354 research outputs found
Energy consumption and capacity utilization of galvanizing furnaces
An explicit equation leading to a method for improving furnace efficiency is presented. This equation is dimensionless and can be applied to furnaces of any size and fuel type for the purposes of comparison. The implications for current furnace design are discussed. Currently the technique most commonly used to reduce energy consumption in galvanizing furnaces is to increase burner turndown. This is shown by the analysis presented here actually to worsen the thermal efficiency of the furnace, particularly at low levels of capacity utilization. Galvanizing furnaces are different to many furnaces used within industry, as a quantity of material (in this case zinc) is kept molten within the furnace at all times, even outside production periods. The dimensionless analysis can, however, be applied to furnaces with the same operational function as a galvanizing furnace, such as some furnaces utilized within the glass industry. © IMechE 2004
Dioxins do not only bind to AHR but also team up with EGFR at the cell-surface: a novel mode of action of toxicological relevance?
Dioxins and dioxin-like compounds (DLCs) are highly toxic organic pollutants whose production and use are prohibited by international law. Despite this, these biopersistent and lipophilic chemicals are prevalent in the environment and accumulate in the food chain, posing significant health risks to consumers even at low exposure levels. Acute dioxin intoxication can cause chloracne, while chronic exposure has been associated with a wide range of adverse health effects, including carcinogenicity, reproductive and developmental disorders, immunotoxicity, and endocrine disruption. In the mid-1970s, scientists identified a transcription factor known as the aryl hydrocarbon receptor (AHR), which becomes activated upon binding of dioxins. AHR orchestrates numerous adaptive and maladaptive stress responses and is believed to mediate most, if not all, of the toxic effects triggered by dioxins and DLCs. Recent studies have provided mounting evidence that dioxins and dioxin-like polychlorinated biphenyls can inhibit growth factor-induced activation of the epidermal growth factor receptor (EGFR) by directly binding to its extracellular domain. This interaction prevents the activation of EGFR by polypeptide growth factors and downstream signal transduction. In this article, we explain this newly identified mechanism of action for dioxins and DLCs in detail and discuss its potential toxicological relevance by using two examples, i.e. breast cancer development and placental toxicity. Finally, we briefly refer to other environmental chemicals of global concern that, based on first published data, may act via the same mode of action. See also the graphical abstract(Fig. 1)
Identification of the flotillin-1/2 heterocomplex as a target of autoantibodies in bona fide multiple sclerosis
Background: Autoantibodies, in particular those against aquaporin-4 and myelin-oligodendrocyte glycoprotein (MOG), aid as biomarkers in the differential diagnosis of demyelination. Here, we report on discovery of autoantibodies against flotillin in patients with multiple sclerosis (MS). Methods: The target antigen was identified by histo-immunoprecipitation using the patients’ sera and cryosections of rat or pig cerebellum combined with mass spectrometrical analysis. Correct identification was ascertained by indirect immunofluorescence and neutralization tests using the target antigens recombinantly expressed in HEK293 cells. Results: Serum and CSF of the index patient produced a fine-granular IgG indirect immunofluorescence staining of the hippocampal and cerebellar molecular layers. Flotillin-1 and flotillin-2 were identified as target autoantigens. They also reacted with recombinant human flotillin-1/2 co-expressed in HEK293 cells, but not with the individual flotillins in fixed- and live-cell assays. Moreover, neutralization using flotillin-1/2, but not the single flotillins, abolished the tissue reactivity of patient serum. Screening of 521 patients, for whom anti-aquaporin-4 testing was requested and negative, revealed 8 additional patients with anti-flotillin-1/2 autoantibodies. All eight were negative for anti-MOG. Six patients ex post fulfilled the revised McDonald criteria for MS. Vice versa, screening of 538 MS sera revealed anti-flotillin-1/2 autoantibodies in eight patients. The autoantibodies were not found in a cohort of 67 patients with other neural autoantibody-associated syndromes and in 444 healthy blood donors. Conclusions: Autoantibodies against the flotillin-1/2 heterocomplex, a peripheral membrane protein that is involved in axon outgrowth and regeneration of the optic nerve, are present in 1–2% of patients with bona fide MS
Current challenges of research on filamentous fungi in relation to human welfare and a sustainable bio-economy: a white paper.
The EUROFUNG network is a virtual centre of multidisciplinary expertise in the field of fungal biotechnology. The first academic-industry Think Tank was hosted by EUROFUNG to summarise the state of the art and future challenges in fungal biology and biotechnology in the coming decade. Currently, fungal cell factories are important for bulk manufacturing of organic acids, proteins, enzymes, secondary metabolites and active pharmaceutical ingredients in white and red biotechnology. In contrast, fungal pathogens of humans kill more people than malaria or tuberculosis. Fungi are significantly impacting on global food security, damaging global crop production, causing disease in domesticated animals, and spoiling an estimated 10 % of harvested crops. A number of challenges now need to be addressed to improve our strategies to control fungal pathogenicity and to optimise the use of fungi as sources for novel compounds and as cell factories for large scale manufacture of bio-based products. This white paper reports on the discussions of the Think Tank meeting and the suggestions made for moving fungal bio(techno)logy forward
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Plant-symbiotic fungi as chemical engineers: multi-genome analysis of the Clavicipitaceae reveals dynamics of alkaloid Loci
The fungal family Clavicipitaceae includes plant symbionts and parasites that produce several psychoactive and bioprotective alkaloids. The family includes grass symbionts in the epichloae clade (Epichloë and Neotyphodium species), which are extraordinarily diverse both in their host interactions and in their alkaloid profiles. Epichloae produce alkaloids of four distinct classes, all of which deter insects, and some—including the infamous ergot alkaloids—have potent effects on mammals. The exceptional chemotypic diversity of the epichloae may relate to their broad range of host interactions, whereby some are pathogenic and contagious, others are mutualistic and vertically transmitted (seed-borne), and still others vary in pathogenic or mutualistic behavior. We profiled the alkaloids and sequenced the genomes of 10 epichloae, three ergot fungi (Claviceps species), a morning-glory symbiont (Periglandula ipomoeae), and a bamboo pathogen (Aciculosporium take), and compared the gene clusters for four classes of alkaloids. Results indicated a strong tendency for alkaloid loci to have conserved cores that specify the skeleton structures and peripheral genes that determine chemical variations that are known to affect their pharmacological specificities. Generally, gene locations in cluster peripheries positioned them near to transposon-derived, AT-rich repeat blocks, which were probably involved in gene losses, duplications, and neofunctionalizations. The alkaloid loci in the epichloae had unusual structures riddled with large, complex, and dynamic repeat blocks. This feature was not reflective of overall differences in repeat contents in the genomes, nor was it characteristic of most other specialized metabolism loci. The organization and dynamics of alkaloid loci and abundant repeat blocks in the epichloae suggested that these fungi are under selection for alkaloid diversification. We suggest that such selection is related to the variable life histories of the epichloae, their protective roles as symbionts, and their associations with the highly speciose and ecologically diverse cool-season grasses
Modelling climate and societal resilience in the Eastern Mediterranean in the last Millennium
This article analyses high-quality hydroclimate proxy records and spatial reconstructions from the Central and Eastern Mediterranean and compares them with two Earth System Model simulations (CCSM4, MPI-ESM-P) for the Crusader period in the Levant (1095–1290 CE), the Mamluk regime in Transjordan (1260–1516 CE) and the Ottoman crisis and Celâlî Rebellion(1580–1610 CE). During the three time intervals, environmental and climatic stress tested the resilience of complex societies.We find that the multidecadal precipitation and drought variations in the Central and Eastern Mediterranean cannot be explained by external forcings (solar variations, tropical volcanism); rather they were driven by internal climate dynamics. Our research emphasises the challenges, opportunities and limitations of linking proxy records, palaeoreconstructions and model simulations to better understand how climate can affect human history
Muscle wasting as an independent predictor of survival in patients with chronic heart failure
Background:
Skeletal muscle wasting is an extremely common feature in patients with heart failure, affecting approximately 20% of ambulatory patients with even higher values during acute decompensation. Its occurrence is associated with reduced exercise capacity, muscle strength, and quality of life. We sought to investigate if the presence of muscle wasting carries prognostic information.
Methods:
Two hundred sixty‐eight ambulatory patients with heart failure (age 67.1 ± 10.9 years, New York Heart Association class 2.3 ± 0.6, left ventricular ejection fraction 39 ± 13.3%, and 21% female) were prospectively enrolled as part of the Studies Investigating Co‐morbidities Aggravating Heart Failure. Muscle wasting as assessed using dual‐energy X‐ray absorptiometry was present in 47 patients (17.5%).
Results
During a mean follow‐up of 67.2 ± 28.02 months, 95 patients (35.4%) died from any cause. After adjusting for age, New York Heart Association class, left ventricular ejection fraction, creatinine, N‐terminal pro‐B‐type natriuretic peptide, and iron deficiency, muscle wasting remained an independent predictor of death (hazard ratio 1.80, 95% confidence interval 1.01–3.19, P = 0.04). This effect was more pronounced in patients with heart failure with reduced than in heart failure with preserved ejection fraction.
Conclusions:
Muscle wasting is an independent predictor of death in ambulatory patients with heart failure. Clinical trials are needed to identify treatment approaches to this co‐morbidity
Expanding the Social Security Net in South Africa: Opportunities, Challenges and Constraints
Rapid increases in government expenditure on social security between 2000 and 2006 has further increased poor households’ reliance on welfare grants and has been important in the fight against poverty. Already there is evidence of a substitution taking place within the social budget: expenditure on education and health seems to have declined in favour of increased welfare transfer expenditure
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