Obtaining Boiler Fuel Gas to Reduce Air Pollution: The Policy of the Federal Power Commission

Receptors interacting with the constant domain of immunoglobulins (Igs) have a number of important functions in vertebrates. They facilitate phagocytosis by opsonization, are key components in antibody-dependent cellular cytotoxicity as well as activating cells to release granules. In mammals, four major types of classical Fc receptors (FcRs) for IgG have been identified, one high-affinity receptor for IgE, one for both IgM and IgA, one for IgM and one for IgA. All of these receptors are related in structure and all of them, except the IgA receptor, are found in primates on chromosome 1, indicating that they originate from a common ancestor by successive gene duplications. The number of Ig isotypes has increased gradually during vertebrate evolution and this increase has likely been accompanied by a similar increase in isotype-specific receptors. To test this hypothesis we have performed a detailed bioinformatics analysis of a panel of vertebrate genomes. The first components to appear are the poly-Ig receptors (PIGRs), receptors similar to the classic FcRs in mammals, so called FcRL receptors, and the FcR gamma chain. These molecules are not found in cartilagous fish and may first appear within bony fishes, indicating a major step in Fc receptor evolution at the appearance of bony fish. In contrast, the receptor for IgA is only found in placental mammals, indicating a relatively late appearance. The IgM and IgA/M receptors are first observed in the monotremes, exemplified by the platypus, indicating an appearance during early mammalian evolution. Clearly identifiable classical receptors for IgG and IgE are found only in marsupials and placental mammals, but closely related receptors are found in the platypus, indicating a second major step in Fc receptor evolution during early mammalian evolution, involving the appearance of classical IgG and IgE receptors from FcRL molecules and IgM and IgA/M receptors from PIGR

A Healthy and Ecologically Balanced Environment: An Argument for a Third Generation Right

Chymotrypsin-like serine proteases are found in high abundance in mast cell granules. By site-directed mutatgenesis, we have previously shown that basic amino acids in positions 143 and 192 (Arg and Lys respectively) of the human mast cell chymase are responsible for an acidic amino acid residue preference in the P2' position of substrates. In order to study the influence of these two residues in determining the specificity of chymase inhibitors, we have synthesized five different potent inhibitors of the human chymase. The inhibitory effects of these compounds were tested against the wild-type enzyme, against two single mutants Arg143Gln and Lys192Met and against a double mutant, Arg143Gln+Lys192Met. We observed a markedly reduced activity of all five inhibitors with the double mutant, indicating that these two basic residues are involved in conferring the specificity of these inhibitors. The single mutants showed an intermediate phenotype, with the strongest effect on the inhibitor by the mutation in Lys192. The Lys192 and the double mutations also affected the rate of cleavage of angiotensin I but did not seem to affect the specificity in the cleavage of the Tyr(4)-Ile(5) bond. A more detailed knowledge about which amino acids that confer the specificity of an enzyme can prove to be of major importance for development of highly specific inhibitors for the human chymase and other medically important enzymes

Mast Cell and Basophil Granule Proteases-In Vivo Targets and Function

Proteases are stored in very large amounts within abundant cytoplasmic granules of mast cells (MCs), and in lower amounts in basophils. These proteases are stored in their active form in complex with negatively charged proteoglycans, such as heparin and chondroitin sulfate, ready for rapid release upon MC and basophil activation. The absolute majority of these proteases belong to the large family of chymotrypsin related serine proteases. Three such enzymes are found in human MCs, a chymotryptic enzyme, the chymase, a tryptic enzyme, the tryptase and cathepsin G. Cathepsin G has in primates both chymase and tryptase activity. MCs also express a MC specific exopeptidase, carboxypeptidase A3 (CPA3). The targets and thereby the functions of these enzymes have for many years been the major question of the field. However, the fact that some of these enzymes have a relatively broad specificity has made it difficult to obtain reliable information about the biologically most important targets for these enzymes. Under optimal conditions they may cleave a relatively large number of potential targets. Three of these enzymes, the chymase, the tryptase and CPA3, have been shown to inactivate several venoms from snakes, scorpions, bees and Gila monster. The chymase has also been shown to cleave several connective tissue components and thereby to be an important player in connective tissue homeostasis. This enzyme can also generate angiotensin II (Ang II) by cleavage of Ang I and have thereby a role in blood pressure regulation. It also display anticoagulant activity by cleaving fibrinogen and thrombin. A regulatory function on excessive T(H)2 immunity has also been observed for both the chymase and the tryptase by cleavage of a highly selective set of cytokines and chemokines. The chymase also appear to have a protective role against ectoparasites such as ticks, mosquitos and leeches by the cleavage of their anticoagulant proteins. We here review the data that has accumulated concerning the potential in vivo functions of these enzymes and we discuss how this information sheds new light on the role of MCs and basophils in health and disease

Two granzyme A/K homologs in Zebra mbuna have different specificities, one classical tryptase and one with chymase activity

Granzymes A and K are two highly homologous serine proteases expressed by mammalian cytotoxic T cells (CTLs) and natural killer (NK) cells. The locus encoding these two proteases is the first of the hematopoietic serine protease loci to appear during vertebrate evolution. This locus is found in all jawed vertebrates including the cartilaginous fishes. Granzyme A is the most abundant of the different granzymes expressed by CTLs and NK cells and its potential function has been studied extensively for many years. However, no clear conclusions concerning its primary role in the immune defense has been obtained. In all mammals, there are only one copy each of granzyme A and K, whereas additional copies are found in both cartilaginous and ray finned fishes. In cichlids two of these copies seem to encode new members of the granzyme A/K family. These two new members appear to have changed primary specificity and to be pure chymases based on the amino acids in their active site substrate binding pockets. Interestingly, one of these gene copies is located in the middle of the granzyme A/K locus, while the other copy is present in another locus, the met-ase locus. We here present a detailed characterization of the extended cleavage specificity of one of these non-classical granzymes, a Zebra mbuna granzyme positioned in the granzyme A/K locus. This enzyme, named granzyme A2, showed a high preference for tyrosine in the P1 position of substrates, thereby being a strict chymase. We have also characterized one of the classical granzyme A/Ks of the Zebra mbuna, granzyme A1, which is a tryptase with preference for arginine in the P1 position of substrates. Based on their extended specificities, the two granzymes showed major similarities, but also some differences in preferred amino acids in positions surrounding the cleavable amino acid. Fish lack one of the hematopoietic serine protease loci of mammals, the chymase locus, where one of the major mast cell enzymes is located. An interesting question is now if cichlids have by compensatory mechanisms generated a mast cell chymase from another locus, and if similar chymotryptic enzymes have appeared also in other fish species

Immigrant students in Nordic educational policy documents

Peer reviewe

Selectivity of the First Two Glycerol Dehydrogenation Steps Determined Using Scaling Relationships

Glycerol is a byproduct of biodiesel production and an abundant feedstock that can be used for the synthesis of high-value chemicals. There are many approaches for glycerol valorization, but, due to the complicated reaction mechanism, controlling which products are produced is challenging. Here, we describe glycerol\u27s chemical selectivity for different metallic catalysts using descriptors for carbon (mainly *C, *CH2OH) and oxygen (mainly *O, CH3O*). The quality of these descriptors and the weighted combinations thereof are validated based on their fit, via linear regression, to the binding energies of all reaction intermediates generated in the first two glycerol dehydrogenation steps on a number of close-packed Ru, Co, Rh, Ir, Ni, Pd, Pt, Cu, Ag, and Au surfaces. We show that *CH2OH is a better descriptor than *C for the studied carbon-bound intermediates, which is attributed to the observation that the adjacent *OH group interacts with the surface. This leads to a negative oxygen dependence, which can be generalized to similar alcohol-derived adsorbates. Furthermore, we show that CH3O* is a better oxygen descriptor than *0 for the studied intermediates. This is mainly attributed to the difference between the single and double bonds, as we show that *OH is closer to the accuracy of CH3O*. Multilinear regression with different combinations of *C, *O, and *OH is comparable in accuracy to that of *CH2OH and CH3O*. Scaling relationships are used to determine the selectivity map for glycerol dehydrogenation. The results show that the first dehydrogenation is selective toward two different intermediates (one bonded via the secondary carbon and the other via the secondary oxygen) depending on the relative bond strength of the carbon and oxygen descriptors. The second dehydrogenation step results in five intermediates, again depending primarily on the relative bond strength of carbon and oxygen to the surface. The selectivity maps can be used together with kinetic considerations and experimental data to find catalyst candidates for glycerol dehydrogenation

The Human Monocyte-A Circulating Sensor of Infection and a Potent and Rapid Inducer of Inflammation

Monocytes were previously thought to be the precursors of all tissue macrophages but have recently been found to represent a unique population of cells, distinct from the majority of tissue macrophages. Monocytes and intestinal macrophages seem now to be the only monocyte/macrophage populations that originate primarily from adult bone marrow. To obtain a better view of the biological function of monocytes and how they differ from tissue macrophages, we have performed a quantitative analysis of its transcriptome in vivo and after in vitro stimulation with E. coli LPS. The monocytes rapidly responded to LPS by producing extremely high amounts of mRNA for the classical inflammatory cytokines, IL-1 alpha, IL-1 beta, IL-6 and TNF-alpha, but almost undetectable amounts of other cytokines. IL-6 was upregulated 58,000 times, from almost undetectable levels at baseline to become one of the major transcripts already after a few hours of cultivation. The cells also showed very strong upregulation of a number of chemokines, primarily IL-8, Ccl2, Ccl3, Ccl3L3, Ccl20, Cxcl2, Cxcl3 and Cxcl4. IL-8 became the most highly expressed transcript in the monocytes already after four hours of in vitro culture in the presence of LPS. A high baseline level of MHC class II chains and marked upregulation of super oxide dismutase (SOD2), complement factor B, complement factor C3 and coagulation factor 3 (F3; tissue factor) at four hours of in vitro culture were also observed. This indicates a rapid protective response to high production of oxygen radicals, to increase complement activation and possibly also be an inducer of local coagulation. Overall, these findings give strong support for monocytes acting primarily as potent mobile sensors of infection and rapid activators of a strong inflammatory response

Quantitative Transcriptome Analysis of Purified Equine Mast Cells Identifies a Dominant Mucosal Mast Cell Population with Possible Inflammatory Functions in Airways of Asthmatic Horses

Asthma is a chronic inflammatory airway disease and a serious health problem in horses as well as in humans. In humans and mice, mast cells (MCs) are known to be directly involved in asthma pathology and subtypes of MCs accumulate in different lung and airway compartments. The role and phenotype of MCs in equine asthma has not been well documented, although an accumulation of MCs in bronchoalveolar lavage fluid (BALF) is frequently seen. To characterize the phenotype of airway MCs in equine asthma we here developed a protocol, based on MACS Tyto sorting, resulting in the isolation of 92.9% pure MCs from horse BALF. We then used quantitative transcriptome analyses to determine the gene expression profile of the purified MCs compared with total BALF cells. We found that the MCs exhibited a protease profile typical for the classical mucosal MC subtype, as demonstrated by the expression of tryptase (TPSB2) alone, with no expression of chymase (CMA1) or carboxypeptidase A3 (CPA3). Moreover, the expression of genes involved in antigen presentation and complement activation strongly implicates an inflammatory role for these MCs. This study provides a first insight into the phenotype of equine MCs in BALF and their potential role in the airways of asthmatic horses

NFC based provisioning of instructional videos to assist with instrumental activities of daily living

The file attached to this record is the author's final peer reviewed version. The Publisher's final version can be found by following the DOI link.Existing assistive living and prompting based solutions have adopted a relatively complex approach to supporting individuals. These solutions have involved sensor based monitoring, activity recognition and assistance provisioning. Traditionally they have suffered from a number of issues rooted in scalability and performance levels associated with the activity recognition process. This paper introduces a simplistic approach to assistive living within a user's residence through the use of NFC tags and smart devices. The core concept of this approach is presented and is subsequently placed within the context of related work. A description of the architecture is provided and results following technical evaluation of the first system prototype are discussed