Miracle-dz/UniFAR-FTUs huggingface dataset:
CrossTalk proposal: Most of the cardiovascular consequences of OSA are due to increased sympathetic activity

There is clearly an association between obstructive sleep apnoea (OSA) and vascular disease (Marin et al. 2005; Gottlieb et al. 2010). Much vascular disease remains unexplained even after allowing for well-known risk factors, such as hypertension and dyslipidaemia (Jackson et al. 2009) and, because OSA is common, it certainly could provide a significant extra contribution. In recent years several potential hypotheses have been advanced to link OSA with vascular disease, derived from the complex physiological changes that actually occur during OSA (Kohler & Stradling, 2010), and supported by animal models and laboratory-based studies; these include intermittent hypoxia, intermittent arousal from sleep and increased intrathoracic pressure swings. The link between these consequences of OSA and vascular disease are probably multifactorial, most likely augmented sympathetic activity, with less evidence for oxidative stress, systemic inflammation, and vibration damage to the carotid arteries. However, because of the close association between central obesity and both OSA (Davies et al. 1992) and vascular disease (Yusuf et al. 2005), it has been very difficult to disentangle the inter-relations and demonstrate that OSA is a truly independent risk factor for vascular disease. Although laboratory studies may support plausible hypotheses, this does not prove their relevance to clinical medicine, a painful lesson learnt in other areas of vascular risk (e.g. anti-oxidant treatment and hormone replacement therapy) where plausible hypotheses, based on laboratory experiments and cross-sectional studies, failed to be supported by randomised controlled trials (RCTs; Simon et al. 2001; Lawlor et al. 2004). Therefore, studies of robust design, allowing identification of true causality, are essential in this area. Each of the above-mentioned mechanisms that possibly underpin the association between OSA and vascular disease needs to be proven to be clinically relevant in RCTs. At present such data are most supportive for increased sympathetic nervous system activity, which appears more than adequate as a mechanism to explain the associations observed between OSA and vascular disease.
Use of Whole-Blood Samples in In-House Bulk and Single-Cell Antigen-Specific Gamma Interferon Assays for Surveillance of Mycobacterium tuberculosis Infections

ABSTRACT Tests based on the gamma interferon (IFN-γ) assay (IGA) are used as adjunctive tools for the diagnosis of Mycobacterium tuberculosis infection. Here we compared in-house and commercial whole-blood IGAs to identify a suitable assay for the surveillance of tuberculosis in population studies. The IGAs were selected on the basis of the ease with which they are performed and because they require a small amount of a biological sample and do not require cell purification. Since a “gold standard” for latently M. tuberculosis-infected individuals is not available, the sensitivities and the specificities of the IGAs were determined with samples from patients with clinically diagnosed active tuberculosis and in Mycobacterium bovis BCG-unvaccinated healthy controls. The in-house tests consisted of a bulk assay based on diluted whole blood and a single-cell assay based on IFN-γ intracellular staining. The commercial assays used were the QuantiFERON-TB-Gold (Q-TB) and the Q-TB in-tube tests. When the purified protein derivative was used as the antigen, in-house whole-blood intracellular staining was found to be highly discriminatory between active tuberculosis patients and BCG-vaccinated healthy controls, whereas the other IGAs did not discriminate between the two categories of patients. When M. tuberculosis-specific antigens were used, a very strong agreement between the results of the Q-TB in-tube assay and the clinical diagnosis was observed, while the Q-TB assay, performed according to the manufacturer's instructions, showed a significantly lower performance. Intriguingly, when the test was performed with RD1 proteins instead of peptides, its sensitivity was significantly increased. The in-house assay with diluted whole blood showed an elevated sensitivity and an elevated specificity, and the results agreed with the clinical diagnosis. Considering that the in-house assay uses 1/20 of the sample compared with the amount of sample used in the commercial IGA, it appears to be particularly promising for use in pediatric studies. Overall, the different assays showed different performance characteristics that need to be considered for surveillance of tuberculosis in population studies.
Preparation and Characterization of Immunogen for Monoclonal antibody production against infectious bursal disease virus serotype 1 of poultry

Infectious bursal disease (IBD), defined as a list B disease by the Office International des Epizootics (OIE), caused by IBD virus of birnaviridae, shows antigenic variation and recently very virulent field isolates have been identified in U.S.A. and European countries. Monoclonal antibodies (MAbs) are valuable tools in characterizing virion's antigenic sites and detecting antigenic variation. Preparation of immunogen is one of the initial hurdles of MAb production against a virus. The present study was undertaken with the objective to produce suitable IBD virus immunogen for production of MAbs. For this a field isolate of IBD virus was adapted to chick embryo fibroblast (CEF) culture and the virus produced in bulk was partially purified by polyethylene glycol precipitation and trichloro-trifluoro ethane (Freon) extraction followed by discontinuous sucrose gradient (60 and 30%) ultracentifugation. The partially purified virus was confirmed by AGPT, virus neutralization test and characterized by SDS-PAGE analysis and then used as immunogen for inmmnizing the Balb/c mice. The splenocytes obtained from the immunized mice were used for producing hybridoma and then the hybridoma colonies were screened by indirect ELISA for secretion ofIBDV specific antibodies. A 23.2% (26 out of 112 hybridoma colonies screened) positive hybridoma colonies specific for IBD virus were obtained in one ofthe hybridization experiments. The relatively high percentage of IBD virus specific hybridomas obtained might be due to immunization of the mice with purified IBD virus antigen, which was propagated in CEF culture. The CEF culture system is advantageous as the purification is easier and at the same time it is a homologous system for IBD virus propagation.
Data-driven Natural Language Generation: Paving the Road to Success

We argue that there are currently two major bottlenecks to the commercial use of statistical machine learning approaches for natural language generation (NLG): (a) The lack of reliable automatic evaluation metrics for NLG, and (b) The scarcity of high quality in-domain corpora. We address the first problem by thoroughly analysing current evaluation metrics and motivating the need for a new, more reliable metric. The second problem is addressed by presenting a novel framework for developing and evaluating a high quality corpus for NLG training.
Formation of the Orientale lunar multiring basin

titOn the origin of Orientale basinle Orientale basin is a major impact crater on the Moon, which is hard to see from Earth because it is right on the western edge of the lunar nearside. Relatively undisturbed by later events, Orientale serves as a prototype for understanding large impact craters throughout the solar system. Zuber et al. used the Gravity Recovery and Interior Laboratory (GRAIL) mission to map the gravitational field around the crater in great detail by flying the twin spacecraft as little as 2 km above the surface. Johnson et al. performed a sophisticated computer simulation of the impact and its subsequent evolution, designed to match the data from GRAIL. Together, these studies reveal how major impacts affect the lunar surface and will aid our understanding of other impacts on rocky planets and moons. Science, this issue pp. 438 and 441 Simulations of the formation of the Orientale basin on the Moon reveal the origin of its multiple rings Multiring basins, large impact craters characterized by multiple concentric topographic rings, dominate the stratigraphy, tectonics, and crustal structure of the Moon. Using a hydrocode, we simulated the formation of the Orientale multiring basin, producing a subsurface structure consistent with high-resolution gravity data from the Gravity Recovery and Interior Laboratory (GRAIL) spacecraft. The simulated impact produced a transient crater, ~390 kilometers in diameter, that was not maintained because of subsequent gravitational collapse. Our simulations indicate that the flow of warm weak material at depth was crucial to the formation of the basin’s outer rings, which are large normal faults that formed at different times during the collapse stage. The key parameters controlling ring location and spacing are impactor diameter and lunar thermal gradients.
Phosphorylation of IP3R1 and the regulation of [Ca2+]i responses at fertilization: a role for the MAP kinase pathway

A sperm-induced intracellular Ca2+ signal ([Ca2+]i) underlies the initiation of embryo development in most species studied to date. The inositol 1,4,5 trisphosphate receptor type 1 (IP3R1) in mammals, or its homologue in other species, is thought to mediate the majority of this Ca2+ release. IP3R1-mediated Ca2+ release is regulated during oocyte maturation such that it reaches maximal effectiveness at the time of fertilization, which, in mammalian eggs, occurs at the metaphase stage of the second meiosis (MII). Consistent with this, the [Ca2+]i oscillations associated with fertilization in these species occur most prominently during the MII stage. In this study, we have examined the molecular underpinnings of IP3R1 function in eggs. Using mouse and Xenopus eggs, we show that IP3R1 is phosphorylated during both maturation and the first cell cycle at a MPM2-detectable epitope(s), which is known to be a target of kinases controlling the cell cycle. In vitro phosphorylation studies reveal that MAPK/ERK2, one of the M-phase kinases, phosphorylates IP3R1 at at least one highly conserved site, and that its mutation abrogates IP3R1 phosphorylation in this domain. Our studies also found that activation of the MAPK/ERK pathway is required for the IP3R1 MPM2 reactivity observed in mouse eggs, and that eggs deprived of the MAPK/ERK pathway during maturation fail to mount normal [Ca2+]i oscillations in response to agonists and show compromised IP3R1 function. These findings identify IP3R1 phosphorylation by M-phase kinases as a regulatory mechanism of IP3R1 function in eggs that serves to optimize [Ca2+]i release at fertilization.
Signals and assessment in African elephants: evidence from playback experiments

A series of playback experiments using two elephant vocalizations, the 'musth rumble' and the 'oestrous call', was carried out in Amboseli National Park to examine signalling and assessment in African elephants, Loxodonta africana. In response to the musth rumble of a high-ranking male other musth males approached the speaker aggressively, whereas nonmusth males walked away from the stimulus. The call of an oestrous female, too, attracted musth males who approached the speaker rapidly, while nonmusth males listened and then walked away. Females listened and often showed considerable interest in the musth rumbles of males, approaching the speaker and sometimes responding by vocalizing and or secreting from the temporal glands. The experiments bear out earlier observational data and game theory predictions which suggest that by being in or out of musth a male may be conveying information about the relative value he places on contesting his dominance rank and his access to oestrous females. When not visibly in musth, a male may be indicating his intention not to contest access to oestrous females. Copyright 1999 The Association for the Study of Animal Behaviour.
Actin Microfilaments Facilitate the Retrograde Transport from the Golgi Complex to the Endoplasmic Reticulum in Mammalian Cells

The morphology and subcellular positioning of the Golgi complex depend on both microtubule and actin cytoskeletons. In contrast to microtubules, the role of actin cytoskeleton in the secretory pathway in mammalian cells has not been clearly established. Using cytochalasin D, we have previously shown that microfilaments are not involved in the endoplasmic reticulum–Golgi membrane dynamics. However, it has been reported that, unlike botulinum C2 toxin and latrunculins, cytochalasin D does not produce net depolymerization of actin filaments. Therefore, we have reassessed the functional role of actin microfilaments in the early steps of the biosynthetic pathway using C2 toxin and latrunculin B. The anterograde endoplasmic reticulum‐to‐Golgi transport monitored with the vesicular stomatitis virus‐G protein remained unaltered in cells treated with cytochalasin D, latrunculin B or C2 toxin. Conversely, the brefeldin A‐induced Golgi membrane fusion into the endoplasmic reticulum, the Golgi‐to‐endoplasmic reticulum transport of a Shiga toxin mutant form, and the subcellular distribution of the KDEL receptor were all impaired when actin microfilaments were depolymerized by latrunculin B or C2 toxin. These findings, together with the fact that COPI‐coated and uncoated vesicles contain β/γ‐actin isoforms, indicate that actin microfilaments are involved in the endoplasmic reticulum/Golgi interface, facilitating the retrograde Golgi‐to‐endoplasmic reticulum membrane transport, which could be mediated by the orchestrated movement of transport intermediates along microtubule and microfilament tracks.
The Correlation of Comorbidity with Function of the Shoulder and Health Status of Patients Who Have Glenohumeral Degenerative Joint Disease*

We studied the effect of comorbidities on function of the shoulder and health status in a group of eighty-five consecutive patients who had glenohumeral degenerative joint disease of sufficient severity to meet one surgeon's criteria for the performance of shoulder arthroplasty. A questionnaire was used to identify the comorbidities, such as other diseases, social factors, or a work-related injury, for each patient. The number of functions on the Simple Shoulder Test that the patient could perform had a significant negative correlation with the number of comorbidities (r = -0.32, intercept = 4.6 per cent, slope = -0.6, and p = 0.0031). Each parameter on the Short Form-36 (except for physical role function) had a significant negative correlation with the number of comorbidities (p < 0.05). This negative relationship was strongest for general health perception (r = -0.42) and vitality (r = -0.35). We concluded that the number of comorbidities has a quantitative effect on function of the shoulder. In the evaluation of the functional status of patients and the effectiveness of treatment, the effects of comorbidity must be controlled. The results of the present study demonstrate that the scores on the Short Form-36 are quantitatively related to the number of comorbidities. The six parameters that are unrelated to function of the shoulder (physical function, social function, emotional role function, mental health, vitality, and general health perception) may provide a practical way to integrate the effects of all potential comorbidities on individual patients. Future clinical research will be strengthened by efforts to measure the impact of comorbidities and by strategies to control for their effects.
The Adoption of Web 2.0 in Corporations: A Process Perspective

Widely discussed in the media, Web 2.0 systems have drawn the attention of corporations, many of which now seek to adopt Web 2.0 technologies and transfer its benefits to their organizations. Organizations often struggle with the adoption of information systems, and Web 2.0 systems are certainly no exception. As an empirical foundation, we studied three organizations that successfully adopted Web 2.0 systems. We conducted a narrative analysis of the case study material to produce a process theory for Web 2.0 system adoption. Finally, we compare it to the enterprise system experience cycle of Markus and Tanis (2000). Our results indicate that the adoption of Web 2.0 systems differs from larger enterprise system adoption projects. This is rooted in the lower implementation and maintenance costs as well as lower technical complexity of Web 2.0 systems. Furthermore, its voluntary characteristics lead to an adoption process that focuses mainly on convincing users of its benefits.
Intrinsic and acquired resistance to methotrexate in acute leukemia.

Methotrexate, a folic acid antagonist, is used extensively not only for the treatment of cancer but also for the treatment of rheumatoid arthritis, psoriasis, and autoimmune disease and for the prevention of graft-versus-host disease after transplantation. The drug is also used as an abortifacient.1,2 Other folate antagonists are used to treat bacterial infections (trimethoprim), malaria (pyrimethamine), and Pneumocystis carinii infection (trimetrexate with leucovorin). 3,4 As with other drugs used to treat infectious diseases or cancers, the development of resistance limits the effectiveness of these folate antagonists. An understanding of the mechanisms of resistance to this class of drugs is .
Advanced photochemical oxidation of emergent micropollutants: Carbamazepine

The combination of UV radiation with hydrogen peroxide has been widely used for the photodegradation of pollutants in aqueous solutions. Statistical design of experiments is a powerful tool to optimize this kind of process. Initial hydrogen peroxide concentration, pH and temperature were considered as the variables for the process optimization. The interactions existing between these three variables were analyzed. Initial concentration of hydrogen peroxide proved to be the most important variable conditioning the removal efficiency, followed by temperature, and pH shows a non-significant positive influence along the whole operation interval. The ANOVA test reported significance for five of the nine involved variables. The Response Surface Methodology technique was used to optimize carbamazepine degradation. Under optimal conditions (hydrogen peroxide concentration = 0.38·10−3 mol L−1, pH = 1 and temperature = 35.6°C) total carbamazepine degradation was achieved.
Significance of meaning in sound quality evaluation

There is agreement that perceptually-adequate sound evaluation has to encompass not only the sensory domain but also cognitive and emotional variables [1]. In particular, the meaning of a sound has been identified as an important factor which may include effects of attitude, prior experience, and user expectations. Further, it is assumed that the effects of meaning are mediated through the prior identification of the sound source in the listening process.
A minimal base‐pairing region of a bacterial small RNA SgrS required for translational repression of ptsG mRNA

Escherichia coli SgrS is an Hfq‐binding small RNA that is induced under glucose‐phosphate stress to cause translational repression and RNase E‐dependent rapid degradation of ptsG mRNA encoding the major glucose transporter. A 31‐nt‐long stretch in the 3′ region of SgrS is partially complementary to the translation initiation region of ptsG mRNA. We showed previously that SgrS alone causes translational repression when pre‐annealed with ptsG mRNA by a high‐temperature treatment in vitro. Here, we studied translational repression of ptsG mRNA in vitro by synthetic RNA oligonucleotides (oligos) to define the SgrS region required for translational repression. We first demonstrate that a 31 nt RNA oligo corresponding to the base‐pairing region is sufficient for translational inhibition of ptsG mRNA. Then, we show that RNA oligo can be shortened to 14 nt without losing its effect. Evidence shows that the 14 nt base‐pairing region is sufficient to inhibit ptsG translation in the context of full‐length SgrS in vivo. We conclude that SgrS 168–181 is a minimal base‐pairing region for translational inhibition of ptsG mRNA. Interestingly, the 14 nt oligo efficiently inhibited ptsG translation without the high‐temperature pre‐treatment, suggesting that remodelling of structured SgrS is an important mechanism by which Hfq promotes the base pairing.
Single inertialization of a 2-inertia system based on fine torsional torque and sensor-based resonance ratio controllers

This paper achieves “single inertialization” of a 2-inertia resonant system by using a I-P-I-P torsional torque controller and a torque-sensor-based resonance ratio controller(RRC). Since the torsional torque controller with the RRC changes the dynamics between the torque reference and the actual torsional torque into a series connection system of a second order low pass filter(LPF), the 2-inertia resonant system is able to be regarded as a fourth order LPF and a single inertia system. Furthermore, this paper theoretically derives the I-P-I-P controller gain and the resonance ratio gain for suppressing effectively the resonant vibration. The simulation results confirm the effectiveness, and verify the control responses against the parameter variation. By using the single inertialization, general control systems developed for a single inertia system are able to be applied to a 2-inertia resonant system.
Clinical value of a new TSH binding inihibitory activity assay using human TSH receptors in the follow‐up of antithyroid drug treated Graves' disease. Comparison with thyroid stimulating antibody bioassay

First, to evaluate the performance level of a new TSH binding inhibitory antibody assay using human recombinant TSH receptors (h‐TBII) in comparison with a thyroid stimulating antibody (TSAb) bioassay performed before, at the end of treatment (18 months) and after antithyroid drug withdrawal in Graves' disease patients; second, to assess the accuracy with which h‐TBII levels could predict relapse and remission.
Use of monoclonal antibodies in oncology.

Humera Khurshid, MD, and Natalie Sinclair, MD  Monoclonal antibodies (Mca) represent a significant addition to therapeutic options for a number of oncologic disorders. MCA are highly specific. They bind to and affect disease specific targets resulting in sparing of normal cells with less side effects than traditional chemotherapy. This review focuses on MCA approved for clinical use. MCA are produced by a single clone of B cells and are mono specific. These antibodies can block essential cellular receptors, directly induce apoptosis, bind to target cells, and recruit antibodydependant cellular or complement-dependent cytotoxicity mechanisms. They can also deliver cytotoxic chemicals such as radioisotopes and toxins. The pharmacologic characteristics are summarized. [Table 1] The Food and Drug Administration (FDA) has approved several MCA for oncologic indications.
Bayesian Accelerated Failure Time Model With Multivariate Doubly Interval-Censored Data and Flexible Distributional Assumptions

In this article we consider the relationship of covariates to the time to caries of permanent first molars. This involves an analysis of multivariate doubly interval-censored data. To describe this relationship, we suggest an accelerated failure time model with random effects, taking into account that the observations are clustered. Indeed, up to four permanent molars per child enter into the analysis, implying up to four caries times for each child. Each distributional part of the model is specified in a flexible way as a penalized Gaussian mixture with an overspecified number of mixture components. A Bayesian approach with the Markov chain Monte Carlo methodology is used to estimate the model parameters, and a software package in the R language has been written that implements it.