Miracle-dz/UniFAR-FTUs huggingface dataset:
DETECTION OF GLUTATHIONE CONJUGATES DERIVED FROM 4-IPOMEANOL METABOLISM IN BILE OF RATS BY LIQUID CHROMATOGRAPHY-TANDEM MASS SPECTROMETRY

Earlier studies postulated that bioactivation of 4-ipomeanol by cytochrome P450 enzymes may occur through oxidation of its furan ring, following a mechanism similar to the bioactivation of other furan-containing compounds. This would lead to the formation of furan epoxides and α,β-unsaturated di-aldehyde-reactive metabolites that can conjugate with glutathione. These metabolites are thought to be responsible for the cytotoxic and anticancer properties of 4-ipomeanol. We hypothesized that if 4-ipomeanol is metabolized following this pathway, its glutathione conjugates would be isobaric (molecular ion mass = 492 Da) and would be excreted in bile. To investigate this hypothesis, we analyzed by liquid chromatography-tandem mass spectrometry the bile of rats administered d0/d6 4-ipomeanol (1:1 ratio) intravenously. Hexadeuterated 4-ipomeanol had all deuterium atoms incorporated on its aliphatic chain. Multiple reaction monitoring scans of bile for the mass transition: MH+/(MH - 129)+, which is characteristic of glutathione conjugates, detected four glutathione conjugates. The observation of the isotope cluster (M + 1)+ (d0)/(MH + 6)+ (d6) in a 1:1 molar ratio confirmed that these conjugates were derived from 4-ipomeanol. Retention of the six deuterium atoms in the glutathione conjugates detected, (MH + 6)+, indicates that the bioactivation of 4-ipomeanol took place on the furan ring moiety. Rat hepatic microsomal incubations provided additional evidence. From this study, the mass of the reactive metabolites of 4-ipomeanol can be inferred. The inferred mass (186 Da) matches the mass postulated. A pathway of 4-ipomeanol bioactivation is proposed here. This work represents one step forward to understanding the mechanism of bioactivation of 4-ipomeanol.
Monoclonal antibodies versus reverse transcription‐PCR for detection of respiratory viruses in a patient population with respiratory tract infections admitted to hospital

In the winter season 2001–2002, 239 nasopharyngeal aspirate and 15 bronchoalveolar lavage samples from 208 patients (135 pediatric and 73 adults, including 19 lung transplant recipients) admitted to hospital because of an acute respiratory tract infection were examined for rapid diagnosis of respiratory viruses by two diagnostic approaches: immunological, using specific monoclonal antibodies (MAb); and molecular, using specific reverse transcription (RT)‐PCR assays. Both methods detected influenza viruses A (H1N1 and H3N2) and B, human parainfluenza virus types 1 to 3, human respiratory syncytial virus (hRSV) types A and B, and human adenoviruses. In addition, human coronavirus (hCoV) groups I (229E‐like) and II (OC43‐like), as well as the new human metapneumovirus (hMPV), types A and B, were searched for by RT‐PCR alone. When results obtained by both methods were added, the overall percentage of patients positive for at least one respiratory virus peaked at 44.2%, involving 92/208 patients (81 pediatric, and 11 adults), while 116 patients (55.8%) were negative for any respiratory virus tested. The most common circulating virus was hRSV, infecting 54 (25.9%) patients (24 type A, and 30 type B strains), followed by hMPV, infecting 12 (5.8%) patients (7 type A and 5 type B strains). Coinfections by two respiratory viruses interested 11 (5.3%) patients, and 9 (81.8%) of these were infected by hRSV in association with another respiratory virus. In the great majority of infected children, hRSV and hMPV were associated with lower respiratory tract infections. In lung transplant recipients, viruses present in bronchoalveolar lavage appeared to be associated frequently with lower respiratory tract infections. In conclusion: the combination of immunological and molecular assays is the most sensitive approach to the diagnosis of respiratory viral infections; and infections caused by the less investigated hCoVs and hMPVs represent a fair proportion of respiratory infections. J. Med. Virol. 75:336–347, 2005. © 2004 Wiley‐Liss, Inc.
Approaching questions in forensic authorship analysis

This chapter demonstrates diversity in the activity of authorship and the corresponding diversity of forensic authorship analysis questions and techniques. Authorship is discussed in terms of Love’s (2002) multifunctional description of precursory, executive, declarative and revisionary authorship activities and the implications of this distinction for forensic problem solving. Four different authorship questions are considered. These are ‘How was the text produced? ’, ‘How many people wrote the text? ’, ‘What kind of person wrote the text? ’ and ‘What is the relationship of a queried text with comparison texts? ’ Different approaches to forensic authorship analysis are discussed in terms of their appropriateness to answering different authorship questions. The conclusion drawn is that no one technique will ever be appropriate to all problems.
Early Deafness Increases the Face Inversion Effect But Does Not Modulate the Composite Face Effect

Early deprivation in audition can have striking effects on the development of visual processing. Here we investigated whether early deafness induces changes in holistic/configural face processing. To this end, we compared the results of a group of early deaf participants to those of a group of hearing participants in an inversion-matching task (Experiment 1) and a composite face task (Experiment 2). We hypothesized that deaf individuals would show an enhanced inversion effect and/or an increased composite face effect compared to hearing controls in case of enhanced holistic/configural face processing. Conversely, these effects would be reduced if they rely more on facial features than hearing controls. As a result, we found that deaf individuals showed an increased inversion effect for faces, but not for non-face objects. They were also significantly slower than hearing controls to match inverted faces. However, the two populations did not differ regarding the overall size of their composite face effect. Altogether these results suggest that early deafness does not enhance or reduce the amount of holistic/configural processing devoted to faces but may increase the dependency on this mode of processing.
Effects of manganese on the microstructures of Chenopodium ambrosioides L., A manganese tolerant plant

ABSTRACT Chenopodium ambrosioides L. can tolerate high concentrations of manganese and has potential for its use in the revegetation of manganese mine tailings. Following a hydroponic investigation, transmission electron microscopy (TEM)-energy disperse spectroscopy (EDS) was used to study microstructure changes and the possible accumulation of Mn in leaf cells of C. ambrosioides in different Mn treatments (200, 1000, 10000 μmol·L−1). At 200 μmol·L−1, the ultrastructure of C. ambrosioides was clearly visible without any obvious damage. At 1000 μmol·L−1, the root, stem and leaf cells remained intact, and the organelles were clearly visible without any obvious damage. However, when the Mn concentration exceeded 1000 μmol·L−1 the number of mitochondria in root cells decreased and the chloroplasts in stem cells showed a decrease in grana lamellae and osmiophilic granules. Compared to controls, treatment with 1000 μmol·L−1 or 10000 μmol·L−1 Mn over 30 days, gave rise to black agglomerations in the cells. At 10000 μmol·L−1, Mn was observed to form acicular structures in leaf cells and intercellular spaces, which may be a form of tolerance and accumulation of Mn in C. ambrosioides. This study has furthered the understanding of Mn tolerance mechanisms in plants, and is potential for the revegetation of Mn-polluted soils.
Quarkonia and their transitions

Valuable data on quarkonia (the bound states of a heavy quark $Q=c,b$ and the corresponding antiquark) have recently been provided by a variety of sources, mainly ${e}^{+}{e}^{\ensuremath{-}}$ collisions, but also hadronic interactions. This permits a thorough updating of the experimental and theoretical status of electromagnetic and strong transitions in quarkonia. The $Q\overline{Q}$ transitions to other $Q\overline{Q}$ states are discussed, with some reference to processes involving $Q\overline{Q}$ annihilation.
WaveNet: A Generative Model for Raw Audio

This paper introduces WaveNet, a deep neural network for generating raw audio waveforms. The model is fully probabilistic and autoregressive, with the predictive distribution for each audio sample conditioned on all previous ones; nonetheless we show that it can be efficiently trained on data with tens of thousands of samples per second of audio. When applied to text-to-speech, it yields state-of-the-art performance, with human listeners rating it as significantly more natural sounding than the best parametric and concatenative systems for both English and Mandarin. A single WaveNet can capture the characteristics of many different speakers with equal fidelity, and can switch between them by conditioning on the speaker identity. When trained to model music, we find that it generates novel and often highly realistic musical fragments. We also show that it can be employed as a discriminative model, returning promising results for phoneme recognition.
Effects of Positive Allosteric Modulators on Single-Cell Oscillatory Ca2+ Signaling Initiated by the Type 5 Metabotropic Glutamate Receptor

Agonist stimulation of the type 5 metabotropic glutamate (mGlu5) receptor initiates robust oscillatory changes in cytosolic Ca2+ concentration ([Ca2+]i) in single cells by rapid, repeated cycles of phosphorylation/dephosphorylation of the mGlu5 receptor, involving protein kinase C and as-yet-unspecified protein phosphatase activities. An emergent property of this type of Ca2+ oscillation-generating mechanism (termed “dynamic uncoupling”) is that once a threshold concentration has been reached to initiate the Ca2+ oscillation, its frequency is largely insensitive to further increases in orthosteric agonist concentration. Here, we report the effects of positive allosteric modulators (PAMs) on the patterns of single-cell Ca2+ signaling in recombinant and native mGlu5 receptor-expressing systems. In a Chinese hamster ovary cell-line (CHO-lac-mGlu5a), none of the mGlu5 receptor PAMs studied [3,3′-difluorobenzaldazine (DFB), N-{4-chloro-2-[(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl) methyl]phenyl}-2-hydroxy-benzamide (CPPHA), 3-cyano-N-(1, 3-diphenyl-1H-prazol-5-yl)benzamide (CDPPB), S-(4-fluoro-phenyl)-{3-[3-(4-fluoro-phenyl)-[1,2,4]oxadiazol-5-yl]-piperidinl-1-yl}-methanone (ADX47273)], stimulated a Ca2+ response when applied alone, but each PAM concentration-dependently increased the frequency, without affecting the amplitude, of Ca2+ oscillations induced by glutamate or quisqualate. Therefore, PAMs can cause graded increases (and negative allosteric modulator-graded decreases) in the Ca2+ oscillation frequency stimulated by orthosteric agonist. Initial data in rat cerebrocortical astrocytes demonstrated that similar effects of PAMs could be observed in a native cell background, although at high orthosteric agonist concentrations, PAM addition could much more often be seen to drive rapid Ca2+ oscillations into peak-plateau responses. These data demonstrate that allosteric modulators can “tune” the Ca2+ oscillation frequency initiated by mGlu5 receptor activation, and this might allow pharmacological modification of the downstream processes (e.g., transcriptional regulation) that is unachievable through orthosteric ligand interactions.
Could the Fermi Large Area Telescope detect γ-rays from dark matter annihilation in the dwarf galaxies of the Local Group?

Context. The detection of γ-rays from dark matter (DM) annihilation is among the scientific goals of the Fermi Large Area Telescope (formerly known as GLAST) and Cherenkov telescopes. Aims. In this paper we investigate the chances of such a discovery, selecting some nearby dwarf spheroidal galaxies (dSph) as a target, and adopting the DM density profiles derived from both astronomical observations and N-body simulations. We also make use of recent studies about the presence of black holes and of a population of sub-subhalos inside the Local Group (LG) dwarfs to carry out boost factor studies. Methods. We study the detectability with the Fermi-LAT of the γ-ray flux from DM annihilation in four of the nearest and highly DM-dominated dSph galaxies of the LG, namely Draco, Ursa Minor, Carina, and Sextans, for which state-of-art DM density profiles were available. We assume the DM is made of weakly interacting massive particles such as the lightest supersymmetric particle and compute the expected γ-ray flux for estimations of the unknown underlying particle physics parameters. We then compute the boost factors due to the presence of DM clumps and of a central supermassive black hole. Finally, we compare our predictions with the Fermi-LAT sensitivity maps. Results. We find that the dSph galaxies shine above the Galactic smooth halo: e.g., the Galactic halo is brighter than the Draco dSph only for angles smaller than 2.3 degrees above the Galactic Center. We also find that the presence of a cusp or a constant density core in the DM mass density profile does not produce any relevant effects in the γ-ray flux due to the fortunate combination of the geometrical acceptance of the Fermi-LAT detector and the distance of the galaxies. Moreover, no significant enhancement is given by the presence of a central black hole or a population of sub-subhalos. Conclusions. We conclude that, even for the most optimistic scenario of particle physics, the γ-ray flux from DM annihilation in the dSph galaxies of the LG would be too low to be detected with the Fermi-LAT.
Randomized Controlled Field Trials of Predictive Policing

The concentration of police resources in stable crime hotspots has proven effective in reducing crime, but the extent to which police can disrupt dynamically changing crime hotspots is unknown. Police must be able to anticipate the future location of dynamic hotspots to disrupt them. Here we report results of two randomized controlled trials of near real-time epidemic-type aftershock sequence (ETAS) crime forecasting, one trial within three divisions of the Los Angeles Police Department and the other trial within two divisions of the Kent Police Department (United Kingdom). We investigate the extent to which (i) ETAS models of short-term crime risk outperform existing best practice of hotspot maps produced by dedicated crime analysts, (ii) police officers in the field can dynamically patrol predicted hotspots given limited resources, and (iii) crime can be reduced by predictive policing algorithms under realistic law enforcement resource constraints. While previous hotspot policing experiments fix treatment and control hotspots throughout the experimental period, we use a novel experimental design to allow treatment and control hotspots to change dynamically over the course of the experiment. Our results show that ETAS models predict 1.4–2.2 times as much crime compared to a dedicated crime analyst using existing criminal intelligence and hotspot mapping practice. Police patrols using ETAS forecasts led to an average 7.4% reduction in crime volume as a function of patrol time, whereas patrols based upon analyst predictions showed no significant effect. Dynamic police patrol in response to ETAS crime forecasts can disrupt opportunities for crime and lead to real crime reductions.
Predictors of mental health service utilization by people using resources for homeless people in Canada.

OBJECTIVE This study used Pescosolido's network episode model to examine mental health service utilization among impoverished people accessing resources for the homeless in Canada's universal health care setting. METHODS The sample consisted of 439 people who met DSM-IV criteria for affective or psychotic disorders who were assessed as part of a larger study of resources for homeless or impoverished people in Montreal and Quebec City. Interviews were organized into the framework of four network episode model concepts: sociodemographic characteristics, illness characteristics, illness history, and social network. These blocks of variables were then analyzed in terms of their accuracy in predicting mental health service utilization. RESULTS Eighty-four percent of the sample were male, the mean+/-SD age was 41+/-12 years, and 36% were homeless at the time of the interview, but nearly half (48%) of the population had been homeless previously. The research shows that each network episode model concept except illness history significantly predicted utilization of mental health services. Female gender, youth, never being homeless (sociodemographic characteristics), presence of antisocial personality disorders within the preceding year, past or current alcohol-related disorders (illness characteristics), hospitalization before the preceding year (illness history), and a larger social support network were related to utilization of mental health services. CONCLUSIONS In the absence of economic barriers to health care, there are other significant barriers to the use of mental health services for people who live in poverty. A better understanding of these factors will help in meeting the service needs of impoverished mentally ill people.
Mice with Spontaneous Pancreatic Cancer Naturally Develop MUC-1-Specific CTLs That Eradicate Tumors When Adoptively Transferred1

Pancreatic cancer is a highly aggressive, treatment refractory cancer and is the fourth leading cause of death in the United States. In humans, 90% of pancreatic adenocarcinomas overexpress altered forms of a tumor-specific Ag, mucin 1 (MUC1; an epithelial mucin glycoprotein), which is a potential target for immunotherapy. We have established a clinically relevant animal model for pancreatic cancer by developing a double transgenic mouse model (called MET) that expresses human MUC1 as self molecule and develops spontaneous tumors of the pancreas. These mice exhibit acinar cell dysplasia at birth, which progresses to microadenomas and acinar cell carcinomas. The tumors express large amounts of underglycosylated MUC1 similar to humans. Tumor-bearing MET mice develop low affinity MUC1-specific CTLs that have no effect on the spontaneously occurring pancreatic tumors in vivo. However, adoptive transfer of these CTLs was able to completely eradicate MUC1-expressing injectable tumors in MUC1 transgenic mice, and these mice developed long-term immunity. These CTLs were MHC class I restricted and recognized peptide epitopes in the immunodominant tandem repeat region of MUC1. The MET mice appropriately mimic the human condition and are an excellent model with which to elucidate the native immune responses that develop during tumor progression and to develop effective antitumor vaccine strategies.
A Review of Temporary Cardiac Pacing Wires

Aims This review aims to tabulate data from all available studies of temporary cardiac pacing wires. Particular aims were to determine the best route of venous access and find ways to reduce complications. The review set out to see if specialist doctors are better at inserting wires than non-specialist doctors. In addition, a contemporary study of wire insertion has been performed to compare modern practice in the UK with the previous studies. Methods A literature search produced 15 studies available for inclusion. Over 3700 patients from 1973 to 2004 were included. The data was tabulated and attention was given to the route of venous access, the complication rates and whether a specialist or non-specialist doctor had inserted the wire. Results Internal jugular veins are associated with lowest complication rates and ease of access. Antecubital fossa veins have the highest complication rates. Complication rates are high, especially infections and failure to secure access. Specialist doctors have lower rates of complications than non-specialist doctors. Elderly patient suffer the highest complication rate. Our study showed comparable results to the previous studies. Conclusion Internal jugular veins are the preferred route for access followed by subclavian and femoral veins. The right side should be used when possible. The use of antibiotics and ultrasound probes must be contemplated for all wire insertions. Alternatives to wire insertion (especially in the elderly) must be seriously considered. Setting up an on-call rota would provide experienced doctors to reduce complication rates.
Improved Inference in the Evaluation of Mutual Fund Performance Using Panel Bootstrap Methods

Two new methodologies are introduced to improve inference in the evaluation of mutual fund performance against benchmarks. First, the benchmark models are estimated using panel methods with both fund and time effects. Second, the non-normality of individual mutual fund returns is accounted for by using panel bootstrap methods. We also augment the standard benchmark factors with fund-specific characteristics, such as fund size. Using a dataset of UK equity mutual fund returns, we find that fund size has a negative effect on the average fund manager’s benchmark-adjusted performance. Further, when we allow for time effects and the non-normality of fund returns, we find that there is no evidence that even the best performing fund managers can significantly out-perform the augmented benchmarks after fund management charges are taken into account.
Advances in the Measurement of the Lense-Thirring Effect with Planetary Motions in the Field of the Sun

By processing more than 400 000 planetary observations of various types with the dynamical models of the EPM2006 ephemerides, E.V. Pitjeva recently estimated a correction to the canonical Newtonian-Einsteinian Venus' perihelion precession of − 0.0004 ± 0.0001 arcseconds per century. The prediction of general relativity for the Lense-Thirring precession of the perihelion of Venus is − 0.0003 arcseconds per century. It turns out that neither other mismodelled/unmodelled standard Newtonian/Einsteinian effects nor exotic ones, postulated to, for example, explain the Pioneer anomaly, may have caused the estimated extra-precession of the Venus orbit which, thus, can be reasonably attributed to the gravitomagnetic field of the Sun, not modelled in the routines of the EPM2006 ephemerides. However, it must be noted that the quoted error is the formal, statistical one; the realistic uncertainty might be larger. Future improvements of the inner planets' ephemerides, with the inclusion of the Messenger and Venus-Express tracking data, should further improve the accuracy and the consistency of such a test of general relativity which would also benefit from the independent estimation of the extra-precessions of the perihelia (and the nodes) by other teams of astronomers.
Global analysis of thermal tolerance and latitude in ectotherms

A tenet of macroecology is that physiological processes of organisms are linked to large-scale geographical patterns in environmental conditions. Species at higher latitudes experience greater seasonal temperature variation and are consequently predicted to withstand greater temperature extremes. We tested for relationships between breadths of thermal tolerance in ectothermic animals and the latitude of specimen location using all available data, while accounting for habitat, hemisphere, methodological differences and taxonomic affinity. We found that thermal tolerance breadths generally increase with latitude, and do so at a greater rate in the Northern Hemisphere. In terrestrial ectotherms, upper thermal limits vary little while lower thermal limits decrease with latitude. By contrast, marine species display a coherent poleward decrease in both upper and lower thermal limits. Our findings provide comprehensive global support for hypotheses generated from studies at smaller taxonomic subsets and geographical scales. Our results further indicate differences between terrestrial and marine ectotherms in how thermal physiology varies with latitude that may relate to the degree of temperature variability experienced on land and in the ocean.