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Particulate matter (PM) air pollution poses a major global health risk, but the role of iron (Fe) is not clearly defined because chemistry at the particle-cell interface is often not considered. Detailed spectromicroscopy characterizations of PM2.5 samples from the San Joaquin Valley, CA identified major Fe-bearing components and estimated their relative proportions. Iron in ambient PM2.5 was present in spatially and temporally variable mixtures, mostly as Fe(III) oxides and phyllosilicates, but with significant fractions of metallic iron (Fe(0)), Fe(II,III) oxide, and Fe(III) bonded to organic carbon. Fe(0) was present as aggregated, nm-sized particles that comprised up to ∼30% of the Fe spectral fraction. Mixtures reflect anthropogenic and geogenic particles subjected to environmental weathering, but reduced Fe in PM originates from anthropogenic sources, likely as abrasion products. Possible mechanistic pathways involving Fe(0) particles and mixtures of Fe(II) and Fe(III) surface species may generate hydrogen peroxide and oxygen-centered radical species (hydroxyl, hydroperoxyl, or superoxide) in Fenton-type reactions. From a health perspective, PM mixtures with reduced and oxidized Fe will have a disproportionate effect in cellular response after inhalation because of their tendency to shuttle electrons and produce oxidants and electrophiles that induce inflammation and oxidative stress.

BACKGROUND: The pathophysiology of COVID-19 includes immune-mediated hyperinflammation, which could potentially lead to respiratory failure and death. Granulocyte-macrophage colony-stimulating factor (GM-CSF) is among cytokines that contribute to the inflammatory processes. Lenzilumab, a GM-CSF neutralising monoclonal antibody, was investigated in the LIVE-AIR trial to assess its efficacy and safety in treating COVID-19 beyond available treatments. METHODS: In LIVE-AIR, a phase 3, randomised, double-blind, placebo-controlled trial, hospitalised adult patients with COVID-19 pneumonia not requiring invasive mechanical ventilation were recruited from 29 sites in the USA and Brazil and were randomly assigned (1:1) to receive three intravenous doses of lenzilumab (600 mg per dose) or placebo delivered 8 h apart. All patients received standard supportive care, including the use of remdesivir and corticosteroids. Patients were stratified at randomisation by age and disease severity. The primary endpoint was survival without invasive mechanical ventilation to day 28 in the modified intention-to-treat population (mITT), comprising all randomised participants who received at least one dose of study drug under the documented supervision of the principal investigator or sub-investigator. Adverse events were assessed in all patients who received at least one dose of study drug. This trial is registered with ClinicalTrials.gov, NCT04351152, and is completed. FINDINGS: Patients were enrolled from May 5, 2020, until Jan 27, 2021. 528 patients were screened, of whom 520 were randomly assigned and included in the intention-to-treat population. 479 of these patients (n=236, lenzilumab; n=243, placebo) were included in the mITT analysis for the primary outcome. Baseline demographics were similar between groups. 311 (65%) participants were males, mean age was 61 (SD 14) years at baseline, and median C-reactive protein concentration was 79 (IQR 41-137) mg/L. Steroids were administered to 449 (94%) patients and remdesivir to 347 (72%) patients; 331 (69%) patients received both treatments. Survival without invasive mechanical ventilation to day 28 was achieved in 198 (84%; 95% CI 79-89) participants in the lenzilumab group and in 190 (78%; 72-83) patients in the placebo group, and the likelihood of survival was greater with lenzilumab than placebo (hazard ratio 1·54; 95% CI 1·02-2·32; p=0·040). 68 (27%) of 255 patients in the lenzilumab group and 84 (33%) of 257 patients in the placebo group experienced at least one adverse event that was at least grade 3 in severity based on CTCAE criteria. The most common treatment-emergent adverse events of grade 3 or higher were related to respiratory disorders (26%) and cardiac disorders (6%) and none led to death. INTERPRETATION: Lenzilumab significantly improved survival without invasive mechanical ventilation in hospitalised patients with COVID-19, with a safety profile similar to that of placebo. The added value of lenzilumab beyond other immunomodulators used to treat COVID-19 alongside steroids remains unknown. FUNDING: Humanigen.

Circuit breakers for residential branch circuits must trip at or below 135% of rated current. A breaker that fails that requirement is defective. Samples of two brands, purchased from retail sources, are tested for that basic calibration. Both brands were tested 4 years ago. Previous samples of one brand were 50% defective, and new samples manufactured in 2021 are 28% defective. The second brand, previously defect-free, is again defect-free. The test results, past and present, imply that some manufacturers are calibrating breakers to trip too close to the allowable upper current limit, and are checking calibration by testing at higher current. The standard calibration test at 200% of rated current is shown to be incapable of indicating whether or not a breaker will trip properly, as required by the applicable standard, at 135% of rated current. A third brand tested came on the market recently. Its thermal-magnetic breakers trip correctly, but the brand's hydraulic-magnetic breakers are erratic, with 38% of the samples malfunctioning. The malfunctions are attributed to thermal distortion that causes mechanical binding of the triggering mechanism. Some breaker brands with a high defect rate have been in the distribution chain for many years and are permanently installed in homes. The increased risk of fire and injury for the occupants of these dwellings is significant. The long-standing history of this problem and the fire safety consequences are discussed.

Using serial-section transmission electron microscopy and three-dimensional (3D) electron tomography, we characterized membrane dynamics that accompany the construction of a nuclear exchange junction between mating cells in the ciliate Tetrahymena thermophila. Our methods revealed a number of previously unknown features. (i) Membrane fusion is initiated by the extension of hundreds of 50-nm-diameter protrusions from the plasma membrane. These protrusions extend from both mating cells across the intercellular space to fuse with membrane of the mating partner. (ii) During this process, small membrane-bound vesicles or tubules are shed from the plasma membrane and into the extracellular space within the junction. The resultant vesicle-filled pockets within the extracellular space are referred to as junction lumens. (iii) As junction lumens fill with extracellular microvesicles and swell, the plasma membrane limiting these swellings undergoes another deformation, pinching off vesicle-filled vacuoles into the cytoplasm (reclamation). (iv) These structures (resembling multivesicular bodies) seem to associate with autophagosomes abundant near the exchange junction. We propose a model characterizing the membrane-remodeling events that establish cytoplasmic continuity between mating Tetrahymena cells. We also discuss the possible role of nonvesicular lipid transport in conditioning the exchange junction lipid environment. Finally, we raise the possibility of an intercellular signaling mechanism involving microvesicle shedding and uptake.

The experimental results are presented for minimum trip current as a function of temperature for residential circuit breakers. These are often installed in enclosures that are exposed to seasonal temperature extremes. The trip current of these thermally actuated breakers is inversely related to temperature. The relationship is shown to be linear and it varies as much as 2:1 between brands. The trip current at extremely high and low temperatures can be estimated. At low outside ambient temperature the worst case 15 A breakers will not trip at 25 A, which would be the current load of two 1500 W portable heaters plugged into the same 15 A circuit. The diminished overcurrent protection at low temperature may be a factor that contributes to the elevated incidence of residential electrical fires during winter months.

AbstractBackgroundWe present a comprehensive transcriptome analysis of the fungus Ascosphaera apis, an economically important pathogen of the Western honey bee (Apis mellifera) that causes chalkbrood disease. Our goals were to further annotate the A. apis reference genome and to identify genes that are candidates for being differentially expressed during host infection versus axenic culture.ResultsWe compared A. apis transcriptome sequence from mycelia grown on liquid or solid media with that dissected from host-infected tissue. 454 pyrosequencing provided 252 Mb of filtered sequence reads from both culture types that were assembled into 10,087 contigs. Transcript contigs, protein sequences from multiple fungal species, and ab initio gene predictions were included as evidence sources in the Maker gene prediction pipeline, resulting in 6,992 consensus gene models. A phylogeny based on 12 of these protein-coding loci further supported the taxonomic placement of Ascosphaera as sister to the core Onygenales. Several common protein domains were less abundant in A. apis compared with related ascomycete genomes, particularly cytochrome p450 and protein kinase domains. A novel gene family was identified that has expanded in some ascomycete lineages, but not others. We manually annotated genes with homologs in other fungal genomes that have known relevance to fungal virulence and life history. Functional categories of interest included genes involved in mating-type specification, intracellular signal transduction, and stress response. Computational and manual annotations have been made publicly available on the Bee Pests and Pathogens website.ConclusionsThis comprehensive transcriptome analysis substantially enhances our understanding of the A. apis genome and its expression during infection of honey bee larvae. It also provides resources for future molecular studies of chalkbrood disease and ultimately improved disease management.

Test results presented in this paper demonstrate that some brands of residential molded case circuit breakers do not operate properly within the limits specified by the applicable standard. The samples tested are both used, from homes, and new, purchased at retail sources. The minimum trip current is determined for each breaker. The test procedure encompasses the basic overload trip requirements of the applicable standard. Breakers that do not open the circuit at or below 135% of rated current fail to meet the requirements of the standard. Test results vary substantially from brand to brand. The best brands are essentially failure free. The failure rate of the worst-case brands is in the order of 50% for both used breakers from homes and new breakers recently purchased. Some samples, primarily multi-pole breakers, do not open the circuit at any level of applied current. Failure of a circuit breaker in a home to operate properly when required poses an increased risk of fire and injury.

Disneyland is work disguised as play; school disguised as vacation. While Walt Disney's curriculum deploys across all of its products, it literally engulfs the approximately 50 million "guests" who visit the Disney Parks each year. Drawing on Sarah Ahmed's phenomenological reading of orientation in Queer phenomenology, this article investigates the ways in which Disney's didacticism is made material through practices and procedures designed to orient the park's visitors, to ensure that those visitors always know where they are and who they are, as a means of educating "good" citizens. The argument focuses not on Disneyland's narrative curriculum but on its corporeal one: visitors are enticed to make affective investments, to construct or reconstruct their identities to comply with the Disney version of the ideal American worker and consumer, as the park attempts to reorient those who resist those roles. (Contains 21 notes.)

Pollinators, including honey bees, are responsible for the successful reproduction of more than 87% of flowering plant species: they are thus vital to ecosystem health and agricultural services world-wide. To investigate honey bee exposure to pesticides, 168 pollen samples and 142 wax comb samples were collected from colonies within six stationary apiaries in six U.S. states. These samples were analyzed for evidence of pesticides. Samples were taken bi-weekly when each colony was active. Each apiary included thirty colonies, of which five randomly chosen colonies in each apiary were sampled for pollen. The pollen samples were separately pooled by apiary. There were a total of 714 detections in the collected pollen and 1008 detections in collected wax. A total of 91 different compounds were detected: of these, 79 different pesticides and metabolites were observed in the pollen and 56 were observed in the wax. In all years, insecticides were detected more frequently than were fungicides or herbicides: one third of the detected pesticides were found only in pollen. The mean (standard deviation (SD)) number of detections per pooled pollen sample varied by location from 1.1 (1.1) to 8.7 (2.1). Ten different modes of action were found across all four years and nine additional modes of action occurred in only one year. If synergy in toxicological response is a function of simultaneous occurrence of multiple distinct modes of action, then a high frequency of potential synergies was found in pollen and wax-comb samples. Because only pooled pollen samples were obtained from each apiary, and these from only five colonies per apiary per year, more data are needed to adequately evaluate the differences in pesticide exposure risk to honey bees among colonies in the same apiary and by year and location.

Chronic bee paralysis virus (CBPV) is an important viral disease of adult bees which induces significant losses in honey bee colonies. Despite comprehensive research, only limited data is available from experimental infection for this virus. In the present study winter worker bees were experimentally infected in three different experiments. Bees were first inoculated per os (p/o) or per cuticle (p/c) with CBPV field strain M92/2010 in order to evaluate the virus replication in individual bees. In addition, potential synergistic effects of co-infection with CBPV and Nosema ceranae (N. ceranae) on bees were investigated. In total 558 individual bees were inoculated in small cages and data were analyzed using quantitative real time RT-PCR (RT-qPCR). Our results revealed successful replication of CBPV after p/o inoculation, while it was less effective when bees were inoculated p/c. Dead bees harbored about 1,000 times higher copy numbers of the virus than live bees. Co-infection of workers with CBPV and N. ceranae using either method of virus inoculation (p/c or p/o) showed increased replication ability for CBPV. In the third experiment the effect of inoculation on bee mortality was evaluated. The highest level of bee mortality was observed in a group of bees inoculated with CBPV p/o, followed by a group of workers simultaneously inoculated with CBPV and N. ceranae p/o, followed by the group inoculated with CBPV p/c and the group with only N. ceranae p/o. The experimental infection with CBPV showed important differences after p/o or p/c inoculation in winter bees, while simultaneous infection with CBPV and N. ceranae suggesting a synergistic effect after inoculation.

We investigated the effect of the parasitic mite Varroa destructor on the immunological and nutritional condition of honey bees, Apis mellifera, from the perspective of the individual bee and the colony. Pupae, newly-emerged adults and foraging adults were sampled from honey bee colonies at one site in S. Texas, USA. Varroa‑infested bees displayed elevated titer of Deformed Wing Virus (DWV), suggestive of depressed capacity to limit viral replication. Expression of genes coding three anti-microbial peptides (defensin1, abaecin, hymenoptaecin) was either not significantly different between Varroa-infested and uninfested bees or was significantly elevated in Varroa-infested bees, varying with sampling date and bee developmental age. The effect of Varroa on nutritional indices of the bees was complex, with protein, triglyceride, glycogen and sugar levels strongly influenced by life-stage of the bee and individual colony. Protein content was depressed and free amino acid content elevated in Varroa-infested pupae, suggesting that protein synthesis, and consequently growth, may be limited in these insects. No simple relationship between the values of nutritional and immune-related indices was observed, and colony-scale effects were indicated by the reduced weight of pupae in colonies with high Varroa abundance, irrespective of whether the individual pupa bore Varroa.

Taking Euroscepticism that mainly concentrates on the tension between European integration and the preservation of cultural diversity and national identity as a point of departure, this contribution serves as a normative observation of the Lisbon Treaties' competences and procedures in relation to the statement that the EU will respect cultural diversity and national identity. The question is whether the Lisbon Treaties are giving in to Euroscepticism by respecting and protecting diversity or whether the statements are only a window-dressing formality which, in reality, is not effectuated by the Union. When one looks at some Union developments and initiatives over the last few years, the EU's eventual ideal of becoming a more centralised political entity becomes clear. If, when looking at the new provisions in the Lisbon Treaties, this ideal is taken into account, the Treaties seem to reflect this progressive approach. Overall, it seems that 'Lisbon' has indeed considered the Eurosceptic arguments concerning a lack of democratic control and the tension concerning diversity and national identity. Nonetheless, the general signal expressed by the innovations seems to be that progressive integration by increased effectiveness is more important than the satisfaction of the Member States' wishes with regard to respect for cultural diversity and national identity. It may well be that this effectiveness results in a counter-effect: an intensification of Euroscepticism that may negatively reflect on the Union's progressive integration.

The special issue of IMPACT ON INSTRUCTIONAL IMPROVEMENT focuses on career education and presents an editorial and six articles in that area. The issue's theme editorial, Differing Views from Differing Perspectives, is by Laurence Aronstein. The articles included are: Infusing Career Education Concepts in the Curriculum, Albert J. Pautler, Jr.; Career Education--Interlude of Vocationalism or Emerging Curriculum Cluster?, Gordon Cawelti; Career Education in New York State, Robert S. Seckendorf; Career Education--Focal Point for Change, Marilyn F. Macchia; School-Industry Cooperative Career Education: A District Model, Donald M. Clark; and Career Education--Where Have I Heard This Song Before?, Diane Gess. A final article by Sally Evans is Using Teacher Evaluation Instruments Effectively. (NH)

Describes a multifaceted administrator leadership workshop that relies on case studies, role playing, and peer coaching exercises to enhance leadership skills. Administrators work collaboratively with staff members to analyze problems, prioritize needs, make decisions, and facilitate these three processes by using a repertoire of group dynamic skills. (MLH)

Describes documents developed for school business officials' self-assessment of seven major skill sets in "Professional Standards," published by the Association of School Business Officials in 2001. Documents are available from Professional Development section of Association's Web site at www.asbointl.org. (PKP)

A Bedford, Massachusetts, middle school lived through a series of critical incidents while moving into site-based management. Flaps developed over minute-taking responsibilities in faculty meetings and a student exchange arrangement with an inner-city middle school. A "pyramiding" process to close the communication gap helped maintain mutual trust. (MLH)

Abstract Background We present a comprehensive transcriptome analysis of the fungus Ascosphaera apis, an economically important pathogen of the Western honey bee (Apis mellifera) that causes chalkbrood disease. Our goals were to further annotate the A. apis reference genome and to identify genes that are candidates for being differentially expressed during host infection versus axenic culture. Results We compared A. apis transcriptome sequence from mycelia grown on liquid or solid media with that dissected from host-infected tissue. 454 pyrosequencing provided 252 Mb of filtered sequence reads from both culture types that were assembled into 10,087 contigs. Transcript contigs, protein sequences from multiple fungal species, and ab initio gene predictions were included as evidence sources in the Maker gene prediction pipeline, resulting in 6,992 consensus gene models. A phylogeny based on 12 of these protein-coding loci further supported the taxonomic placement of Ascosphaera as sister to the core Onygenales. Several common protein domains were less abundant in A. apis compared with related ascomycete genomes, particularly cytochrome p450 and protein kinase domains. A novel gene family was identified that has expanded in some ascomycete lineages, but not others. We manually annotated genes with homologs in other fungal genomes that have known relevance to fungal virulence and life history. Functional categories of interest included genes involved in mating-type specification, intracellular signal transduction, and stress response. Computational and manual annotations have been made publicly available on the Bee Pests and Pathogens website. Conclusions This comprehensive transcriptome analysis substantially enhances our understanding of the A. apis genome and its expression during infection of honey bee larvae. It also provides resources for future molecular studies of chalkbrood disease and ultimately improved disease management.

Abstract Background Diseases and other stress factors working synergistically weaken honey bee health and may play a major role in the losses of bee populations in recent years. Among a large number of bee diseases, chalkbrood has been on the rise. We present here the experimental identification of honey bee genes that are differentially expressed in response to infection of honey bee larvae with the chalkbrood fungus, Ascosphaera apis. Results We used cDNA-AFLP ®Technology to profile transcripts in infected and uninfected bee larvae. From 64 primer combinations, over 7,400 transcriptionally-derived fragments were obtained A total of 98 reproducible polymorphic cDNA-AFLP fragments were excised and sequenced, followed by quantitative real-time RT-PCR (qRT-PCR) analysis of these and additional samples. We have identified a number of differentially-regulated transcripts that are implicated in general mechanisms of stress adaptation, including energy metabolism and protein transport. One of the most interesting differentially-regulated transcripts is for a chitinase-like enzyme that may be linked to anti-fungal activities in the honey bee larvae, similarly to gut and fat-body specific chitinases found in mosquitoes and the red flour beetle. Surprisingly, we did not find many components of the well-characterized NF-κB intracellular signaling pathways to be differentially-regulated using the cDNA-AFLP approach. Therefore, utilizing qRT-PCR, we probed some of the immune related genes to determine whether the lack of up-regulation of their transcripts in our analysis can be attributed to lack of immune activation or to limitations of the cDNA-AFLP approach. Conclusions Using a combination of cDNA-AFLP and qRT-PCR analyses, we were able to determine several key transcriptional events that constitute the overall effort in the honey bee larvae to fight natural fungal infection. Honey bee transcripts identified in this study are involved in critical functions related to transcriptional regulation, apoptotic degradation of ubiquitinated proteins, nutritional regulation, and RNA processing. We found that immune regulation of the anti-fungal responses in honey bee involves highly coordinated activation of both NF-κB signaling pathways, leading to production of anti-microbial peptides. Significantly, activation of immune responses in the infected bee larvae was associated with down-regulation of major storage proteins, leading to depletion of nutritional resources.

The Adventures of Sir Galahad premiered as America's atomic narrative shifted from global cooperation to nuclear superiority. This Arthurian Western marked the beginning of Hollywood's Cold War engagement with the Arthurian legend, participating in the nation's nuclear discussion as it offered its audience a therapeutic narrative to ameliorate their atomic anxiety. (SA). [ABSTRACT FROM AUTHOR]

Ernest Cline's Ready Player One (2011) is a Grail tale for the Twitter-PS4-Wii generation masquerading as a postmodern techno-bildungsroman. [ABSTRACT FROM AUTHOR]

William Byron Forbush founded The Queens of Avalon in 1894 as a parallel organization to his Knights of the Round Table, to construct courtly ladies worthy of his chivalric knights. This essay examines the group's interpretation of Arthurian legend, founding principles, rituals and material culture in the context of Forbush's own anxieties about 'modern' girls and larger early-twentieth-century discussions of the 'girl problem.' For Forbush, the Queens of Avalon was the perfect 'antidote' to this problem as it returned girls to an idealized medieval past to teach them to perform their 'role in modern chivalry': inspiring and refining knights. [ABSTRACT FROM AUTHOR]