The life of Sir Humphry Davy, bart., LL.D. : late president of the Royal Society, foreign associate of the Royal Institute of France, &c &c. &c. /

Memoirs communicated to the Royal Society, and works published during the author's life: v. 2, p. 450-456.

Reactions catalyzed by bacterial cytochromes P450

The cytochromes P450 are a large family of oxidative haemoproteins that are responsible for a wide variety of oxidative transformations in a variety of organisms. This review focuses upon the reactions catalyzed specifically by bacterial enzymes, which includes aliphatic hydroxylation, alkene epoxidation, aromatic hydroxylation, oxidative phenolic coupling, heteroatom oxidation and dealkylation, and multiple oxidations including C-C bond cleavage. The potential for the practical application of the oxidizing power of these enzymes is briefly discussed.

Crystal structure of P450cin in a complex with its substrate, 1,8-cineole, a close structural homologue to D-camphor, the substrate for P450cam

Cytochrome P450cin catalyzes the monooxygenation of 1,8-cineole, which is structurally very similar to D-camphor, the substrate for the most thoroughly investigated cytochrome P450, cytochrome P450cam. Both 1,8-cineole and D-camphor are C-10 monoterpenes containing a single oxygen atom with very similar molecular volumes. The cytochrome P450cin-substrate complex crystal structure has been solved to 1.7 Angstrom resolution and compared with that of cytochrome P450cam. Despite the similarity in substrates, the active site of cytochrome P450cin is substantially different from that of cytochrome P450cam in that the B' helix, essential for substrate binding in many cytochrome P450s including cytochrome P450cam, is replaced by an ordered loop that results in substantial changes in active site topography. In addition, cytochrome P450cin does not have the conserved threonine, Thr252 in cytochrome P450cam, which is generally considered as an integral part of the proton shuttle machinery required for oxygen activation. Instead, the analogous residue in cytochrome P450cin is Asn242, which provides the only direct protein H-bonding interaction with the substrate. Cytochrome P450cin uses a flavodoxin-like redox partner to reduce the heme iron rather than the more traditional ferredoxin-like Fe2S2 redox partner used by cytochrome P450cam and many other bacterial P450s. It thus might be expected that the redox partner docking site of cytochrome P450cin would resemble that of cytochrome P450BM3, which also uses a flavodoxin-like redox partner. Nevertheless, the putative docking site topography more closely resembles cytochrome P450cam than cytochrome P450BM3.

Structural basis for control of secondary vessels in the long-finned eel, Anguilla reinhardtii

Histological sections of primary segmental arteries and associated interarterial anastomoses and secondary vessels from the long-finned eel Anguilla reinhardtii were examined by light and transmission electron microscopy. Interarterial anastomoses were found to originate from the primary vasculature as depressions through the tunica intima and media, from where they ran perpendicularly to the adventitial layer, before coiling extensively. From here the anastomoses travelled a relatively linear path in the outer margin of the adventitia to anastomose with a secondary vessel running in parallel with the primary counterpart. In contrast to findings from other species, secondary vessels had a structure quite similar to that of primary vessels; they were lined by endothelial cells on a continuous basement membrane, with a single layer of smooth muscle cells surrounding the vessel. Smooth muscle cells were also found in the vicinity of interarterial anastomoses in the adventitia, but these appeared more longitudinally orientated. The presence of smooth muscle cells on all aspects of the secondary circulation suggests that this vascular system is regulated in a similar manner as the primary vascular system. Because interarterial anastomoses are structurally integrated with the primary vessel from which they originate, it is anticipated that flow through secondary vessels to some extent is affected by the vascular tone of the primary vessel. Immunohistochemical studies showed that primary segmental arteries displayed moderate immunoreactivity to antibodies against 5-hydroxytryptamine and substance P, while interarterial anastomoses and secondary vessels showed dense immunoreactivity. No immunoreactivity was observed on primary or secondary arteries against neuropeptide Y or calcitonin gene-related peptide.

Confirmation of the existence of alloparasitoids in nature - host relationships of an Australian Coccophagus species that parasitizes mealy bugs

Heteronomous hyperparasitoids are parasitic wasps with sex-related host relationships that are unique to a group of genera in the chalcidoid family Aphelinidae. Females are primary parasitoids of various sedentary bugs (mainly, scale insects, mealy bugs, and whiteflies). Males, in contrast, are hyperparasitic, and they frequently develop at the expense of female conspecifics. Alloparasitoids constitute a special category of heteronomous hyperparasitoids, for their males never develop through female conspecifics. The existence of alloparasitic host relationships and the utility of the category 'alloparasitoid' have both been questioned. Here, we present results that confirm the existence of the alloparasitic way of life among heteronomous aphelinids. We investigated an undescribed species of Coccophagus (Hymenoptera: Aphelinidae), an Australian parasitoid that attacks the introduced lantana mealy bug, Phenacoccus parvus Morrison (Homoptera: Pseudococcidae), in Queensland. A year-long field survey regularly returned large numbers of female Coccophagus spec. near gurneyi individuals from P. parvus (total n = 4212), but only few males (n = 11). Males emerged from samples only when the encyrtid parasitoid Anagyrus diversicornis (Howard) (Hymenoptera: Encyrtidae) was present in samples in relatively high numbers. Laboratory oviposition tests confirmed that A. diversicornis is a male host and showed that males do not develop at the expense of conspecific females. Other studies show that males are attracted in numbers to virgin females held in cages above mealy bug-infested Lantana montevidensis (Spreng.) Briq. (Verbenaceae) in the field, demonstrating that they are common in the population as a whole. This confirms that the males need hosts other than conspecific females and that their usual hosts are present outside of the lantana/P. parvus system. The implications of these results for developing a realistic classification of heteronomous host relationships are discussed.

Polymer fractionation by continuous chromatography

A review is given of general chromatographic theory, the factors affecting the performance of chromatographi c columns, and aspects of scale-up of the chromatographic process. The theory of gel permeation chromatography (g. p. c.) is received, and the results of an experimental study to optimize the performance of an analytical g.p.c. system are reported. The design and construction of a novel sequential continuous chromatographic refining unit (SCCR3), for continuous liquid-liquid chromatography applications, is described. Counter-current operation is simulated by sequencing a system of inlet and outlet port functions around a connected series of fixed, 5.1 cm internal diameter x 70 cm long, glass columns. The number of columns may be varied, and, during this research, a series of either twenty or ten columns was used. Operation of the unit for continuous fractionation of a dextran polymer (M. W. - 30,000) by g.p.c. is reported using 200-400 µm diameter porous silica beads (Spherosil XOB07S) as packing, and distilled water for the mobile phase. The effects of feed concentration, feed flow rate, and mobile and stationary phase flow rates have been investigated, by means of both product, and on-column, concentrations and molecular weight distributions. The ability to operate the unit successfully at on-column concentrations as high as 20% w/v dextran has been demonstrated, and removal of both high and low molecular weight ends of a polymer feed distribution, to produce products meeting commercial specifications, has been achieved. Equivalent throughputs have been as high as 2.8 tonnes per annum for ten columns, based on continuous operation for 8000 hours per annum. A concentration dependence of the equilibrium distribution coefficient, KD observed during continuous fractionation studies, is related to evidence in the literature and experimental results obtained on a small-scale batch column. Theoretical treatments of the counter-current chromatographic process are outlined, and a preliminary computer simulation of the SCCR3 unit t is presented.

Mechanisms of ion channel activation in primary cultured and clonal cell lines

The effects of hypotonic shock upon membrane C1 permeability of ROS 17/2.8 osteoblast-like cells was investigated using the patch-clamp technique. Hypotonic shock produced cell swelling that was accompanied by large amplitude, outwardly rectifying, currents that were active across the entire physiological range of membrane potentials (-80 to +100 mV). At strong depolarisations (> +50 mV) the currents exhibited time-dependent inactivation that followed a monoexponential time course. The currents were anion selective and exhibited a selectivity sequence of SCN- > I > Br- > Cl- > F- > gluconate. Current activation was unaffected by inhibitors of protein kinase (A (H-89) and tyrosine kinase (tyrphostin A25), and could not be mimicked by elevation of intracellular Ca2+ or activation of protein kinase C. Similarly, disruption of actin filaments by dihydrocytochalsin B, or generation of membrane tension by dipyridamole failed to elicit significant increases in cell chloride permeability. The mechanism of current activation is as yet undetermined. The currents were effectively inhibited by the chloride channel inhibitors NPPB and DIDS but resistant to DPC. A Cl- conductance with similar characteristics was found to be present in mouse primary cultured calvarial osteoblasts. The volume-sensitive Cl- current in ROS 17/2.8 cells was inhibited by arachidonic acid in two distinct phases. A rapid block that developed within 10 s, preceding a slower developing inhibitory phase that occurred approximately 90 s after onset of arachidonate superfusion. Arachidonic acid also induced kinetic modifications of the current which were evident as an acceleration of the time-dependent· inactivation exhibited at depolarised potentials. Inhibitors of cyclo-oxygenases, lipoxygenases and cytochrome P-4S0 were ineffectual against arachidonic acid's effects sugtgesting that arachidonic acid may elicit it's effects directly. Measurements of cell volume under hypotonic conditions showed that ROS 17/2,8 cells could effectively regulate their volume, However, effective inhibitors of the volume-sensitive CI" current drastically impaired this response suggesting that physiologically this current may have a vital role in cell volume regulation, In L6 skeletal myocytes, vasopressin was found to rapidiy hyperpolarise cells. This appears to occur as the result of activation of Ca2+ -sensitive K+ channels in a process dependent upon the presence of extracellular Ca2+.

Aminoglutethimide-induced leucopenia in a mouse model:effects of metabolic and structural determinates

A model of human leucopenia has been developed further in the female mouse. Following daily administration to female mice of 50 mg/kg of the aromatase inhibitor aminoglutethimide, significant falls in platelet and white cell counts occurred after 2 and 3 weeks. At week 4, drug dosage was stopped and the cell counts recovered at the end of that week, although on rechallenge at the beginning of week 5, both platelet and white cell counts fell rapidly. Administration to the mice of structural analogues of aminoglutethimide, such as WSP-3, glutethimide and 4-nitroglutethimide, showed no reductions in platelet and white cell counts. The haemotoxicity of aminoglutethimide over 21 days was unaffected by the presence of either the P-450 inhibitor SKF-525A or the hepatic P-450 inducer phenobarbitone. However, the co-administration of cimetidine abolished the haemotoxicity of aminoglutethimide in terms of platelet and white cell levels. In in vitro studies, both aminoglutethimide and WSP-3 were oxidised to cytotoxic species, although aminoglutethimide was significantly more cytotoxic than WSP-3. The NADPH-dependent covalent binding of 14C aminoglutethimide to mouse microsomes in vitro was significantly reduced by the presence of cimetidine. The activation of the compound to reactive species in vitro, the inhibitory effects of cimetidine in vivo and in vitro, as well as the rapid fall in the in vivo white cell count on rechallenge with aminoglutethimide suggest that this model illustrates a form of leucopenia which may be related to hapten formation and subsequent immune-mediated platelet and white cell lysis. © 2003 Elsevier B.V. All rights reserved.

Studying Recommender Systems to Enhance Distributed Computing Schedulers

Distributed Computing frameworks belong to a class of programming models that allow developers to

launch workloads on large clusters of machines. Due to the dramatic increase in the volume of

data gathered by ubiquitous computing devices, data analytic workloads have become a common

case among distributed computing applications, making Data Science an entire field of

Computer Science. We argue that Data Scientist's concern lays in three main components: a dataset,

a sequence of operations they wish to apply on this dataset, and some constraint they may have

related to their work (performances, QoS, budget, etc). However, it is actually extremely

difficult, without domain expertise, to perform data science. One need to select the right amount

and type of resources, pick up a framework, and configure it. Also, users are often running their

application in shared environments, ruled by schedulers expecting them to specify precisely their resource

needs. Inherent to the distributed and concurrent nature of the cited frameworks, monitoring and

profiling are hard, high dimensional problems that block users from making the right

configuration choices and determining the right amount of resources they need. Paradoxically, the

system is gathering a large amount of monitoring data at runtime, which remains unused.

In the ideal abstraction we envision for data scientists, the system is adaptive, able to exploit

monitoring data to learn about workloads, and process user requests into a tailored execution

context. In this work, we study different techniques that have been used to make steps toward

such system awareness, and explore a new way to do so by implementing machine learning

techniques to recommend a specific subset of system configurations for Apache Spark applications.

Furthermore, we present an in depth study of Apache Spark executors configuration, which highlight

the complexity in choosing the best one for a given workload.

Common Bound: The Small Groups of Methodism

The system of small groups John Wesley established to promote a proper life of discipleship in early Methodist converts was, in many respects, the strength of the Methodist movement. Those who responded to Wesley’s initial invitation to “flee the wrath to come” were organized into large gatherings called “societies,” which were then subdivided into smaller bands, class meetings, select societies, and penitent bands. The smaller groups gave Wesley the opportunity, through a system of appointed leaders, to keep track of the spiritual progress of every member in his movement, which grew to tens of thousands by the time of his death in 1791. As Methodism shifted from renewal movement to institutional church in the nineteenth century, however, growth slowed, and participation in such groups declined rapidly. By the early twentieth century, classes and bands were virtually extinct in every sector of Methodism save the African-American tradition. In recent years, scholars in various sectors of the Wesleyan tradition, particularly David Lowes Watson and Kevin Watson, have called for a recovery of these small groups for purposes of renewal in the church. There is no consensus, however, concerning what exactly contributed to the vitality of these groups during Wesley’s ministry.

Over the last century, sociological studies of group dynamics have revealed three common traits that are crucial to highly functioning groups: interdependence created by the existence of a common goal, interaction among group members that is “promotive” or cooperative in nature, and high levels of feedback associated with personal responsibility and individual accountability. All three of these were prevalent in the early Methodist groups. Interdependence existed around a shared goal, which for Wesley and the Methodists was holiness. That interdependence was cooperative in nature; individuals experienced the empowering grace of God as they each pursued the goal in the company of fellow pilgrims. Finally, the groups existed for purposes of feedback and accountability as individuals took responsibility both for themselves and others as they progressed together toward the goal of holy living. Wesley seemed to instinctively understand the essential nature of each of these characteristics in maintaining the vitality of the movement when he spoke of the importance of preserving the “doctrine, spirit and discipline” of early Methodism. Analysis of some of the present-day attempts to restore Wesley’s groups reveals frequent neglect to one or more of these three components. Perhaps most critical to recovering the vitality of the early Methodist groups will be reclaiming the goal of sanctification and coming to a consensus on what its pursuit means in the present day.

Avaliação da biomassa radicular fina em fragmentos florestais da Planície Costeira Fluminense.

As estimativas atuais de biomassa florestal contêm erros não dimensionados pela escassez de dados dos sistemas radiculares. Esta lacuna se deve às custosas estratégias de amostragem de raízes, que demanda grande quantidade de labor manual enquanto a estimativa da biomassa aérea pode ser feita com apenas a medida de diâmetro do tronco (DAP) conforme apontado por Chave et al, Houghton recomenda um valor geral de 20% da parte aérea para quantificar biomassa radicular, apesar de Silver haver demonstrado que o clima, o solo e a qualidade da serapilheira devam ser levados em conta. Dentre os principais determinantes da biomassa radicular destacam-se, no Estado do Rio de Janeiro, as contrastantes condições de clima e solo, além da composição e estrutura dos diferentes fragmentos florestais que ocorrem na paisagem. De acordo com Davis & Naghettini, ocorre expressiva variação climática representada por precipitações anuais desde 750 mm no Vale do Rio Paraíba do Sul a 4000 mm na Serra da Mantiqueira. Há grande variedade de solos no estado. A título de ilustração, em dois municípios costeiros, um deles incluído no presente estudo, Lumbreras et al encontraram a dominância, nas partes elevadas, de Latossolos, Argissolos, Nitossolos, Luvissolos, Planossolos, Cambissolos e Neossolos. Já nas baixadas, relacionadas aos sedimentos recentes, ocorrem as classes: Espodossolos, Planossolos, Gleissolos, Neossolos e Organossolos. Associados a outros atributos da feição paisagística, compuseram 45 unidades de mapeamentos. Nesse ambiente distribuem-se diversos fragmentos florestais, alguns remanescentes, em geral interferidos ou de difícil acesso e vegetação secundária em sua maioria. Os fragmentos florestais fluminenses resultam, primordialmente, da conversão das florestas nativas em cafezais e pastagens nos séculos 19 e 20, do uso crônico do fogo nas pastagens (ou por vandalismo), e da extração seletiva de árvores, cujo impacto pode ser detectado na ciclagem de nutrientes, conforme demonstrado por Villela et al., que deve influenciar significativamente a biomassa radicular. Ante o exposto o presente estudo visou estimar a biomassa radicular fina de diferentes fragmentos florestais da Planície Costeira Fluminense, comparando-as entre si.