Miracle-dz/UniFAR-FTUs huggingface dataset:
Selective Degradation of Host RNA Polymerase II Transcripts by Influenza A Virus PA-X Host Shutoff Protein

Influenza A viruses (IAVs) inhibit host gene expression by a process known as host shutoff. Host shutoff limits host innate immune responses and may also redirect the translation apparatus to the production of viral proteins. Multiple IAV proteins regulate host shutoff, including PA-X, a ribonuclease that remains incompletely characterized. We report that PA-X selectively targets host RNA polymerase II (Pol II) transcribed mRNAs, while sparing products of Pol I and Pol III. Interestingly, we show that PA-X can also target Pol II-transcribed RNAs in the nucleus, including non-coding RNAs that are not destined to be translated, and reporter transcripts with RNA hairpin structures that block ribosome loading. Transcript degradation likely occurs in the nucleus, as PA-X is enriched in the nucleus and its nuclear localization correlates with reduction in target RNA levels. Complete degradation of host mRNAs following PA-X-mediated endonucleolytic cleavage is dependent on the host 5’->3’-exonuclease Xrn1. IAV mRNAs are structurally similar to host mRNAs, but are synthesized and modified at the 3’ end by the action of the viral RNA-dependent RNA polymerase complex. Infection of cells with wild-type IAV or a recombinant PA-X-deficient virus revealed that IAV mRNAs resist PA-X-mediated degradation during infection. At the same time, loss of PA-X resulted in changes in the synthesis of select viral mRNAs and a decrease in viral protein accumulation. Collectively, these results significantly advance our understanding of IAV host shutoff, and suggest that the PA-X causes selective degradation of host mRNAs by discriminating some aspect of Pol II-dependent RNA biogenesis in the nucleus.
Structural and Functional Relationships in Glaucoma Using Standard Automated Perimetry and the Humphrey Matrix

Purpose To evaluate and compare correlations between structural and functional loss in glaucoma as assessed by optical coherence tomography (OCT), scanning laser polarimetry (GDx VCC, as this was the model used in this study), standard automated perimetry (SAP), and the Humphrey Matrix (Matrix). Methods Ninety glaucomatous eyes identified with SAP and 112 eyes diagnosed using Matrix were independently classified into six subgroups, either S1/M1 (MD>-6dB), S2/M2 (-12<MD<-6dB) or S3/M3 (MD<-12dB), according to the mean deviation (MD) of each test. Average and sectoral retinal nerve fiber layer (RNFL) thickness and percentage of abnormal classifications using the internal normative databases of OCT and GDx VCC were compared among the six subgroups. Results In the SAP subgroups, RNFL thickness values obtained by OCT in the nasal and temporal quadrants and the inferior averages of GDx VCC did not differ between the S1 and S2 subgroups (p=0.137, 0.738 and 0.149, respectively). In the Matrix subgroups, no measurement parameters differed between the M1 and M2 groups except for the overall mean and average inferior RNFL thickness given by OCT and the NFI values of GDx VCC (p=0.013, 0.016 and 0.029, respectively). When abnormal classifications were compared, all measurement parameters, without exception, were significantly different in both the SAP and the Matrix subgroups. Conclusions SAP subgroups showed a good correlation of structural and functional defects when assessed using OCT and GDx VCC. These correlations were weaker in the Matrix subgroups, especially in the early stages of glaucoma.
The Contribution of Immune and Glial Cell Types in Experimental Autoimmune Encephalomyelitis and Multiple Sclerosis

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system characterised by widespread areas of focal demyelination. Its aetiology and pathogenesis remain unclear despite substantial insights gained through studies of animal models, most notably experimental autoimmune encephalomyelitis (EAE). MS is widely believed to be immune-mediated and pathologically attributable to myelin-specific autoreactive CD4+ T cells. In recent years, MS research has expanded beyond its focus on CD4+ T cells to recognise the contributions of multiple immune and glial cell types to the development, progression, and amelioration of the disease. This review summarises evidence of T and B lymphocyte, natural killer cell, macrophage/microglial, astrocytic, and oligodendroglial involvement in both EAE and MS and the intercommunication and influence of each cell subset in the inflammatory process. Despite important advances in the understanding of the involvement of these cell types in MS, many questions still remain regarding the various subsets within each cell population and their exact contribution to different stages of the disease.
[Ketamine and preemptive analgesia.].

UNLABELLED BACKAGROUND AND OBJECTIVES: Since the finding that ketamine blocks NMDA receptors in the neurons of spinal dorsal horn, it has been used to inhibit or decrease central sensitization triggered by nociceptive stimulations. This study aimed at presenting pharmacological aspects of racemic ketamine and its levogyrous compound, as well as its usefulness for preemptive analgesia. CONTENTS Current preemptive analgesia concepts, pharmacological aspects of ketamine and its levogyrous compound, as well as experimental and clinical trials on ketamine and its use in preemptive analgesia are presented. CONCLUSIONS The efficacy of ketamine in inhibiting or decreasing central sensitization triggered by nociceptive stimulations is not totally confirmed, probably due to different study and statistical analysis methods.
Mobility-aware Ant Colony Optimization routing for vehicular ad hoc networks

Vehicular Ad hoc Networks (VANETs) are a special type of Mobile Ad hoc Networks (MANETs), made by vehicles communicating among themselves, and by vehicles communicating to devices located in the margins of roads and highways. The main characteristic of a VANET is the high speed of network nodes – that can go up to 200 km/h –, and that impacts directly on the ability the network has to deliver data, given we might have a network formed for just a small amount of time. It has been shown in several works that ant-based routing can be successfully applied to both wired and wireless networks. This work proposes Ant Colony Optimization (ACO) procedures that take advantage of information available in vehicular networks – such as the vehicles' position and speed –, in order to design an ant-based algorithm that performs well in the dynamics of such networks. The authors have also adapted the Dynamic MANET On-demand (DYMO) routing protocol to make use of the ACO procedures proposed in this paper, and the resulting bio-inspired protocol, MAR-DYMO, had its performance evaluated in an urban scenario and compared against a few other routing protocols. The obtained results suggest that making use of environmental information can make ACO algorithms more suitable for routing in vehicular ad hoc networks.
PPAR-γ Ligands Repress TGFβ-Induced Myofibroblast Differentiation by Targeting the PI3K/Akt Pathway: Implications for Therapy of Fibrosis

Transforming growth factor beta (TGFβ) induced differentiation of human lung fibroblasts to myofibroblasts is a key event in the pathogenesis of pulmonary fibrosis. Although the typical TGFβ signaling pathway involves the Smad family of transcription factors, we have previously reported that peroxisome proliferator-activated receptor-γ (PPAR-γ) ligands inhibit TGFβ-mediated differentiation of human lung fibroblasts to myofibroblasts via a Smad-independent pathway. TGFβ also activates the phosphatidylinositol 3 kinase/protein kinase B (PI3K/Akt) pathway leading to phosphorylation of AktS473. Here, we report that PPAR-γ ligands, 2-cyano-3,12-dioxooleana-1,9-dien-28-oic acid (CDDO) and 15-deoxy-(12,14)-15d-prostaglandin J2 (15d-PGJ2), inhibit human myofibroblast differentiation of normal and idiopathic pulmonary fibrotic (IPF) fibroblasts, by blocking Akt phosphorylation at Ser473 by a PPAR-γ-independent mechanism. The PI3K inhibitor LY294002 and a dominant-negative inactive kinase-domain mutant of Akt both inhibited TGFβ-stimulated myofibroblast differentiation, as determined by Western blotting for α-smooth muscle actin and calponin. Prostaglandin A1 (PGA1), a structural analogue of 15d-PGJ2 with an electrophilic center, also reduced TGFβ-driven phosphorylation of Akt, while CAY10410, another analogue that lacks an electrophilic center, did not; implying that the activity of 15d-PGJ2 and CDDO is dependent on their electrophilic properties. PPAR-γ ligands inhibited TGFβ-induced Akt phosphorylation via both post-translational and post-transcriptional mechanisms. This inhibition is independent of MAPK-p38 and PTEN but is dependent on TGFβ-induced phosphorylation of FAK, a kinase that acts upstream of Akt. Thus, PPAR-γ ligands inhibit TGFβ signaling by affecting two pro-survival pathways that culminate in myofibroblast differentiation. Further studies of PPAR-γ ligands and small electrophilic molecules may lead to a new generation of anti-fibrotic therapeutics.
Drawing the Line: How People with Autism Copy Line Drawings of Three-Dimensional Objects

It is purported that the local perceptual style characteristic of those with autism results in them reproducing line drawings in a more localised manner than comparison individuals. Here we report an exception to this: the drawing strategies of those with autism were more global. When reproducing line drawings depicting three-dimensional objects, a sample of fifty-six participants with autism showed a greater tendency to begin by copying the two-dimensional outline of the figure than fifty-seven matched comparison participants (39.3% versus 8.8% of group; χ21 = 14.46, p < 0.0005). We argue that this is consistent with the perception of those with autism being less conceptually driven, but not necessarily less global.
Auctions vs. Bookbuilding and the Control of Underpricing in Hot IPO Markets

Market returns before the offer price is set affect the amount and variability of initial public offering (IPO) underpricing. Thus an important question is "What IPO procedure is best adapted for controlling underpricing in "hot" versus "cold" market conditions? " The French stock market offers a unique arena for empirical research on this topic, since three substantially different issuing mechanisms (auctions, bookbuilding, and fixed price) are used there. Using 1992--1998 data, we find that the auction mechanism is associated with less underpricing and lower variance of underpricing. We show that the auction procedure's ability to incorporate more information from recent market conditions into the IPO price is an important reason. Copyright 2003, Oxford University Press.
Cigarette Smoke Disturbs the Survival of CD8+ Tc/Tregs Partially through Muscarinic Receptors-Dependent Mechanisms in Chronic Obstructive Pulmonary Disease

Background CD8+ T cells (Cytotoxic T cells, Tc) are known to play a critical role in the pathogenesis of smoking related airway inflammation including chronic obstructive pulmonary disease (COPD). However, how cigarette smoke directly impacts systematic CD8+ T cell and regulatory T cell (Treg) subsets, especially by modulating muscarinic acetylcholine receptors (MRs), has yet to be well elucidated. Methods Circulating CD8+ Tc/Tregs in healthy nonsmokers (n = 15), healthy smokers (n = 15) and COPD patients (n = 18) were evaluated by flow cytometry after incubating with anti-CD3, anti-CD8, anti-CD25, anti-Foxp3 antibodies. Peripheral blood T cells (PBT cells) from healthy nonsmokers were cultured in the presence of cigarette smoke extract (CSE) alone or combined with MRs agonist/antagonist for 5 days. Proliferation and apoptosis were evaluated by flow cytometry using Ki-67/Annexin-V antibodies to measure the effects of CSE on the survival of CD8+ Tc/Tregs. Results While COPD patients have elevated circulating percentage of CD8+ T cells, healthy smokers have higher frequency of CD8+ Tregs. Elevated percentages of CD8+ T cells correlated inversely with declined FEV1 in COPD. CSE promoted the proliferation and inhibited the apoptosis of CD8+ T cells, while facilitated both the proliferation and apoptosis of CD8+ Tregs. Notably, the effects of CSE on CD8+ Tc/Tregs can be mostly simulated or attenuated by muscarine and atropine, the MR agonist and antagonist, respectively. However, neither muscarine nor atropine influenced the apoptosis of CD8+ Tregs. Conclusion The results imply that cigarette smoking likely facilitates a proinflammatory state in smokers, which is partially mediated by MR dysfunction. The MR antagonist may be a beneficial drug candidate for cigarette smoke-induced chronic airway inflammation.
Ultimate Ownership Structure and Bank Regulatory Capital Adjustment: Evidence from European Commercial Banks

This paper empirically investigates whether a bank's decision to adjust its capital is influenced by the existence of a divergence between the voting and the cash-flow rights of its ultimate owner. We use a novel hand-collected dataset on detailed control and ownership characteristics of 405 European commercial banks to estimate an ownership-augmented capital adjustment model over the 2003-2010 period. We find no differences in adjustment speeds when banks need to adjust their Tier 1 capital downwards to reach their target capital ratio. However, when the adjustment process requires an upward shift in Tier 1 capital, the adjustment is significantly slower for banks controlled by a shareholder with a divergence between voting and cash-flow rights. Further investigation shows that such an asymmetry only holds if the ultimate owner is a family or a state or if the bank is headquartered in a country with relatively weak shareholder protection. Moreover, this behavior is tempered during the 2008 financial crisis, possibly because of government capital injections or support from ultimate owners (propping up). Our findings provide new insights for understanding capital adjustment in general and have policy implications on the road to the final stage of Basel III in 2019.
The Region of Achievable Rates for Multiterminal Source Coding--Part I

It is proved that a convexified form of the Berger-Tung inner b ound provides the set of all achievable rates for the multiterminal source coding problem. In this p aper, a proof is developed for general discrete memoryless sources and bounded distortion measures, for tw o encoding terminals. The proof is based on two new developments. One is the construction of new inner an d outer bounds to the rate region, with the property that both are defined over the same class of probabil ity distributions, thus making them directly comparable. Another is a series of lemmas about properties o f covers induced by generic distributed codes, which show that Berger-Tung codes induce covers of maximum s ize. This result constitutes a solution to an open problem in network information theory, whose formulat ion dates back to at least 1973.
Potential Asymmetries in Language Comprehension : In Search of the Electrical Right

Several different brain areas, including cortical regions in both hemispheres, contribute to language comprehension and production. This is not surprising given that a large number of brain areas are involved in cognitive tasks thought to be less complex than language, and that language comprises many different computations subserved by different neural substrates. For these reasons, it has proven difficult to give a satisfactory answer to the question of what specific contributions the right hemisphere makes to language processing. A completely satisfying account presupposes that we know what language is, the dynamics of language processing, and the intricacies of how these processes are knit into neural tissue. Therefore, we expect that the reader will be left somewhat unsatisfied, although excited by the possibility that electrophysiological data will ultimately help resolve the answer more clearly. In this chapter, we show that patterns of voltage recorded from either the scalp or the cortical surface can highlight differences in the dynamics of the contributions of regions in the two hemispheres, but cannot be taken as signs of some absolute level of hemispheric contribution to processing. Nor do differences in hemispheric contribution necessarily reflect some neat dichotomy; those who seek grand differences between the hemispheres will soon discover that the left and the right, like the warp and the weft of the cloth, are both made of silk. The same might be said about the differences between linguistic and nonlinguistic processing independent of the issues surrounding laterality. The tapestry of language is remarkable in that so much of the fabric is woven from threads of perception and cognition and scraps of motoric processing. We fear that
Exploiting Human Memory B Cell Heterogeneity for Improved Vaccine Efficacy

The major goal in vaccination is establishment of long-term, prophylactic humoral memory to a pathogen. Two major components to long-lived humoral memory are plasma cells for the production of specific immunoglobulin and memory B cells that survey for their specific antigen in the periphery for later affinity maturation, proliferation, and differentiation. The study of human B cell memory has been aided by the discovery of a general marker for B cell memory, expression of CD27; however, new data suggests the existence of CD27− memory B cells as well. These recently described non-canonical memory populations have increasingly pointed to the heterogeneity of the memory compartment. The novel B memory subsets in humans appear to have unique origins, localization, and functions compared to what was considered to be a “classical” memory B cell. In this article, we review the known B cell memory subsets, the establishment of B cell memory in vaccination and infection, and how understanding these newly described subsets can inform vaccine design and disease treatment.
One Quarter of GDP Is Persuasion

Economists view talk as cheap and culture as insignificant. Yet humans are talking animals, talking in their markets. The talk probably matters: why else would the human animals bother doing it? The usual economic view of the talk is that it issues orders and conveys information. Workers at GM are ordered to report for work tomorrow; credit ratings are conveyed. Economic analysis takes these parts of the talk into account without fuss. Production theory can be viewed as the theory of one mind issuing orders. Much of game theory is concerned in one way or another with information (though game theory, as Joseph Farrell (1995) and others have found, requires more than bits of information). But issuing the orders and conveying the information does not account for all of the talk. The third part of the economic talk is persuasion.
The social organisation of learning difficulties at university : a qualitative study of four Higher Education Institutions in the North East Region of England

The last decades there is a clear shift in people’s attitudes towards disability and the participation of disabled people in society and especially in education. The new disability law and the anti-discrimination legislation changed the relationship between disabled students and Higher Education, allowing them access and providing support for their needs. The current research aims to discuss support and provision for students with learning difficulties within Higher Education Institutions. Specifically, within the framework of North East Universities in England (Newcastle University, Northumbria University, Durham and Sunderland University) the research addresses the issues around provision for students with learning difficulties at Durham University. The experiences of the students themselves, as well as the views of the Directors of the Disability Support Unit (DSU) from all four universities combined with the perspectives of lecturers and College Officers from Durham University only, they create a framework within which support and provision are discussed. This project used qualitative methodology as it was considered appropriate for the nature of the research problem. Semi-structured interviews were used for the data collection and were combined with the secondary literature (such as journal articles, papers, websites, documents provided by the institutions etc) to draw a more complete picture of the issues of interest. In the end, the sample consisted of 18 students with learning difficulties who studied in the four Higher Education Institutions, 4 interviews with the Directors of the DSUs from these universities and 7 interviews with lecturers and college officers from Durham University only. Clearly, from the findings of the project some of the changes in Higher Education are steps towards an inclusive educational environment where the needs of all students will be taken care of, regardless of disabilities or abilities of students. However, there are still concerns, which were expressed from both students and Directors of DSUs, about ‘attitudinal barriers’, which are necessary to change, in order to achieve the inclusive education for all. The research also concluded that in order to achieve an all-inclusive educational system it is necessary to focus more on personalised services and treatment for students with learning difficulties, where all the individual needs of students are met. The bureaucratisation of the services and the turn of the education towards marketisation where institutions compete for students and promote the market behaviour have to be replaced by personalisation in services and support for disabled students.
A Mapping Survey of the 13CO and 12CO Emission in Galaxies

We present spectra of the extended 12CO and 13CO J = 1 → 0 emission along the major axes of 17 nearby galaxies. Spatial variations in the ratio of CO and 13CO integrated intensities, ℛ, are found in nearly every galaxy observed. There is an overall variation in ℛ of 20%-40% from the inner 2 kpc to the disk. Roughly one-third of the survey galaxies have such gradients in ℛ detected above the 2 σ confidence level. Though some galaxies show a lower central value of ℛ, on average ℛ inside 2 kpc is 10%-30% higher than ℛ outside of 2 kpc. The average CO/13CO intensity ratio within the central 2 kpc of the survey sources is 11.6 ± 0.4 (based on the noise) ± 1.5 (based on systematic uncertainties estimated from daily variations in CO and 13CO intensities). The 1 σ dispersion in ℛ between galactic nuclei of 4.2 is also quite large. The average value of ℛ outside 2 kpc is 9.8 ± 0.6 ± 1.2 with a standard deviation of 4.5. An increase in the CO/13CO intensity ratio from disk to nucleus may imply that the conversion factor between CO intensity and H2 column density, X, is lower in galactic nuclei. In addition, variations in physical conditions, most notably the gas kinetic temperature, affect both ℛ and X. Abundance variations probably do not cause the gradient in ℛ, though we do not rule out a decrease in effective cloud column densities in galactic nuclei possibly caused by destructive starburst superwinds. A modest rise in temperature (less than a factor of 2 or 3) from outside a 2 kpc radius toward the nucleus can easily account for the observed gradient. These results support previous work implying that X is lower in the center of the Milky Way and probably most galactic nuclei. Therefore, calculating H2 masses using the standard Galactic X-factor, especially within the central few kiloparsecs of galaxies, overestimates the true mass by factors of a few. The standard X-factor still appears to be appropriate for galactic disks.