Miracle-dz/UniFAR-FTUs huggingface dataset:
Sheep-associated Malignant Catarrhal Fever in Free-ranging Moose (Alces alces) in Saskatchewan, Canada

Malignant catarrhal fever (MCF) is a sporadic disease of artiodactyls caused by several viruses in the Gammaherpesvirinae. We report two cases of MCF in free-living moose (Alces alces) from Saskatchewan. One was a thin, dehydrated, adult male found recumbent in 2006. At necropsy, ulcers were found in the intestine, bladder, and corneas. Microscopically, there was lymphocytic vasculitis and perivasculitis in many organs with infrequent fibrinoid necrosis. Ovine herpes virus-2 (OHV-2) was identified by polymerase chain reaction. A segment of the herpesviral DNA polymerase gene was 99% identical to published OHV-2 sequences. During a retrospective search of earlier cases, a female moose with lymphoplasmacytic meningoencephalitis examined in 2003 was identified and OHV-2 was amplified from paraffin-embedded tissues from this animal. We believe this to be the first description of MCF in free-ranging moose in North America. Infection requires contact with infected sheep or goats, and MCF in moose may become more prevalent as moose distribution continues to expand into agricultural prairie.
HSP70-2 is required for desynapsis of synaptonemal complexes during meiotic prophase in juvenile and adult mouse spermatocytes.

Spermatogenic cells synthesize a unique 70-kDa heat shock protein (HSP70-2) during prophase of meiosis I, and targeted disruption of the Hsp70-2 gene has shown that this protein is required for spermatogenic cell differentiation in adult mice. HSP70-2 is associated with synaptonemal complexes formed between paired homologous chromosomes during meiotic prophase. The present study focuses on the nearly synchronous first wave of spermatogenesis in 12- to 28-day old juvenile mice to determine more precisely when HSP70-2 is required and what meiotic processes are affected by its absence. Spermatogenesis in homozygous mutant mice (Hsp70-2[-/-]) proceeded normally until day 15 when increasing numbers of pachytene spermatocytes became apoptotic and differentiation of cells beyond the pachytene stage began to falter. Synaptonemal complexes assembled in Hsp70-2(-/-) mice and spermatocytes developed through the final pachytene substage. However, synaptonemal complexes failed to desynapse and normal diplotene spermatocytes were not observed. Metaphase spermatocytes were not seen in tissue sections from testes of Hsp70-2(-/-) mice, and expression of mRNAs and antigens characteristic of late pachytene spermatocytes (e.g., cyclin A1) and development of spermatids did not occur. Thus, HSP70-2 is required for synaptonemal complex desynapsis, and its absence severely impairs the transition of spermatogenic cells through the late meiotic stages and results in apoptosis beginning with the first wave of germ cell development in juvenile mice.
Quantitative changes in the synaptic vesicle proteins synapsin I and p38 and the astrocyte-specific protein glial fibrillary acidic protein are associated with chemical-induced injury to the rat central nervous system

Measurements of neuron-specific and glia-specific proteins were used to characterize chemical-induced injury to the rat CNS. Trimethyltin (TMT), a neurotoxicant that preferentially damages neurons in limbic structures, was employed to produce consistent, time-dependent, dose- related, cell type-specific alterations in CNS morphology. Brain weights and histology were used to verify the cytopathological effects of TMT. Accompanying changes in 2 synaptic vesicle-associated proteins, synapsin I and p38, and the astrocyte-associated protein, glial fibrillary acidic protein (GFAP), were measured by radioimmunoassay (RIA). Immunohistochemistry of GFAP and incorporation of 3H-thymidine into GFAP-positive astrocytes also were used to characterize astrocytic responses to TMT-induced injury. Finally, quantitative 2-dimensional PAGE was employed to detect additional proteins affected by TMT. Acute administration of TMT caused large dose- and time-dependent decreases in synapsin I and p38 in hippocampus; the same proteins were largely unaffected in a nonlimbic structure, the frontal cortex. Twelve weeks after dosing, the concentrations of synapsin I and p38 and, to a lesser extent, the absolute amount of these proteins in hippocampus had returned to near control values, findings that are suggestive of reactive synaptogenesis. TMT caused large dose- and time-dependent increases in GFAP that were not confined to hippocampus. Twelve weeks after dosing, the amounts of GFAP in hippocampus and frontal cortex had returned to near control values, findings indicative of a transient astrocytic response to brain injury. Immunohistochemistry of GFAP revealed widespread astrocytic reactivity as a consequence of exposure to TMT, a response that resulted in part from the proliferation of astrocytes. Additional neurotypic proteins altered by TMT-induced injury included one of the neurofilament (NF) triplet proteins (p68) and a protein with the electrophoretic characteristics of neuron- specific enolase (NSE). The data indicate that measurements of neurotypic and gliotypic proteins may be used to characterize the temporal and regional patterns of neuronal and glial responses to injury.
Domain Architecture of a Calcium-Permeable AMPA Receptor in a Ligand-Free Conformation

Ligand-gated ion channels couple the free energy of agonist binding to the gating of selective transmembrane ion pores, permitting cells to regulate ion flux in response to external chemical stimuli. However, the stereochemical mechanisms responsible for this coupling remain obscure. In the case of the ionotropic glutamate receptors (iGluRs), the modular nature of receptor subunits has facilitated structural analysis of the N-terminal domain (NTD), and of multiple conformations of the ligand-binding domain (LBD). Recently, the crystallographic structure of an antagonist-bound form of the receptor was determined. However, disulfide trapping of this conformation blocks channel opening, suggesting that channel activation involves additional quaternary packing arrangements. To explore the conformational space available to iGluR channels, we report here a second, clearly distinct domain architecture of homotetrameric, calcium-permeable AMPA receptors, determined by single-particle electron microscopy of untagged and fluorescently tagged constructs in a ligand-free state. It reveals a novel packing of NTD dimers, and a separation of LBD dimers across a central vestibule. In this arrangement, which reconciles diverse functional observations, agonist-induced cleft closure across LBD dimers can be converted into a twisting motion that provides a basis for receptor activation.
Bisprasin, a Novel Ca 2 1 Releaser with Caffeine-Like Properties from a Marine Sponge, Dysidea spp., Acts on Ca 2 1 -Induced Ca 2 1 Release Channels of Skeletal Muscle Sarcoplasmic Reticulum 1

Bisprasin, a unique bromotyrosine derivative containing a di- sulfide linkage, was isolated from a marine sponge of Dysidea spp. This compound caused a concentration-dependent (from 10 to 30 m M) increase in the 45 Ca 2 1 release from the heavy fraction of skeletal muscle sarcoplasmic reticulum (HSR) of rabbit skeletal muscle in the same way as does caffeine. The 50% effective concentrations of bisprasin and caffeine were approximately 18 m M and 1.2 mM, respectively, indicating that the 45 Ca 2 1 -releasing activity of bisprasin was approximately 70 times more potent than that of caffeine in HSR. The bell-shaped profile of Ca 2 1 dependence for bisprasin was almost the same as that for caffeine. Typical blockers of Ca 2 1 -induced Ca 2 1 release channels, such as Mg 2 1 , procaine, and ruthenium red, inhibited markedly bisprasin- and caffeine-induced 45 Ca 2 1 release from HSR. This compound, like caffeine, significantly enhanced [ 3 H]ryanodine binding to HSR. Scatchard analysis of [ 3 H]ryanodine binding to HSR revealed that bisprasin and caffeine decreased the K D value without affecting the B max value, suggesting that both the drugs facilitate the opening of ryanodine receptor channels. The bisprasin- and caffeine-induced increases in [ 3 H]ryanodine binding were further enhanced by adenosine-5 9 -( b , g -methylene)triphosphate. These results suggest that the pharmacological properties of bisprasin are al- most similar to those of caffeine, except for its 70-fold higher potency. Here, we present the first report on the pharmacolog- ical properties of bisprasin, which, like caffeine, induces Ca 2 1 release from skeletal muscle SR mediated through the ryano- dine receptor.
Defining the Estimated Core Genome of Bacterial Populations Using a Bayesian Decision Model

The bacterial core genome is of intense interest and the volume of whole genome sequence data in the public domain available to investigate it has increased dramatically. The aim of our study was to develop a model to estimate the bacterial core genome from next-generation whole genome sequencing data and use this model to identify novel genes associated with important biological functions. Five bacterial datasets were analysed, comprising 2096 genomes in total. We developed a Bayesian decision model to estimate the number of core genes, calculated pairwise evolutionary distances (p-distances) based on nucleotide sequence diversity, and plotted the median p-distance for each core gene relative to its genome location. We designed visually-informative genome diagrams to depict areas of interest in genomes. Case studies demonstrated how the model could identify areas for further study, e.g. 25% of the core genes with higher sequence diversity in the Campylobacter jejuni and Neisseria meningitidis genomes encoded hypothetical proteins. The core gene with the highest p-distance value in C. jejuni was annotated in the reference genome as a putative hydrolase, but further work revealed that it shared sequence homology with beta-lactamase/metallo-beta-lactamases (enzymes that provide resistance to a range of broad-spectrum antibiotics) and thioredoxin reductase genes (which reduce oxidative stress and are essential for DNA replication) in other C. jejuni genomes. Our Bayesian model of estimating the core genome is principled, easy to use and can be applied to large genome datasets. This study also highlighted the lack of knowledge currently available for many core genes in bacterial genomes of significant global public health importance.
Network meta-analysis of the efficacy of first-line chemotherapy regimens in patients with advanced colorectal cancer

This network meta-analysis compared the short-term and long-term efficacies of first-line chemotherapy regimens in patients with advanced colorectal cancer (CRC). The 10 regimens included folinic acid + 5-fluorouracil + oxaliplatin (FOLFOX), folinic acid + 5-fluorouracil + irinotecan (FOLFIRI), folinic acid + 5-fluorouracil + gemcitabine (FFG), folinic acid + 5-fluorouracil + trimetrexate (FFT), folinic acid + 5-fluorouracil (FF), irinotecan + oxaliplatin (IROX), raltitrexed + oxaliplatin (TOMOX), folinic acid + tegafur-uracil (FTU), raltitrexed, and capecitabine. Electronic searches were performed in the Cochrane Library, PubMed and Embase databases from inception to June 2017. Network meta-analysis combined direct and indirect evidence to obtain odds ratios (ORs) and surface under the cumulative ranking curves (SUCRA) of different chemotherapy regimens for advanced CRC. Fourteen randomized controlled trails (RCTs) covering 4,383 patients with advanced CRC were included. The results revealed that FOLFOX, FOLFIRI, IROX, and TOMOX all showed higher overall response rates (ORRs) than FF or raltitrexed. Compared with raltitrexed, the aforementioned four regimens also had higher 1-year progression-free survival (PFS) rates. In addition, FOLFOX and FOLFIRI exhibited higher disease control rates (DCRs) and 1-year PFS rates than FF or raltitrexed. Cluster analysis revealed that FOLFOX, FOLFIRI, and TOMOX had better short-term and long-term efficacies. These findings suggest FOLFOX, FOLFIRI, and TOMOX are superior to other regimens for advanced CRC. These three regimens are therefore recommended for clinical treatment of advanced CRC.
Counting Low-Copy Number Proteins in a Single Cell

We have designed a microfluidic device in which we can manipulate, lyse, label, separate, and quantify the protein contents of a single cell using single-molecule fluorescence counting. Generic labeling of proteins is achieved through fluorescent-antibody binding. The use of cylindrical optics enables high-efficiency (≈60%) counting of molecules in micrometer-sized channels. We used this microfluidic device to quantify β2 adrenergic receptors expressed in insect cells (SF9). We also analyzed phycobiliprotein contents in individual cyanobacterial cells (Synechococcus sp. PCC 7942) and observed marked differences in the levels of specific complexes in cell populations that were grown under nitrogen-depleted conditions.
Why the Maternal Brain?

In the rat, the change from a virgin/nulliparous female to the maternal animal takes place at many levels. A subtle developmental wave washes over the female nervous system and transforms her from largely self‐centred to offspring‐directed, from personal care and protection to care of genetically‐related offspring, from indifference to ardour. Such change is preceded by substantial and apparently permanent neural alterations, the depth of which results in the maternal brain, and is the basis of the present review. The neuroplasticity of pregnancy, inherent to the female brain and, we believe, representative of the full expression of the female nervous system’s capacity, is a result of significant hormonal and other neurochemical actions. It results in the striking brain changes that are associated with, and necessary for, successful reproduction. We discuss some of these changes and their ramifications. Collectively, they represent the culmination of mammalian evolution and have led to the development of the social brain characteristic of higher orders of mammal, including the human. We also examine different facets of the maternal brain, beginning with a review of the genes involved in maternal behaviour, and in the subsequent ‘expression’ of the maternal brain. We next discuss olfaction and the manner in which this major sense draws from the rich sensory milieu of the mother to regulate and support maternal behaviour. Last, we discuss the ‘whys’ of maternal behaviour, a theoretical foray into the reasons for such substantial maternal brain alterations. We focus on the male’s potential role as the raison d’etre for the manifest alterations in his mate’s brain. In the end, it is clear that the female brain undergoes a significant reorganisation en route to motherhood, the results of which are deep and enduring.
Detecting, Representing and Querying Collusion in Online Rating Systems

Online rating systems are subject to malicious behaviors mainly by posting unfair rating scores. Users may try to individually or collaboratively promote or demote a product. Collaborating unfair rating 'collusion' is more damaging than individual unfair rating. Although collusion detection in general has been widely studied, identifying collusion groups in online rating systems is less studied and needs more investigation. In this paper, we study impact of collusion in online rating systems and asses their susceptibility to collusion attacks. The proposed model uses a frequent itemset mining algorithm to detect candidate collusion groups. Then, several indicators are used for identifying collusion groups and for estimating how damaging such colluding groups might be. Also, we propose an algorithm for finding possible collusive subgroup inside larger groups which are not identified as collusive. The model has been implemented and we present results of experimental evaluation of our methodology.
Characterization of Changes in Serum Anti-Glycan Antibodies in Crohn's Disease – a Longitudinal Analysis

Introduction Anti-glycan antibodies are a promising tool for differential diagnosis and disease stratification of patients with Crohn's disease (CD). We longitudinally assessed level and status changes of anti-glycan antibodies over time in individual CD patients as well as determinants of this phenomenon. Methods 859 serum samples derived from a cohort of 253 inflammatory bowel disease (IBD) patients (207 CD, 46 ulcerative colitis (UC)) were tested for the presence of anti-laminarin (Anti-L), anti-chitin (Anti-C), anti-chitobioside (ACCA), anti-laminaribioside (ALCA), anti-mannobioside (AMCA) and anti-Saccharomyces cerevisiae (gASCA) antibodies by ELISA. All patients had at least two and up to eleven serum samples taken during the disease course. Results Median follow-up time for CD was 17.4 months (Interquartile range (IQR) 8.0, 31.6 months) and for UC 10.9 months (IQR 4.9, 21.0 months). In a subgroup of CD subjects marked changes in the overall immune response (quartile sum score) and levels of individual markers were observed over time. The marker status (positive versus negative) remained widely stable. Neither clinical phenotype nor NOD2 genotype was associated with the observed fluctuations. In a longitudinal analysis neither changes in disease activity nor CD behavior led to alterations in the levels of the glycan markers. The ability of the panel to discriminate CD from UC or its association with CD phenotypes remained stable during follow-up. In the serum of UC patients neither significant level nor status changes were observed. Conclusions While the levels of anti-glycan antibodies fluctuate in a subgroup of CD patients the antibody status is widely stable over time.
Resveratrol and Endothelial Nitric Oxide

Nitric oxide (NO) derived from the endothelial NO synthase (eNOS) has antihypertensive, antithrombotic, anti-atherosclerotic and antiobesogenic properties. Resveratrol is a polyphenol phytoalexin with multiple cardiovascular and metabolic effects. Part of the beneficial effects of resveratrol are mediated by eNOS. Resveratrol stimulates NO production from eNOS by a number of mechanisms, including upregulation of eNOS expression, stimulation of eNOS enzymatic activity and reversal of eNOS uncoupling. In addition, by reducing oxidative stress, resveratrol prevents oxidative NO inactivation by superoxide thereby enhancing NO bioavailability. Molecular pathways underlying these effects of resveratrol involve SIRT1, AMPK, Nrf2 and estrogen receptors.
How power relations structure the evaluation process for HRD Programmes

Abstract Centring on the impact of power and politics embedded in the evaluation of training programmes, this study aimed to understand how organizational power relations affect the evaluation process for a training programme. A qualitative case study for the managerial leadership development programme of a Korean insurance company was designed. The HRD practitioners held control throughout the evaluation, and their dominant power was maintained and reproduced by other stakeholders' recognition of their expertise in training and development area. However, due to the structural relationship between the HRD unit and the corporate management, the HRD practitioners perceived themselves as marginalized. Unequal power relations were sustained in the evaluation mostly by stakeholders' self-regulation of their conduct in terms of norms, standards and expectations about their roles. This study found that despite the immense criticism of reaction measures, their continuing use in evaluation could be traced to their meaning as a political bargaining tool.
An Analysis of the Conceptions of Language in the Twentieth-Century's Philosophy of Language

All concepts, methods, and techniques of the philosophy of language arise from its conceptions of language. Conceptions of language have determined the character of the philosophy of language and the direction of its philosophical research. Various schools and currents within the philosophy of language differ from each other, mainly in the way they understand the referential character of the sign—that is, the relationship between the meaning of a word and its referential object (referent).
Occupational Stratification across the Life Course: Evidence from the Wisconsin Longitudinal Study

Sociologists frequently study changes across cohorts in the consequences of family background, gender, education, and cognitive ability for occupational outcomes. This study focuses, however, on how the consequences of these variables change within the course of individuals’ lives. To appropriately estimate changes across the life course in the determinants of occupational standing, corrections are made for measurement errors in variables, and data on siblings are used to account for all aspects (measured and unmeasured) of family background. The analyses use data from the Wisconsin Longitudinal Study, which provides multiple measures of siblings’ occupational standing at four points in their lives. Models of sibling resemblance show that the effects of family background on occupational standing operate entirely through their effects on education and cognitive ability. The effects of education decline across the life course, while the effects of ability remain small but persistent. In comparing men and women, substantial differences are found in career trajectories and in life course changes in occupational returns to schooling.
Deconstructing myth: low-carbon sustainability

Informed by a semiotics that directs attention to the context of the message, this paper contributes to work on the meanings of terms such as “low-carbon”, “green”, and “sustainability”. Interview-based evidence and printed material are used to assess the interest of hundreds of financial institutions in data on carbon emissions levels and environmental projects. The collection of such data is where for most interviewees its usefulness stopped. Such is typical of myth. By collecting carbon data, financial institutions can connote they are doing something about addressing the risks posed by global warming, without actually describing what it is they are doing.
Likelihood analysis of phylogenetic networks using directed graphical models.

A method for computing the likelihood of a set of sequences assuming a phylogenetic network as an evolutionary hypothesis is presented. The approach applies directed graphical models to sequence evolution on networks and is a natural generalization of earlier work by Felsenstein on evolutionary trees, including it as a special case. The likelihood computation involves several steps. First, the phylogenetic network is rooted to form a directed acyclic graph (DAG). Then, applying standard models for nucleotide/amino acid substitution, the DAG is converted into a Bayesian network from which the joint probability distribution involving all nodes of the network can be directly read. The joint probability is explicitly dependent on branch lengths and on recombination parameters (prior probability of a parent sequence). The likelihood of the data assuming no knowledge of hidden nodes is obtained by marginalization, i.e., by summing over all combinations of unknown states. As the number of terms increases exponentially with the number of hidden nodes, a Markov chain Monte Carlo procedure (Gibbs sampling) is used to accurately approximate the likelihood by summing over the most important states only. Investigating a human T-cell lymphotropic virus (HTLV) data set and optimizing both branch lengths and recombination parameters, we find that the likelihood of a corresponding phylogenetic network outperforms a set of competing evolutionary trees. In general, except for the case of a tree, the likelihood of a network will be dependent on the choice of the root, even if a reversible model of substitution is applied. Thus, the method also provides a way in which to root a phylogenetic network by choosing a node that produces a most likely network.