Miracle-dz/UniFAR-FTUs huggingface dataset:
C6 depletion reduces proteinuria in experimental nephropathy induced by a nonglomerular antigen.

The role of the complement membrane attack complex, C5b-9, in mediating glomerular injury has been well defined in models of membranous nephropathy induced by antibody to endogenous glomerular epithelial cell membrane antigens. The effect of selective C6 depletion (to prevent C5b-9 formation) on morphologic characteristics and proteinuria in a model of in situ subepithelial immune complex nephritis induced by an exogenous cationized antigen (human immunoglobulin G (IgG)) followed by rabbit antibody to human IgG was studied. Selective C6 depletion was achieved by repeated administration of a goat antibody to rat C6. Other groups were treated with cobra venom factor to induce generalized complement depletion and with sublethal irradiation to deplete circulating leukocytes. In C6-depleted rats, C6 levels were reduced to less than 3% of baseline throughout the 2 days of the study compared with over 100% in controls. At 4 h after disease induction, glomerular deposition of antigen and antibody were similar in C6D and control groups by immunofluorescence and by direct measurement of glomerular deposition of radiolabeled antigen and antibody (cationized 131I human IgG, 9.1 +/- 0.1 micrograms/38,000 glomeruli in C6D versus 9.8 +/- 0.9 in controls; P = was not significant; rabbit 125I-labeled anti-human IgG, 104 +/- 10 ng in C6D versus 80 +/- 9 ng in controls; P = was not significant). Circulating C3 levels and glomerular C3 deposition were also similar in C6D and control groups. (ABSTRACT TRUNCATED AT 250 WORDS)
Are Gamers Better Crossers? An Examination of Action Video Game Experience and Dual Task Effects in a Simulated Street Crossing Task

Objective: A high-fidelity street crossing simulator was used to test the hypothesis that experienced action video game players are less vulnerable than nongamers to dual task costs in complex tasks. Background: Previous research has shown that action video game players outperform nonplayers on many single task measures of perception and attention. It is unclear, however, whether action video game players outperform nonplayers in complex, divided attention tasks. Method: Experienced action video game players and nongamers completed a street crossing task in a high-fidelity simulator. Participants walked on a manual treadmill to cross the street. During some crossings, a cognitively demanding working memory task was added. Results: Dividing attention resulted in more collisions and increased decision making time. Of importance, these dual task costs were equivalent for the action video game players and the nongamers. Conclusion These results suggest that action video game players are equally susceptible to the costs of dividing attention in a complex task. Application: Perceptual and attentional benefits associated with action video game experience may not translate to performance benefits in complex, real-world tasks.
Five-year patient outcomes with risperidone long-acting injection or oral aripiprazole

Background: This study examined 5-year outcomes of patients prescribed risperidone long-acting injection (RLAI) or aripiprazole in a clinical setting, using treatment discontinuation as a measure of effectiveness. Method: Patients who received RLAI or aripiprazole in the 18 months following their respective UK launches were included. Two-year outcome data were previously reported for these cohorts; this study reported an additional 3 years of follow up for each group. Data were collected from pharmacy records and by retrospective case note review. Patients were classified as continuers or discontinuers at 5 years and reasons for treatment discontinuation noted. Results: The number of patients remaining on treatment at 2 years (and included in this study) was 28/84 and 27/92 for RLAI and aripiprazole respectively. Two patients treated with RLAI and three treated with aripiprazole were lost to follow up. Therefore, 5-year outcome data were available for 50 patients. Fifteen patients from each group were continuers at 5 years. Of these, four receiving RLAI and three receiving aripiprazole were coprescribed other antipsychotics at study endpoint. Reasons for discontinuation of RLAI and aripiprazole respectively were lack of effect (n = 4; n = 4), adverse effects (n = 3; n = 1), noncompliance or patient choice (n = 2; n = 4) and patient death (n = 2; n = 0). Conclusion: There was no significant difference between the proportions of patients continuing RLAI or aripiprazole for 5 years. Continuation rates were relatively low (18% and 16% of the original RLAI and aripiprazole cohorts respectively), whilst coprescription of other antipsychotics at endpoint was relatively common. Lack of effectiveness was the most common reason for discontinuation of both compounds. These findings suggested that clinical effectiveness was somewhat disappointing, although the long period of follow up and number of patients previously treated with clozapine in the original cohorts were confounding factors.
The Kingdom of Rheged: A Landscape Perspective

Abstract For over a century scholars have been wrestling with early Welsh poetry and associated texts in an attempt to shed light on the activities of North British kings resisting the expansion of the kingdoms of Bernicia and Northumbria. This paper first of all questions some of the historical reasoning about the kingdom of Rheged, especially its location and extent. Secondly, looking at the period from an archaeological perspective, it identifies potential heartlands on either side of the Solway. Although the location of Rheged cannot, and probably never will, be settled, it is suggested that it is unlikely to have straddled both sides of the Solway. Whichever heartland scholars may prefer, the natural advantages of the areas highlighted including the landscape, the resource potential and communications, would have provided a powerful incentive for the Northumbrians intent on expanding westwards.
Whole-Genome Sequencing Identifies STAT4 as a Putative Susceptibility Gene in Classic Kaposi Sarcoma.

BACKGROUND Classic Kaposi sarcoma (cKS) is an inflammatory tumor caused by human herpesvirus 8 (HHV-8) commonly observed in elderly men of Mediterranean origin. We studied a Finnish family of 5 affected individuals in 2 generations. Except for atypical mycobacterial infection of the index case, the affected individuals did not have notable histories of infection. METHODS We performed genome and exome sequencing and mapped shared chromosomal regions to identify genetic predisposition in the family. RESULTS We identified 12 protein-coding candidate variants that segregated in the 3 affected cousins from whom we had samples. The affected mother of the index case was an obligatory carrier. Among the 12 candidates was a rare heterozygous substitution rs141331848 (c.1337C>T, p.Thr446Ile) in the DNA-binding domain of STAT4. The variant was not present in 242 Finnish control genomes or 180 additional regional controls. Activated T-helper cells from the HHV-8-negative variant carriers showed reduced interferon γ production, compared with age and sex matched wild-type individuals. We screened STAT4 in additional 18 familial KS cases and the variant site from 56 sporadic KS cases but detected no pathogenic mutations. CONCLUSIONS Our data suggest that STAT4 is a potential cKS-predisposition gene, but further functional and genetic validation is needed.
Determinants of Outcome in the Treatment of Rotator Cuff Disease

One hundred thirty-six patients with impingement syndrome and rotator cuff disease who were treated nonoperatively from 1987 to 1991 were reviewed to identify findings at initial presentation that correlated with final outcome. Mean followup was 20 months (range, 6–41 months). All patients received initial conservative treatment. The results were analyzed in 2 groups. Group I consisted of the entire 136 patients with a minimum 6-month followup. Group II consisted of a subgroup of 68 patients with at least an 18-month followup. The overall results in Group I were 66% excellent and good and 34% fair and poor. For Group II, the overall results were 76% excellent and good and 24% fair and poor. For the Group II patients, a distribution of clinical findings at the 6-month followup demonstrated only 46% excellent and good results, indicating that the clinical result improves significantly as followup duration increased. Patient characteristics and prognostic factors that were associated with an unfavorable clinical outcome included a rotator cuff tear >1 cm2, a history of pretreatment clinical symptoms for >1-year duration, and significant functional impairment at initial presentation. Factors not associated with clinical outcome included patient age, occupation, gender, associated instability, dominance, chronicity of onset, active range of motion, or specific treatment modalities. Early operative intervention is recommended for patients with poor prognostic factors to avoid a protracted clinical course.
Voices from the Past: Sources of Seventeenth-Century Spoken French

Dans cet article nous consid? rons dans quelle mesure il nous est possible d'identifier des sources du fran? ais parl? au XVIIe si? cle. Les sources cit? es par Ernst (1980) les transcrip tions du fran? ais parl? authentique, les dialogues mod? les, le discours direct soit dans le th? tre soit dans les textes narratifs, les textes m? talinguistiques, la reconstruction compara tive sont ? valu? es, et d'autres sources ? ventuelles sont propos? es. Nous pouvons conclure qu'il est imprudent de compter sur une seule source; il faut plut? t chercher la convergence entre les sources de genre diff? rent, m? me si cette approche n'est pas sans probl? mes.
Evaluation of Leakage From Fume Hoods Using Tracer Gas, Tracer Nanoparticles and Nanopowder Handling Test Methodologies

The most commonly reported control used to minimize workplace exposures to nanomaterials is the chemical fume hood. Studies have shown, however, that significant releases of nanoparticles can occur when materials are handled inside fume hoods. This study evaluated the performance of a new commercially available nano fume hood using three different test protocols. Tracer gas, tracer nanoparticle, and nanopowder handling protocols were used to evaluate the hood. A static test procedure using tracer gas (sulfur hexafluoride) and nanoparticles as well as an active test using an operator handling nanoalumina were conducted. A commercially available particle generator was used to produce sodium chloride tracer nanoparticles. Containment effectiveness was evaluated by sampling both in the breathing zone (BZ) of a mannequin and operator as well as across the hood opening. These containment tests were conducted across a range of hood face velocities (60, 80, and 100 ft/min) and with the room ventilation system turned off and on. For the tracer gas and tracer nanoparticle tests, leakage was much more prominent on the left side of the hood (closest to the room supply air diffuser) although some leakage was noted on the right side and in the BZ sample locations. During the tracer gas and tracer nanoparticle tests, leakage was primarily noted when the room air conditioner was on for both the low and medium hood exhaust airflows. When the room air conditioner was turned off, the static tracer gas tests showed good containment across most test conditions. The tracer gas and nanoparticle test results were well correlated showing hood leakage under the same conditions and at the same sample locations. The impact of a room air conditioner was demonstrated with containment being adversely impacted during the use of room air ventilation. The tracer nanoparticle approach is a simple method requiring minimal setup and instrumentation. However, the method requires the reduction in background concentrations to allow for increased sensitivity.
The cariostatic mechanisms of fluoride.

UNLABELLED This article discusses the possible cariostatic mechanisms of the action of fluoride. In the past, fluoride inhibition of caries was ascribed to reduced solubility of enamel due to incorporation of fluoride (F-) into the enamel minerals. The present evidence from clinical and laboratory studies suggests that the caries-preventive mode of action of fluoride is mainly topical. There is convincing evidence that fluoride has a major effect on demineralisation and remineralisation of dental hard tissue. The source of this fluoride could either be fluorapatite (formed due to the incorporation of fluoride into enamel) or calcium fluoride (CaF2)-like precipitates, which are formed on the enamel and in the plaque after application of topical fluoride. Calcium fluoride deposits are protected from rapid dissolution by a phosphate -protein coating of salivary origin. At lower pH, the coating is lost and an increased dissolution rate of calcium fluoride occurs. The CaF2, therefore, act as an efficient source of free fluoride ions during the cariogenic challenge. The current evidence indicates that fluoride has a direct and indirect effect on bacterial cells, although the in vivo implications of this are still not clear. CONCLUSION A better understanding of the mechanisms of the action of fluoride is very important for caries prevention and control. The effectiveness of fluoride as a cariostatic agent depends on the availability of free fluoride in plaque during cariogenic challenge, i.e. during acid production. Thus, a constant supply of low levels of fluoride in biofilm/saliva/dental interference is considered the most beneficial in preventing dental caries.
A Subset of Tumor-Derived Mutant Forms of p53 Down-Regulate p63 and p73 through a Direct Interaction with the p53 Core Domain

ABSTRACT The p53 protein is related by sequence homology and function to the products of two other genes, p63 and p73, that each encode several isoforms. We and others have discovered previously that certain tumor-derived mutants of p53 can associate and inhibit transcriptional activation by the α and β isoforms of p73. In this study we have extended these observations to show that in transfected cells a number of mutant p53 proteins could bind and down-regulate several isoforms not only of p73 (p73α, -β, -γ, and -δ) but also of p63 (p63α and -γ; ΔNp63α and -γ). Moreover, a correlation existed between the efficiency of p53 binding and the inhibition of p63 or p73 function. We also found that wild-type p63 and p73 interact efficiently with each other when coexpressed in mammalian cells. The interaction between p53 mutants and p63 or p73 was confirmed in a physiological setting by examining tumor cell lines that endogenously express these proteins. We also demonstrated that purified p53 and p73 proteins interact directly and that the p53 core domain, but not the tetramerization domain, mediates this interaction. Using a monoclonal antibody (PAb240) that recognizes an epitope within the core domain of a subset of p53 mutants, we found a correlation between the ability of p53 proteins to be immunoprecipitated by this antibody and their ability to interact with p73 or p63 in vitro and in transfected cells. Based on these results and those of others, we propose that interactions between the members of the p53 family are likely to be widespread and may account in some cases for the ability of tumor-derived p53 mutants to promote tumorigenesis.
Vibrio cholerae VibF Is Required for Vibriobactin Synthesis and Is a Member of the Family of Nonribosomal Peptide Synthetases

ABSTRACT A 7.5-kbp fragment of chromosomal DNA downstream of theVibrio cholerae vibriobactin outer membrane receptor,viuA, and the vibriobactin utilization gene,viuB, was recovered from a Sau3A lambda library of O395 chromosomal DNA. By analogy with the genetic organization of the Escherichia coli enterobactin gene cluster, in which the enterobactin biosynthetic and transport genes lie adjacent to the enterobactin outer membrane receptor, fepA, and the utilization gene, fes, the cloned DNA was examined for the ability to restore siderophore synthesis to E. coli entmutants. Cross-feeding studies demonstrated that an E. coli entF mutant complemented with the cloned DNA regained the ability to synthesize enterobactin and to grow in low-iron medium. Sequence analysis of the cloned chromosomal DNA revealed an open reading frame downstream of viuB which encoded a deduced protein of greater than 2,158 amino acids, homologous to Yersinia sp. HMWP2, Vibrio anguillarum AngR, and E. coliEntF. A mutant with an in-frame deletion of this gene, namedvibF, was created with classical V. choleraestrain O395 by in vivo marker exchange. In cross-feeding studies, this mutant was unable to synthesize ferric vibriobactin but was able to utilize exogenous siderophore. Complementation of the mutant with a cloned vibF fragment restored vibriobactin synthesis to normal. The expression of the vibF promoter was found to be negatively regulated by iron at the transcriptional level, under the control of the V. cholerae fur gene. Expression ofvibF was not autoregulatory and neither affected nor was affected by the expression of irgA or viuA. The promoter of vibF was located by primer extension and was found to contain a dyad symmetric nucleotide sequence highly homologous to the E. coli Fur binding consensus sequence. A footprint of purified V. cholerae Fur on the vibFpromoter, overlapping the Fur binding consensus sequence, was observed using DNase I footprinting. The protein product of vibF is homologous to the multifunctional nonribosomal protein synthetases and is necessary for the biosynthesis of vibriobactin.
Design of Triple-Frequency Microstrip-Fed Monopole Antenna Using Defected Ground Structure

A novel triple-frequency microstrip-fed planar monopole antenna for multiband operation is proposed and investigated. Defected ground structure (DGS) is used in this antenna, which has a rectangular patch with dual inverted L-shaped strips and is fed by a cross-shaped stripline, for achieving additional resonances and bandwidth enhancements. The designed antenna has a small overall size of 20 × 30 mm2, and operates over the frequency ranges, 2.14-2.52 GHz, 2.82-3.74 GHz, and 5.15-6.02 GHz suitable for WLAN 2.4/5.2/5.8 GHz and WiMAX 3.5/5.5 GHz applications. There is good agreement between the measured and simulated results. Experimental results show that the antenna gives monopole-like radiation patterns and good antenna gains over the operating bands. In addition, effects of both the length of the protrudent strips and the dimensions of the DGS for this design on the electromagnetic performance are examined and discussed in detail.
Ubiquity and quantitative significance of detoxification catabolism of chlorophyll associated with protistan herbivory

Chlorophylls are essential components of the photosynthetic apparati that sustain all of the life forms that ultimately depend on solar energy. However, a drawback of the extraordinary photosensitizing efficiency of certain chlorophyll species is their ability to generate harmful singlet oxygen. Recent studies have clarified the catabolic processes involved in the detoxification of chlorophylls in land plants, but little is understood about these strategies in aquatic ecosystem. Here, we report that a variety of heterotrophic protists accumulate the chlorophyll a catabolite 132,173-cyclopheophorbide a enol (cPPB-aE) after their ingestion of algae. This chlorophyll derivative is nonfluorescent in solution, and its inability to generate singlet oxygen in vitro qualifies it as a detoxified catabolite of chlorophyll a. Using a modified analytical method, we show that cPPB-aE is ubiquitous in aquatic environments, and it is often the major chlorophyll a derivative. Our findings suggest that cPPB-aE metabolism is one of the most important, widely distributed processes in aquatic ecosystems. Therefore, the herbivorous protists that convert chlorophyll a to cPPB-aE are suggested to play more significant roles in the modern oceanic carbon flux than was previously recognized, critically linking microscopic primary producers to the macroscopic food web and carbon sequestration in the ocean.
Long-term comparative immunogenicity of protein conjugate and free polysaccharide pneumococcal vaccines in chronic obstructive pulmonary disease.

BACKGROUND Although the 23-valent pneumococcal polysaccharide vaccine (PPSV23) protects against invasive disease in young healthy persons, randomized controlled trials in chronic obstructive pulmonary disease (COPD) have demonstrated no benefit in the intention-to-treat population. We previously reported that the 7-valent diphtheria-conjugated pneumococcal polysaccharide vaccine (PCV7) is safe and induced greater serotype-specific immunoglobulin G (IgG) and functional antibody than did PPSV23 1 month after vaccination. We hypothesized that these advantages would persist at 1 and 2 years. METHODS One hundred eighty-one patients with moderate to severe COPD were randomized to receive PPSV23 (n = 90) or PCV7 (1.0 mL; n = 91). We measured IgG by enzyme-linked immunosorbent assay and assessed functional antibody activity by a standardized opsonophagocytosis assay, reported as a killing index (OPK). We determined differences in IgG and OPK between vaccine groups at 1 and 2 years. RESULTS Relative to PPSV23, PCV7 induced greater OPK at both 1 and 2 years for 6 of 7 serotypes (not 19F). This response was statistically greater for 5 of 7 serotypes at 1 year and 4 of 7 at 2 years. Comparable differences in IgG were observed but were less often statistically significant. Despite meeting Centers for Disease Control and Prevention criteria for PPSV23 administration, almost 50% of individuals had never been vaccinated. No differences in the frequency of acute exacerbations, pneumonia, or hospitalization were observed. CONCLUSIONS PCV7 induces a greater functional antibody response than PPSV23 in patients with COPD that persists for 2 years after vaccination. This superior functional response supports testing of conjugate vaccination in studies examining clinical end points. CLINICAL TRIALS REGISTRATION NCT00457977.
Towards realisation of evolvable runtime variability in internet-based service systems via dynamical software update

Today’s Internet-based service systems tend to run in open environments and try to satisfy varying requirements. In the context, the changes of requirements and environments can emerge at any point of their life cycle, and their runtime variability is supposed to be evolvable to deal with the changes. In other words, the number, type or attribute of variability elements (variation points and their associated variants) in the systems is regarded to be changeable, especially at runtime. How to realise evolvable runtime variability in software systems is a challenge in the community of software engineering. Software architecture is supposed to support updating software without interrupting service if runtime variability is to be changed. Besides, the relevant mechanisms have to be provided to achieve dynamic update. Thus, we propose a dynamically reconfigurable reference architecture to construct the systems with evolvable software variability. The resultant system established using our approach consists of variability units and their containers. Variability units embody the variability elements that can be changed through local relay, i.e., starting a new version of variability unit to take place of older ones. Containers are mainly used to carry out the dynamic updating for variability units and realise the functionality invocation among different variability units. They can also be added, removed or replaced without shutting down the entire system. We analyse the requirements and scenarios of evolvable runtime variability in the case of Personal Data Resource Network, and further show the effectiveness and applicability of our approach by constructing the system using our class library and solving the issues proposed in the case.