Miracle-dz/UniFAR-FTUs huggingface dataset:
Metabolism and cytotoxicity of naphthalene and its metabolites in isolated murine Clara cells.

Nonciliated bronchiolar epithelial (Clara) cells of mice are highly susceptible to toxicants that undergo metabolic activation, presumably because this cell type expresses high levels of cytochrome P450 monooxygenases. To establish the capability of these cells to metabolize an agent that causes Clara cell-selective toxicity in vivo, we evaluated the metabolism of naphthalene in isolated cells under two distinct conditions, i.e., in homogenized cell preparations supplemented with glutathione and glutathione S-transferases and in intact cells. In homogenized cell preparations naphthalene was metabolized to dihydrodiol (minor) and a single glutathione adduct (major) derived from the 1R,2S-epoxide. In intact cells the rate of formation of glutathione adduct was much lower and dihydrodiol predominated. Approximately 3-10% of racemic naphthalene oxide added to isolated homogenized cells was converted to glutathione adducts and dihydrodiol in 3-min incubations. At high concentrations of naphthalene oxide (0.25 and 0.5 mM), formation of the adduct derived from the 1R,2s-epoxide was favored. The intracellular glutathione concentration, measured by high performance liquid chromatography as the fluorescence of the monobromobimane-glutathione derivative, was 1.14 +/- 0.13 nmol/10(6) cells. To determine whether Clara cell injury results from cytotoxic metabolites of naphthalene, we assessed viability of intact cells in response to different concentrations of naphthalene and naphthalene metabolites. At high naphthalene concentrations (0.5 and 1.0 mM) cell viability decreased to 63% or less of control, whereas lower concentrations (0.1 or 0.05 mM) did not alter viability significantly. Naphthalene-induced decreases in cell viability were blocked by preincubation of Clara cells with the cytochrome P450 monooxygenase inhibitor piperonyl butoxide. The cytotoxicity of naphthalene metabolites varied. Incubation of cells with 0.5 mM dihydrodiol, 1-naphthol, or 1,2-naphthoquinone decreased cell viability to an extent similar to that produced by 0.5 mM naphthalene. In contrast, 0.5 mM naphthalene oxide and 1,4-naphthoquinone significantly decreased viability more than the parent compound. Preincubation of Clara cells with piperonyl butoxide did not affect the loss in cell viability associated with naphthalene oxide. We conclude that isolated Clara cells 1) are capable of metabolizing naphthalene, a Clara cell-specific cytotoxicant, to two major metabolites, 2) have a detectable intracellular glutathione pool, and 3) are more susceptible to specific naphthalene metabolites than to the parent compound naphthalene.
Chirp characteristics of dual-drive. Mach-Zehnder modulator with a finite DC extinction ratio

In this letter, we present theoretical and experimental studies on the chirp of the dual-drive Mach-Zehnder (MZ) modulator with a finite DC extinction ratio. The chirp of the modulator was measured using the fiber response peak method and compared with the theoretically calculated values. The results show that the residual chirp of the MZ modulator could be substantially reduced by driving the modulator in a push-pull mode with unequal amplitude signals.
A study on the relationship between management team conflict and organizational citizenship behavior in colleges and universities: The mediating effect of organizational justice

The mechanism that team conflict on organizational citizenship behaviors is far from conclusive in the context of Chinese culture. In order to further clarify this mechanism, this study examines the role of organizational justice in the relationship between two types of team conflict and organizational citizenship behavior. Drawing on the samples of 138 management team members in the 14 colleges and universities, the results show that: relationship conflict has significantly negative effect on organizational citizenship behavior and organizational justice respectively; organizational justice has significantly positive effect on organizational citizenship behavior, and organizational justice fully mediates the relationship between relationship conflict and organizational citizenship behaviors. Furthermore, task conflict has significant “inverted U” impact on organizational citizenship behavior and organizational justice respectively; organizational justice mediates the relationship between task conflict and organizational citizenship behavior.
Manifold Kernel Metric Learning for Larger-Scale Image Annotation

An appropriate similarity measure between images is one of the key techniques in search-based image annotation models. In order to capture the nonlinear relationships between visual features and image semantics, many kernel distance metric learning(KML) algorithms have been developed. However, when challenged with large-scale image annotation, their metrics can’t explicitly represent the similarity between image semantics, and their algorithms suffer from high computation cost. Therefore, they always lose their efficiency. In this paper, we propose a manifold kernel metric learning (M KML) algorithm. Our M KML algorithm will simultaneously learn the manifold structure and the image annotation metrics. The main merit of our M KML algorithm is that the distance metrics are builded on image feature’s interior manifold structure, and the dimensionality reduction on manifold structure can handle the high dimensionality challenge faced by KML. Final experiments verify our method’s efficiency and effectiveness by comparing it with state-of-the-art image annotation approaches. key words: image annotation, kernel distance metric learning, manifold structure learning
An Ultralow EOT Ge MOS Device With Tetragonal HfO2 and High Quality HfxGeyO Interfacial Layer

A Ge MOS device with an ultralow equivalent oxide thickness of ~0.5 nm and acceptable leakage current of 0.5 A/cm2 is presented in this paper. The superior characteristics can be attributed to a tetragonal HfO2 with a higher k value (k ~ 31) and comparable bandgap. In addition, a Ge MOS device with tetragonal phase HfO2 (t-HfO2) also shows a lower leakage current and better thermal stability. The mechanisms for t-HfO2 formation may be explained by the little Ge diffusion from Ge substrate and oxygen deficiency, which are obtained by in situ interfacial layer (IL) formation and high-k processes. The IL with k ~ 13 can be formed by in situ H2O plasma treatment. Moreover, a Ge MOS device with the IL grown by H2O plasma shows smaller interface trap density and hysteresis effects due to a high composition of Ge+4.
Neurofibromatosis 2 (NF2) tumor suppressor merlin inhibits phosphatidylinositol 3-kinase through binding to PIKE-L

Neurofibromatosis 2 (NF2) is a tumor suppressor, although the molecular mechanism accounting for this effect remains unknown. Here, we show that merlin exerts its activity by inhibiting phosphatidylinositol 3-kinase (PI3-kinase), through binding to PIKE-L. Wild-type merlin, but not patient-derived mutant (L64P), binds PIKE-L and inhibits PI3-kinase activity. This suppression of PI3-kinase activity results from merlin disrupting the binding of PIKE-L to PI3-kinase. In addition, merlin suppression of PI3-kinase activity as well as schwannoma cell growth is abrogated by a single PIKE-L point mutation (P187L) that cannot bind merlin but can still activate PI3-kinase. Knocking down PIKE-L with RNA interference abolishes merlin's tumor-suppressive activity. Our data support the hypothesis that PIKE-L is an important mediator of merlin growth suppression.
In vivo assessment of pyruvate dehydrogenase flux in the heart using hyperpolarized carbon-13 magnetic resonance

The advent of hyperpolarized 13C magnetic resonance (MR) has provided new potential for the real-time visualization of in vivo metabolic processes. The aim of this work was to use hyperpolarized [1-13C]pyruvate as a metabolic tracer to assess noninvasively the flux through the mitochondrial enzyme complex pyruvate dehydrogenase (PDH) in the rat heart, by measuring the production of bicarbonate (H13CO3−), a byproduct of the PDH-catalyzed conversion of [1-13C]pyruvate to acetyl-CoA. By noninvasively observing a 74% decrease in H13CO3− production in fasted rats compared with fed controls, we have demonstrated that hyperpolarized 13C MR is sensitive to physiological perturbations in PDH flux. Further, we evaluated the ability of the hyperpolarized 13C MR technique to monitor disease progression by examining PDH flux before and 5 days after streptozotocin induction of type 1 diabetes. We detected decreased H13CO3− production with the onset of diabetes that correlated with disease severity. These observations were supported by in vitro investigations of PDH activity as reported in the literature and provided evidence that flux through the PDH enzyme complex can be monitored noninvasively, in vivo, by using hyperpolarized 13C MR.
Impaired selection of relevant positive information in depression

Background: A hallmark characteristic of depression is the inability to regulate the effect of emotional material on cognition. Previous research has demonstrated that depressed individuals are less able than are nondepressed persons to expel irrelevant negative information from working memory (WM), thereby exacerbating the effects of negative content on cognition. The primary goal of this study was to examine whether depressed individuals are also impaired at selecting relevant positive content in the context of representations competing for resources in WM; such an impairment would limit depressed persons' ability to use positive material to ameliorate the cognitive effects of negative information. Methods: We administered a Recency‐probes task with neutral, positive, and negative words to 20 currently depressed and 22 never‐depressed participants. This task assesses the selection of relevant content in WM by inducing interference between current and prior representations of a stimulus in WM. Reaction times to interference and noninterference trials were compared across valence and group to assess how effectively depressed individuals select task‐relevant emotional content to resolve interference. Results: Compared to never‐depressed controls, depressed individuals were impaired in selecting task‐relevant positive stimuli; the performance of the two groups was comparable for selecting task‐relevant neutral and negative stimuli. Conclusions: Findings indicate that a valence‐specific deficit in WM may contribute to the inability of depressed individuals to regulate emotion, and provide empirical support for formulations that implicate positive insensitivity in the maintenance of depression. Depression and Anxiety, 2009. Published 2009 Wiley‐Liss, Inc.
Decline in HIV-1 seroprevalence and low seroconversion rate among injecting drug users at a methadone maintenance program in New York City.

To monitor the trend of HIV-1 seroprevalence, 2,194 newly admitted injecting drug users (IDUs) in a methadone maintenance program in New York City were tested from June 1988 through June 1992. This was a blinded study and unlabeled blood specimens were collected during the required physical examination. There was a significant linear trend (p = .01) toward decline in HIV-1 seropositivity by year of admission as follows: 47.0% in 1988, 43.4% in 1989, 43.2% in 1990, 39.8% in 1991, and 39.1% in 1992. From January 1988 through December 1992, admissions data that included the newly admitted IDUs showed a significant decrease (p < .0002) in self-reported current needle sharing from 11.3% to 5.4%. These two data sources suggest that a continued decline in HIV-1 seroprevalence among new admissions may be related to decreased needle sharing. A volunteer cohort of 235 HIV-1 seronegative IDUs was also enrolled from April 1990 through June 1991 in a study of HIV-1 seroconversion. Follow-up data were available on 177 patients for up to 12 months. For a total observation time of 155 person-years, there were two conversions (1.3 conversions per 100 person-years). A continued decline in HIV-1 seroprevalence among new admissions and a low HIV-1 seroconversion rate among existing patients have contributed to a lower overall HIV-1 prevalence in clinic patients of about 40%. This stands in contrast to 1985-86 estimates of HIV-1 seroprevalence that plateaued at 60%.
Geographic privacy-aware knowledge discovery and delivery

A flood of data pertinent to moving objects is available today, and will be more in the near future, particularly due to the automated collection of privacy-sensitive telecom data from mobile phones and other location-aware devices. Such wealth of data, referenced both in space and time, may enable novel classes of applications of high societal and economic impact, provided that the discovery of consumable and concise knowledge out of these raw data is made possible. Recent research activities have developed theory, techniques and systems for geographic knowledge discovery and delivery, some of them based on privacy-preserving methods for extracting knowledge from large amounts of raw data referenced in space and time. All these efforts aim at devising knowledge discovery and analysis methods for trajectories of moving objects. The fundamental hypothesis is that it is possible, in principle, to aid citizens in their mobile activities by analysing the traces of their past activities by means of data mining techniques. For instance, behavioural patterns derived from mobile trajectories may allow inducing traffic flow information, capable to help people travel efficiently, to help public administrations in traffic-related decision making for sustainable mobility and security management, as well as to help mobile operators in optimising bandwidth and power allocation on the network. On the other hand, it is clear that the use of personal sensitive data arouses concerns about citizen's privacy rights. In this tutorial, we establish a framework for the challenges and the mining solutions for the geographic information collected by Moving Object Database (MOD) engines. We first discuss the challenges of collecting mobility data, and elaborate on the impact of trajectory data analysis in several modern applications. We then discuss methodologies and techniques to collect raw data, reconstruct trajectory information, and efficiently store it in MODs. We continue with an overview of knowledge discovery approaches for movement data. Finally, we propose a research agenda and identify areas where interdisciplinary studies are needed.
Spore Cortex Hydrolysis Precedes Dipicolinic Acid Release during Clostridium difficile Spore Germination

ABSTRACT Bacterial spore germination is a process whereby a dormant spore returns to active, vegetative growth, and this process has largely been studied in the model organism Bacillus subtilis. In B. subtilis, the initiation of germinant receptor-mediated spore germination is divided into two genetically separable stages. Stage I is characterized by the release of dipicolinic acid (DPA) from the spore core. Stage II is characterized by cortex degradation, and stage II is activated by the DPA released during stage I. Thus, DPA release precedes cortex hydrolysis during B. subtilis spore germination. Here, we investigated the timing of DPA release and cortex hydrolysis during Clostridium difficile spore germination and found that cortex hydrolysis precedes DPA release. Inactivation of either the bile acid germinant receptor, cspC, or the cortex hydrolase, sleC, prevented both cortex hydrolysis and DPA release. Because both cortex hydrolysis and DPA release during C. difficile spore germination are dependent on the presence of the germinant receptor and the cortex hydrolase, the release of DPA from the core may rely on the osmotic swelling of the core upon cortex hydrolysis. These results have implications for the hypothesized glycine receptor and suggest that the initiation of germinant receptor-mediated C. difficile spore germination proceeds through a novel germination pathway. IMPORTANCE Clostridium difficile infects antibiotic-treated hosts and spreads between hosts as a dormant spore. In a host, spores germinate to the vegetative form that produces the toxins necessary for disease. C. difficile spore germination is stimulated by certain bile acids and glycine. We recently identified the bile acid germinant receptor as the germination-specific, protease-like CspC. CspC is likely cortex localized, where it can transmit the bile acid signal to the cortex hydrolase, SleC. Due to the differences in location of CspC compared to the Bacillus subtilis germinant receptors, we hypothesized that there are fundamental differences in the germination processes between the model organism and C. difficile. We found that C. difficile spore germination proceeds through a novel pathway.
Review: Global Inequality: A New Approach for the Age of Globalization by Branco Milanovic

How has global inequality changed over the past twenty-five years? This is one of the key questions Branko Milanovic tries to answer in his book Global Inequality, a new approach for the age of globalization. Milanovic stresses that we live in an age of globalization where issues cannot be seen exclusively from national and horizontal perspectives. In his now famous “elephant graph”, he illustrates how the economic gains of globalisation have been distributed unequally. This “growth incidence curve” displays the real gains in household per capita income in relative percentages between 1988 and 2008. Moreover, this curve reveals who can be considered the surprising winners and losers of globalisation. Milanovic argues that the lower middle class of wealthy countries can be considered a loser of globalisation because they have seen little to no growth in real income during the previous quarter of a century. On the other hand, China, India, Thailand, Vietnam and Indonesia have witnessed the rise of a middle class which has experienced significant growth in real income. Together, with global plutocrats – the richest people in the world – they can be seen as the winners of globalisation.
Combinations of Alkaloids Affecting Different Molecular Targets with the Saponin Digitonin Can Synergistically Enhance Trypanocidal Activity against Trypanosoma brucei brucei

ABSTRACT The flagellate Trypanosoma brucei causes sleeping sickness in humans and nagana in animals. Only a few drugs are registered to treat trypanosomiasis, but those drugs show severe side effects. Also, because some pathogen strains have become resistant, new strategies are urgently needed to combat this parasitic disease. An underexplored possibility is the application of combinations of several trypanocidal agents, which may potentiate their trypanocidal activity in a synergistic fashion. In this study, the potential synergism of mutual combinations of bioactive alkaloids and alkaloids with a membrane-active steroidal saponin, digitonin, was explored with regard to their effect on T. b. brucei. Alkaloids were selected that affect different molecular targets: berberine and chelerythrine (intercalation of DNA), piperine (induction of apoptosis), vinblastine (inhibition of microtubule assembly), emetine (intercalation of DNA, inhibition of protein biosynthesis), homoharringtonine (inhibition of protein biosynthesis), and digitonin (membrane permeabilization and uptake facilitation of polar compounds). Most combinations resulted in an enhanced trypanocidal effect. The addition of digitonin significantly stimulated the activity of almost all alkaloids against trypanosomes. The strongest effect was measured in a combination of digitonin with vinblastine. The highest dose reduction indexes (DRI) were measured in the two-drug combination of digitonin or piperine with vinblastine, where the dose of vinblastine could be reduced 9.07-fold or 7.05-fold, respectively. The synergistic effects of mutual combinations of alkaloids and of alkaloids with digitonin present a new avenue to treat trypanosomiasis but one which needs to be corroborated in future animal experiments.
Isolation of Separate Ureaplasma Species From Endotracheal Secretions of Twin Patients

Isolation of Ureaplasma spp. from preterm neonates and the association with development of bronchopulmonary dysplasia has been previously investigated. However, few studies have contrasted the nature of infection in twins. In this article, we report that dizygotic twins (1 girl, 1 boy) born at 24 weeks gestation both yielded culturable Ureaplasma from endotracheal secretions. The samples were part of a serial blind collection cohort of ventilated premature neonates, and analysis of repeat cultures showed stable, separate infections over a period of 17 and 21 days, respectively. Immunoblot and probe-specific quantitative polymerase chain reaction analysis determined that Twin 1 was solely infected with Ureaplasma parvum (specifically, serovar 6 by gene sequencing), whereas Twin 2 was solely infected with Ureaplasma urealyticum (specifically, genotype A- serovars 2, 5, and 8 by gene sequencing). Immunoblot analysis found that the major surface antigen (multiple-banded antigen) altered relative mass for both strains during the course of infection. Quantitative polymerase chain reaction analysis of extracted endotracheal aspirates confirmed no evidence of mixed infection for either twin. Failure of sentinel ventilated preterm infants on the same ward to acquire Ureaplasma infection after the first week of birth suggests no cot-to-cot transfer of Ureaplasma infection occurred. This study demonstrated not only a contrasting clinical outcome for a set of twins infected with 2 separate species of Ureaplasma, but also the first real-time demonstration of multiple-banded antigen alteration and evolution of Ureaplasma over the course of a clinical infection.
H3N2 Influenza Virus Infection Induces Broadly Reactive Hemagglutinin Stalk Antibodies in Humans and Mice

ABSTRACT Broadly neutralizing antibodies directed against the conserved stalk domain of the viral hemagglutinin have attracted increasing attention in recent years. However, only a limited number of stalk antibodies directed against group 2 influenza hemagglutinins have been isolated so far. Also, little is known about the general level of induction of these antibodies by influenza virus vaccination or infection. To characterize the anti-stalk humoral response in the mouse model as well as in humans, chimeric hemagglutinin constructs previously developed in our group were employed in serological assays. Whereas influenza virus infection induced high titers of stalk-reactive antibodies, immunization with inactivated influenza virus vaccines failed to do so in the mouse model. Analysis of serum samples collected from human individuals who were infected by influenza viruses also revealed the induction of stalk-reactive antibodies. Finally, we show that the hemagglutinin stalk-directed antibodies induced in mice and humans have broad reactivity and neutralizing activity in vitro and in vivo. The results of the study point toward the existence of highly conserved epitopes in the stalk domains of group 2 hemagglutinins, which can be targeted for the development of a universal influenza virus vaccine in humans.