydrogen ion concentration. We conclude from these observations that the degree of ionization of the drug molecule can affect access to the dihydropyridine receptor and that external protons can interact with the drug-receptor complex even if channels are blocked and closed. These observations place limitations on the location of this receptor in the ventricular cell membrane.
Genotypic and Phenotypic Characterization of Carriage and Invasive Disease Isolates of Neisseria meningitidis in Finland

ABSTRACT The relationship between carriage and the development of invasive meningococcal disease is not fully understood. We investigated the changes in meningococcal carriage in 892 military recruits in Finland during a nonepidemic period (July 2004 to January 2006) and characterized all of the oropharyngeal meningococcal isolates obtained (n = 215) by using phenotypic (serogrouping and serotyping) and genotypic (porA typing and multilocus sequence typing) methods. For comparison, 84 invasive meningococcal disease strains isolated in Finland between January 2004 and February 2006 were also analyzed. The rate of meningococcal carriage was significantly higher at the end of military service than on arrival (18% versus 2.2%; P < 0.001). Seventy-four percent of serogroupable carriage isolates belonged to serogroup B, and 24% belonged to serogroup Y. Most carriage isolates belonged to the carriage-associated ST-60 clonal complex. However, 21.5% belonged to the hyperinvasive ST-41/44 clonal complex. Isolates belonging to the ST-23 clonal complex were cultured more often from oropharyngeal samples taken during the acute phase of respiratory infection than from samples taken at health examinations at the beginning and end of military service (odds ratio [OR], 6.7; 95% confidence interval [95% CI], 2.7 to 16.4). The ST-32 clonal complex was associated with meningococcal disease (OR, 17.8; 95% CI, 3.8 to 81.2), while the ST-60 clonal complex was associated with carriage (OR, 10.7; 95% CI, 3.3 to 35.2). These findings point to the importance of meningococcal vaccination for military recruits and also to the need for an efficacious vaccine against serogroup B isolates.
Towards a dynamic understanding of burnout

Nurses in the UK currently face significant challenges: Austerity measures and efficiency drives have led to staff shortages (Nursing Times, 2013), and nurses suffering from higher rates of stress-related sickness when compared to other sectors (Foureur et al, 2013). The nature of the nursing role leaves nurses particularly vulnerable to burnout (Farrington, 1995). A pragmatic epistemological framework was adopted to conduct a mixed methods study, with qualitative focus, which set out to retrospectively explore how the nurse becomes vulnerable or resilient to burnout. Initially 100 nurses working in the high intensity fields of cancer care or ITU, in a leading UK, NHS Trust, were invited to take part in a quantitative study exploring burnout levels, using the MBI. 100 took part, 53% showed burnout on at least 1 dimension of burnout, ie. emotional exhaustion. 16 nurses were interviewed qualitatively: 10 showing various degrees/patterns of burnout and 6 showing high levels of resilience to burnout. A modified, analytical approach of classical grounded theory was adopted. Findings suggest burnout is a continuous, multi-faceted process involving a complex interplay of internal/interpersonal/external factors. The process is mediated by how reflective, insightful and adaptable a nurse is to work-based stressors, with marked differences being found between the vulnerable and resilient nurse positions. Of note the inherent preference for taskfocused or emotionally-driven nursing orientations variably influences how burnout develops. The pervasive culture of communication was also identified as significant with the optimum culture being one of understated stoicism, acceptance and collective management of vulnerability. Findings suggest far reaching implications for nursing training policy, selection, nursing practice and intervention development, which should function at the individual/interpersonal and organisational level, taking into account the impact of nursing orientations and the pervasive culture of communication on burnout.
Dissecting the Role of Retinoic Acid Receptor Isoforms in the CD8 Response to Infection

Vitamin A deficiency leads to increased susceptibility to a spectrum of infectious diseases. The studies presented dissect the intrinsic role of each of the retinoic acid receptor (RAR) isoforms in the clonal expansion, differentiation, and survival of pathogen-specific CD8 T cells in vivo. The data show that RARα is required for the expression of gut-homing receptors on CD8+ T cells and survival of CD8+ T cells in vitro. Furthermore, RARα is essential for survival of CD8+ T cells in vivo following Listeria monocytogenes infection. In contrast, RARβ deletion leads to modest deficiency in Ag-specific CD8+ T cell expansion during infection. The defective survival of RARα-deficient CD8+ T cells leads to a deficiency in control of L. monocytogenes expansion in the spleen. To our knowledge, these are the first comparative studies of the role of RAR isoforms in CD8+ T cell immunity.
Defective Ca2+ channel clustering in axon terminals disturbs excitability in motoneurons in spinal muscular atrophy

Proximal spinal muscular atrophy (SMA) is a motoneuron disease for which there is currently no effective treatment. In animal models of SMA, spinal motoneurons exhibit reduced axon elongation and growth cone size. These defects correlate with reduced β-actin messenger RNA and protein levels in distal axons. We show that survival motoneuron gene (Smn)–deficient motoneurons exhibit severe defects in clustering Cav2.2 channels in axonal growth cones. These defects also correlate with a reduced frequency of local Ca2+ transients. In contrast, global spontaneous excitability measured in cell bodies and proximal axons is not reduced. Stimulation of Smn production from the transgenic SMN2 gene by cyclic adenosine monophosphate restores Cav2.2 accumulation and excitability. This may lead to the development of new therapies for SMA that are not focused on enhancing motoneuron survival but instead investigate restoration of growth cone excitability and function.
Are Bt toxins killing aquatic insects ?

Rosi-Marshall, E.J., Tank, J.L. , Royer, T.V. , Whiles, M.R. , Evans-White, M. , Chambers, C. , Griffiths, N.A. , Pokelsek, J., & Stephen, M.L. (2007) Toxins in transgenic crop byproducts may affect headwater stream ecosystems. Proceedings of the National Academy of Sciences of the United States of America, 104, pp 16204-16208 open link: 10.1073/pnas.0707177104 AND http://www.pnas. org/cgi/content/abstract/0707177104v2 AND http://www.botanischergarten. ch/Bt/Rosi-Marschall-Bt-Aquatic-2007.pdf The abstract: “Corn (Zea mays L.) that has been genetically engineered to produce the Cry1Ab protein (Bt corn) is resistant to lepidopteran pests. Bt corn is widely planted in the mid-western United States, often adjacent to headwater streams. We show that corn byproducts, such as pollen and detritus, enter headwater streams and are subject to storage, consumption, and transport to downstream water bodies. Laboratory feeding trials showed that consumption of Bt corn byproducts reduced growth and increased mortality of non-target stream insects. Stream insects are important prey for aquatic and riparian predators, and widespread planting of Bt crops has unexpected ecosystem-scale consequences. ”
The AFPM Model of the Political Business Cycle

Models based on monetary surprises are argued to be unconvincing explanations of the political business cycle, both theoretically and empirically. Instead, we often observe significant pre-electoral increases in fiscal expenditures or transfers, though monetary effects are also present, which we argue may reflect the accommodation of fiscal impulses. We present a model political business cycle model that combines active fiscal policy and passive monetary policy that addresses a number of objections to earlier models. The model stresses the interaction between an independent monetary authority and politicians, with the nature of the cycle depending on the nature of this interaction. In equilibrium the monetary authority accommodates the politicians desired policies in an election year, but is free from political influence in non-election years. Part of this research was done while visiting the Bank of Israel, which I wish to thank for its hospitality. I also with to thank participants at the 2001 CEPR European Summer Symposium in Macroeconomcs (ESSIM), May 30-June 2, 2001, and especially my discussant, John Driffill, for helpful comments.
Quantification of breast stiffness using MR elastography at 3 Tesla with a soft sternal driver: A reproducibility study

Previous studies of breast MR elastography (MRE) evaluated the technique at magnetic field strengths of 1.5 Tesla (T) with the breast in contact with the driver. The aim of this study is to evaluate breast stiffness measurements and their reproducibility using a soft sternal driver at 3T and compare the results with qualitative measures of breast density.
Breadth of anti-merozoite antibody responses is associated with the genetic diversity of asymptomatic Plasmodium falciparum infections and protection against clinical malaria.

BACKGROUND Elucidating the mechanisms of naturally acquired immunity to Plasmodium falciparum infections would be highly valuable for malaria vaccine development. Asymptomatic multiclonal infections have been shown to predict protection from clinical malaria in a transmission-dependent manner, but the mechanisms underlying this are unclear. We assessed the breadth of antibody responses to several vaccine candidate merozoite antigens in relation to the infecting parasite population and clinical immunity. METHODS In a cohort study in Tanzania, 320 children aged 1-16 years who were asymptomatic at baseline were included. We genotyped P. falciparum infections by targeting the msp2 gene using polymerase chain reaction and capillary electrophoresis and measured antibodies to 7 merozoite antigens using a multiplex assay. We assessed the correlation between the number of clones and the breadth of the antibody response, and examined their effects on the risk of malaria during 40 weeks of follow-up using age-adjusted multivariate regression models. RESULTS The antibody breadth was positively correlated with the number of clones (RR [risk ratio], 1.63; 95% confidence interval [CI], 1.32-2.02). Multiclonal infections were associated with a nonsignificant reduction in the risk of malaria in the absence of antibodies (RR, 0.83; 95% CI, .29-2.34). The breadth of the antibody response was significantly associated with a reduced risk of malaria in the absence of infections (RR, 0.25; 95% CI, .09-.66). In combination, these factors were associated with a lower risk of malaria than they were individually (RR, 0.14; 95% CI, .04-.48). CONCLUSIONS These data suggest that malaria vaccines mimicking naturally acquired immunity should ideally induce antibody responses that can be boosted by natural infections.
Steroid-Induced Dendritic Regression Reduces Anatomical Contacts between Neurons during Synaptic Weakening and the Developmental Loss of a Behavior

Steroid hormones alter dendritic architecture in many animals, but the exact relationship between dendritic anatomy, synaptic strength, and behavioral expression is typically unknown. In larvae of the mothManduca sexta, the tip of each abdominal proleg (locomotory appendage) bears an array of mechanosensory hairs, each innervated by a planta hair sensory neuron (PH-SN). In the CNS, PH-SN axons make monosynaptic, excitatory nicotinic cholinergic connections with accessory planta retractor (APR) motoneurons. These synapses mediate a proleg withdrawal reflex behavior that is lost at pupation. The prepupal peak of ecdysteroids (molting hormones) triggers the regression of APR dendrites and a >80% reduction in the amplitude of EPSPs produced in APRs by PH-SNs that innervate posterior planta hairs. The present study tested the hypothesis that a decrease in the number of synaptic contacts from PH-SNs to APRs contributes to this synaptic weakening. Pairs of PH-SNs and APRs were fluorescently labeled in larvae and pupae, and the number of indistinguishably close anatomical contacts (putative synapses) was counted by confocal laser scanning microscopy. During APR dendritic regression, the mean number of contacts from posterior PH-SNs decreased by ∼80%, whereas the size of individual contacts did not change detectably and the axonal arbors of PH-SNs did not regress. These results suggest that the steroid-induced regression of motoneuron dendrites physically disconnects the motoneurons from the synaptic terminals of sensory neurons, producing synaptic weakening and the developmental loss of the proleg withdrawal reflex behavior at pupation.