Miracle-dz/UniFAR-FTUs huggingface dataset:
Anaplasma marginale Superinfection Attributable to Pathogen Strains with Distinct Genomic Backgrounds

ABSTRACT Strain superinfection occurs when a second pathogen strain infects a host already infected with a primary strain. The selective pressures that drive strain divergence, which underlies superinfection, and allow penetration of a new strain into a host population are critical knowledge gaps relevant to shifts in infectious disease epidemiology. In regions of endemicity with a high prevalence of infection, broad population immunity develops against Anaplasma marginale, a highly antigenically variant rickettsial pathogen, and creates strong selective pressure for emergence of and superinfection with strains that differ in their Msp2 variant repertoires. The strains may emerge either by msp2 locus duplication and allelic divergence on an existing genomic background or by introduction of a strain with a different msp2 allelic repertoire on a distinct genomic background. To answer this question, we developed a multilocus typing assay based on high-throughput sequencing of non-msp2 target loci to distinguish among strains with different genomic backgrounds. The technical error level was statistically defined based on the percentage of perfect sequence matches of clones of each target locus and validated using experimental single strains and strain pairs. Testing of A. marginale-positive samples from tropical regions where A. marginale infection is endemic identified individual infections that contained unique alleles for all five targeted loci. The data revealed a highly significant difference in the number of strains per animal in the tropical regions compared to infections in temperate regions and strongly supported the hypothesis that transmission of genomically distinct A. marginale strains predominates in high-prevalence areas of endemicity.
Ecological assessment of the marine ecosystems of Barbuda, West Indies: Using rapid scientific assessment to inform ocean zoning and fisheries management

To inform a community-based ocean zoning initiative, we conducted an intensive ecological assessment of the marine ecosystems of Barbuda, West Indies. We conducted 116 fish and 108 benthic surveys around the island, and measured the abundance and size structure of lobsters and conch at 52 and 35 sites, respectively. We found that both coral cover and fish biomass were similar to or lower than levels observed across the greater Caribbean; live coral cover and abundance of fishery target species, such as large snappers and groupers, was generally low. However, Barbuda lacks many of the high-relief forereef areas where similar work has been conducted in other Caribbean locations. The distribution of lobsters was patchy, making it difficult to quantify density at the island scale. However, the maximum size of lobsters was generally larger than in other locations in the Caribbean and similar to the maximum size reported 40 years ago. While the lobster population has clearly been heavily exploited, our data suggest that it is not as overexploited as in much of the rest of the Caribbean. Surveys of Barbuda’s Codrington Lagoon revealed many juvenile lobsters, but none of legal size (95 mm carapace length), suggesting that the lagoon functions primarily as nursery habitat. Conch abundance and size on Barbuda were similar to that of other Caribbean islands. Our data suggest that many of the regional threats observed on other Caribbean islands are present on Barbuda, but some resources—particularly lobster and conch—may be less overexploited than on other Caribbean islands. Local management has the potential to provide sustainability for at least some of the island’s marine resources. We show that a rapid, thorough ecological assessment can reveal clear conservation opportunities and facilitate rapid conservation action by providing the foundation for a community-driven policymaking process at the island scale.
Formulation study of topically applied lotion: in vitro and in vivo evaluation.

INTRODUCTION This article presents the development and evaluation of a new topical formulation of diclofenac diethylamine (DDA) as a locally applied analgesic lotion. METHODS To this end, the lotion formulations were formulated with equal volume of varying concentrations (1%, 2%, 3%, 4%; v/v) of permeation enhancers, namely propylene glycol (PG) and turpentine oil (TO). These lotions were subjected to physical studies (pH, viscosity, spreadability, homogeneity, and accelerated stability), in vitro permeation, in vivo animal studies and sensatory perception testing. In vitro permeation of DDA from lotion formulations was evaluated across polydimethylsiloxane membrane and rabbit skin using Franz cells. RESULTS It was found that PG and TO content influenced the permeation of DDA across model membranes with the lotion containing 4% v/v PG and TO content showed maximum permeation enhancement of DDA. The flux values for L4 were 1.20±0.02 μg. cm(-2). min(-1) and 0.67 ± 0.02 μg. cm(-2). min(-1) for polydimethylsiloxane and rabbit skin, respectively. Flux values were significantly different (p < 0.05) from that of the control. The flux enhancement ratio of DDA from L4 was 31.6-fold and 4.8-fold for polydimethylsiloxane and rabbit skin, respectively. In the in vivo animal testing, lotion with 4% v/v enhancer content showed maximum anti-inflammatory and analgesic effect without inducing any irritation. Sensatory perception tests involving healthy volunteers rated the formulations between 3 and 4 (values ranging between -4 to +4, indicating a range of very bad to excellent, respectively). CONCLUSION It was concluded that the DDA lotion containing 4% v/v PG and TO exhibit the best performance overall and that this specific formulation should be the basis for further clinical investigations.
Semantic Role Labeling of Chinese Using Transductive SVM and Semantic Heuristics

Semantic Role Labeling (SRL) as a Shallow Semantic Parsing causes more and more attention recently. The shortage of manually tagged data is one of main obstacles to supervised learning, which is even serious in SRL. Transductive SVM (TSVM) is a novel semi-supervised learning method special to small mount of tagged data. In this paper, we introduce an application of TSVM in Chinese SRL. To improve the performance of TSVM, some heuristics have been designed from the semantic perspective. The experiment results on Chinese Propbank showed that TSVM outperforms SVM in small tagged data, and after using heuristics, it performs further better.
Nasal polyposis: an inflammatory condition requiring effective anti-inflammatory treatment

Purpose of reviewRecent literature in chronic rhinosinusitis with nasal polyps (CRSwNP) has focussed on inflammatory mechanisms underlying the disease. Endotyping the histopathological features of the disease, rather than simple clinical phenotypes, reflects a change in our understanding of the disease and approach to management. This is paralleled by renewed evidence for the need for wide postsurgical access and topical anti-inflammatory therapy. Recent findingsRecent research into patterns of dysfunction in innate immunity suggests a crucial role of respiratory epithelium in mediating the inflammatory response. Elevated interleukins, IL-25 and IL-33, from sinus mucosa in CRSwNP and their interaction via innate lymphoid cells may represent the link between the host-environment interface and T-helper 2 dominated inflammation that characterizes CRSwNP. While thorough immunological profiling of CRSwNP is not routinely available, classification of CRS as eosinophilic (ECRS) or noneosinophilic is practical and correlates with disease severity and prognosis. The practice and utility of endoscopic sinus surgery to create a single neosinus for topical corticosteroid delivery is a logical conclusion founded on the inflammatory basis of CRSwNP/ECRS. SummaryThere is mounting evidence for CRSwNP as a predominantly inflammatory disease. Even simple histopathological classification on the basis of degrees of tissue eosinophilia reflects the underlying pathogenic mechanisms with diagnostic and prognostic implications. Optimal treatment involves topical anti-inflammatory therapy delivered locally via a wide, postsurgical corridor.
Predictors of Outcome for Orofacial Pain in the General Population: a Four-year Follow-up Study

Orofacial pain is often persistent, but it is not clear why it lasts in some patients but not in others. We aimed to describe the natural course of orofacial pain in a general population sample over a four-year period and to identify factors that would predict the persistence of pain. A cross-sectional population-based survey was conducted in the United Kingdom, involving 2504 participants (participation rate 74%), of whom 646 (26%) reported orofacial pain. Overall, 424 (79% adjusted participation rate) of these individuals participated at the four-year follow-up, of whom 229 (54%) reported orofacial pain and 195 (46%) did not report such pain. Persistent orofacial pain was associated with females, older age, psychological distress, widespread body pain, and taking medication for orofacial pain at baseline. These findings may have implications for the identification and treatment of patients with orofacial pain.
ERK-Dependent T Cell Receptor Threshold Calibration in Rheumatoid Arthritis1

Immune responses to citrullinated neoantigens and clinical efficacy of costimulation blockade indicate a general defect in maintaining T cell tolerance in rheumatoid arthritis (RA). To examine whether TCR threshold calibration contributes to disease pathogenesis, signaling in RA T cells was quantified. RA patients had a selective increase in ERK phosphorylation compared with demographically matched controls due to a mechanism distal of Ras activation. Increased ERK responses included naive and memory CD4 and CD8 T cells and did not correlate with disease activity. The augmented ERK activity delayed SHP-1 recruitment to the TCR synapse and sustained TCR-induced Zap70 and NF-κB signaling, facilitating responses to suboptimal stimulation. Increased responsiveness of the ERK pathway was also a characteristic finding in the SKG mouse model of RA where it preceded clinical symptoms. Treatment with subtherapeutic doses of a MEK-1/2 inhibitor delayed arthritis onset and reduced severity, suggesting that increased ERK phosphorylation predisposes for autoimmunity and can be targeted to prevent disease.
Slope estimation in structural line‐segment heteroscedastic measurement error models

This paper extends the line‐segment parametrization of the structural measurement error (ME) model to situations in which the error variance on both variables is not constant over all observations. Under these conditions, we develop a method‐of‐moments estimate of the slope, and derive its asymptotic variance. We further derive an accurate estimator of the variability of the slope estimate based on sample data in a rather general setting. We perform simulations that validate our results and demonstrate that our estimates are more precise than estimates under a different model when the ME variance is not small. Finally, we illustrate our estimation approach using real data involving heteroscedastic ME, and compare its performance with that of earlier models. Copyright © 2010 John Wiley & Sons, Ltd.
Measurement and Bio-dynamic Model Development of Seated Human Subjects Exposed to Low Frequency Vibration Environment

In this study, the effect of posture, vibration magnitude and frequency on seat-to-head (STH) and back support-to-head (BTH) transfer functions has been studied under vertical sinusoidal vibration. Twelve healthy male subjects participated in experimental work to measure vertical vibration transmitted to the occupants’ heads in three representative postures (erect, vertical backrest and forward lean on table) under three magnitudes of vibration (0.4, 0.8 and 1.2 m/s2 r.m.s.) in frequency range 1 to 20 Hz. From collected data sets, the effects of vibration magnitude, vibration frequency and postures on STH and BTH transmissibility and phase were measured over the prescribed frequency range. The result suggested that inclusion of all possible variables in optimal design of vehicle seat, suspension and comfort analysis would improve the design and analysis. The comparison of experimental and model response reveals that both models matched with mean experimental data sets most closely and the models provide t.
Cell surface expression of an endoplasmic reticulum resident heat shock protein gp96 triggers MyD88-dependent systemic autoimmune diseases

Heat shock proteins have been implicated as endogenous activators for dendritic cells (DCs). Without tissue distress or death, these intracellular molecules are inaccessible to surface receptor(s) on DCs, possibly to avoid uncontrolled DC activation and breakdown of immunologic tolerance. We herein addressed this hypothesis in transgenic mice by enforcing cell surface expression of gp96, a ubiquitous heat shock protein of the endoplasmic reticulum. Although a pan-specific promoter is used for transgene expression, neither the expression level nor the tissue distribution of the endogenous gp96 was altered by this maneuver. However, cell surface gp96 induced significant DC activations and spontaneous lupus-like autoimmune diseases, even though the development/functions of lymphocytic compartments were unaltered. Using a bone marrow chimera approach, we further demonstrated that both DC activation and autoimmunity elicited by cell surface gp96 are dependent on the downstream adaptor protein MyD88 for signaling by Toll/IL-1 receptor family. Our study not only established the proinflammatory property of cell surface gp96 in vivo, but also suggested a chronic stimulation of DCs by gp96 as a pathway to initiate spontaneous autoimmune diseases.
Discrete Fuzzy Particle Swarm Optimization for Solving Traveling Salesman Problem

Discrete fuzzy PSO (D-FPSO) algorithm based on Continues fuzzy PSO is proposed in this paper. According to this new algorithm, charisma is defined to be a fuzzy variable, and more than one particle in each neighborhood is allowed to influence others to a degree that depends on its charisma. Shift-neighborhood and mutation is employed to improve convergence speed and avoid to becoming trapped in the local optima. D-FPSO is evaluated on the TSP problem, comparing performance to other methods based on PSO
Matrix metalloproteinase (MMP) induction and inhibition at different doses of recombinant tissue plasminogen activator following experimental stroke

Summary Although recombinant tissue plasminogen activator (rt-PA) is successfully used for thrombolysis in human stroke, it may increase the risk of haemorrhagic complications. It was shown that the matrix metalloproteinase (MMP) system is critically involved in basal lamina degradation after middle cerebral artery occlusion and reperfusion following rt-PA administration. We describe the effects of different doses of rt-PA (saline, 0.9, 9, or 18 mg rt-PA/kg body weight) on the MMPs, their specific inhibitors (TIMPs), and also their inducer protein EMMPRIN following experimental cerebral ischemia (3 hours [h], 24 h reperfusion, suture model) in rats. The amount of MMP-2 and -9 was measured by gelatine zymography, TIMP-1 and -2 by reverse gelatine zymography, and the content of EMMPRIN and the basal lamina component collagen type IV by Western blotting. The amount of both MMPs steadily rose with increasing doses of rt- PA (p<0.05). In contrast, their endogenous inhibitors TIMPs decreased (p<0.001). A balance between the proteases and their inhibitors was achieved at the low dose of 0.9 mg/kg rt-PA in the rats, which significantly coincided with the demonstrated protection of collagen type IV degradation at this dose. The inducer protein EMMPRIN increased in parallel to its substrate MMP-2. Exogenous rt-PA leads to an increase of the MMP-inducing system by EMMPRIN, and a rise of the degrading MMPs follows. However, at low to moderate doses of rt-PA the microvascular basal lamina was protected, probably due to inhibition of MMP-2 and MMP-9 by the upregulation of their inhibitors. This strongly supports use of the lowest effective dosage of rt-PA available.
Remember the Source: Dissociating Frontal and Parietal Contributions to Episodic Memory

Event-related fMRI studies reveal that episodic memory retrieval modulates lateral and medial parietal cortices, dorsal middle frontal gyrus (MFG), and anterior PFC. These regions respond more for recognized old than correctly rejected new words, suggesting a neural correlate of retrieval success. Despite significant efforts examining retrieval success regions, their role in retrieval remains largely unknown. Here we asked the question, to what degree are the regions performing memory-specific operations? And if so, are they all equally sensitive to successful retrieval, or are other factors such as error detection also implicated? We investigated this question by testing whether activity in retrieval success regions was associated with task-specific contingencies (i.e., perceived targetness) or mnemonic relevance (e.g., retrieval of source context). To do this, we used a source memory task that required discrimination between remembered targets and remembered nontargets. For a given region, the modulation of neural activity by a situational factor such as target status would suggest a more domain-general role; similarly, modulations of activity linked to error detection would suggest a role in monitoring and control rather than the accumulation of evidence from memory per se. We found that parietal retrieval success regions exhibited greater activity for items receiving correct than incorrect source responses, whereas frontal retrieval success regions were most active on error trials, suggesting that posterior regions signal successful retrieval whereas frontal regions monitor retrieval outcome. In addition, perceived targetness failed to modulate fMRI activity in any retrieval success region, suggesting that these regions are retrieval specific. We discuss the different functions that these regions may support and propose an accumulator model that captures the different pattern of responses seen in frontal and parietal retrieval success regions.
Information Frictions and Real Exchange Rate Dynamics

Real exchange rates are highly volatile and persistent. I provide a novel structural explanation for these facts using a model with dispersed information among firms. When producers face strategic complementarities in price-setting, uncertainty about competitors' beliefs results in sluggish price adjustment that can generate large and long-lived real exchange rate movements. I estimate the model using data from the US and Euro Area, and show that it successfully explains the unconditional volatility and persistence of the real exchange rate. The model also accounts for the persistent and hump-shaped real exchange rate behavior conditional on nominal disturbances documented by a structural VAR. About 50% of this persistence is due to the inertial dynamics of higher-order beliefs.
New applications of pHluorin—measuring intracellular pH of prototrophic yeasts and determining changes in the buffering capacity of strains with affected potassium homeostasis

pHluorin is a pH‐sensitive variant of green fluorescent protein for measuring intracellular pH (pHin) in living cells. We constructed a new pHluorin plasmid with the dominant selection marker KanMX. This plasmid allows pH measurements in cells without auxotrophic mutations and/or grown in chemically indefinite media. We observed differing values of pHin for three prototrophic wild‐types. The new construct was also used to determine the pHin in strains differing in the activity of the plasma membrane Pma1 H+‐ATPase and the influence of glucose on pHin. We describe in detail pHluorin measurements performed in a microplate reader, which require much less hands‐on time and much lower cell culture volumes compared to standard cuvettes measurements. We also utilized pHluorin in a new method of measuring the buffering capacity of yeast cell cytosol in vivo, shown to be ca. 52 mM/pH for wild‐type yeast and moderately decreased in mutants with affected potassium transport. Copyright © 2010 John Wiley & Sons, Ltd.
Memory Bias for Threat in Generalized Anxiety Disorder: The Potential Importance of Stimulus Relevance

Information processing models propose that anxious individuals are characterized by memory biases for mood‐congruent threat information. However, evidence for memory biases in generalized anxiety disorder (GAD) has been mixed at best. Given the heterogeneity of concerns in GAD, previous use of nomothetic stimulus sets may have precluded detection of memory biases. Therefore, in order to guarantee the relevance of the stimuli used, in the current study individuals with GAD each individually selected words that were of personal relevance to them. Using these idiographically selected words with 23 individuals with DSM‐IV GAD and 23 non‐anxious controls (NACs), results showed an implicit memory bias for threat words in individuals with GAD compared with NACs. Furthermore, there was additional evidence that individuals with GAD may also be characterized by explicit memory bias for threat words. The magnitude of group differences for explicit recall of threat words was similar to those previously observed in panic disorder. Limitations and future directions are discussed.
The Roles of Compensatory Evolution and Constraint in Aminoacyl tRNA Synthetase Evolution

Mitochondrial protein translation requires interactions between transfer RNAs encoded by the mitochondrial genome (mt-tRNAs) and mitochondrial aminoacyl tRNA synthetase proteins (mt-aaRS) encoded by the nuclear genome. It has been argued that animal mt-tRNAs have higher deleterious substitution rates relative to their nuclear-encoded counterparts, the cytoplasmic tRNAs (cyt-tRNAs). This dynamic predicts elevated rates of compensatory evolution of mt-aaRS that interact with mt-tRNAs, relative to aaRS that interact with cyt-tRNAs (cyt-aaRS). We find that mt-aaRS do evolve at significantly higher rates (exemplified by higher dN and dN/dS) relative to cyt-aaRS, across mammals, birds, and Drosophila. While this pattern supports a model of compensatory evolution, the level at which a gene is expressed is a more general predictor of protein evolutionary rate. We find that gene expression level explains 10–56% of the variance in aaRS dN/dS, and that cyt-aaRS are more highly expressed in addition to having lower dN/dS values relative to mt-aaRS, consistent with more highly expressed genes being more evolutionarily constrained. Furthermore, we find no evidence of positive selection acting on either class of aaRS protein, as would be expected under a model of compensatory evolution. Nevertheless, the signature of faster mt-aaRS evolution persists in mammalian, but not bird or Drosophila, lineages after controlling for gene expression, suggesting some additional effect of compensatory evolution for mammalian mt-aaRS. We conclude that gene expression is the strongest factor governing differential amino acid substitution rates in proteins interacting with mitochondrial versus cytoplasmic factors, with important differences in mt-aaRS molecular evolution among taxonomic groups.