Insulin therapy in people with type 2 diabetes:opportunities and challenges?

Given the continued interest in defining the optimal management of individuals with type 2 diabetes, the Editor of Diabetes Care convened a working party of diabetes specialists to examine this topic in the context of insulin therapy. This was prompted by recent new evidence on the use of insulin in such people. The group was aware of evidence that the benefits of insulin therapy are still usually offered late, and thus the aim of the discussion was how to define the optimal timing and basis for decisions regarding insulin and to apply these concepts in practice. It was noted that recent evidence had built upon that of the previous decades, together confirming the benefits and safety of insulin therapy, albeit with concerns about the potential for hypoglycemia and gain in body weight. Insulin offers a unique ability to control hyperglycemia, being used from the time of diagnosis in some circumstances, when metabolic control is disturbed by medical illness, procedures, or therapy, as well as in the longer term in ambulatory care. For those previously starting insulin, various other forms of therapy can be added later, which offer complementary effects appropriate to individual needs. Here we review current evidence and circumstances in which insulin can be used, consider individualized choices of alternatives and combination regimens, and offer some guidance on personalized targets and tactics for glycemic control in type 2 diabetes. © 2014 by the American Diabetes Association.

(Table 1) Salinity and dissolved organic carbon concentration of marine water (ANT-XIX/2) and mangrove porewater (Brazil)

The chemical structure of refractory marine dissolved organic matter (DOM) is still largely unknown. Electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry (ESI FT-ICR-MS) was used to resolve the complex mixtures of DOM and provide valuable information on elemental compositions on a molecular scale. We characterized and compared DOM from two sharply contrasting aquatic environments, algal-derived DOM from the Weddell Sea (Antarctica) and terrigenous DOM from pore water of a tropical mangrove area in northern Brazil. Several thousand molecular formulas in the mass range of 300-600 Da were identified and reproduced in element ratio plots. On the basis of molecular elemental composition and double-bond equivalents (DBE) we calculated an average composition for marine DOM. O/C ratios in the marine samples were lower (0.36 ± 0.01) than in the mangrove pore-water sample (0.42). A small proportion of chemical formulas with higher molecular mass in the marine samples were characterized by very low O/C and H/C ratios probably reflecting amphiphilic properties. The average number of unsaturations in the marine samples was surprisingly high (DBE = 9.9; mangrove pore water: DBE = 9.4) most likely due to a significant contribution of carbonyl carbon. There was no significant difference in elemental composition between surface and deep-water DOM in the Weddell Sea. Although there were some molecules with unique marine elemental composition, there was a conspicuous degree of similarity between the terrigenous and algal-derived end members. Approximately one third of the molecular formulas were present in all marine as well as in the mangrove samples. We infer that different forms of microbial degradation ultimately lead to similar structural features that are intrinsically refractory, independent of the source of the organic matter and the environmental conditions where degradation took place.

Cash or non-cash: that is the question - the story of e-payment for social welfare in Ireland part 2

E-Government in its various forms and extensions, notably T-Government, is often presented as the panacea for resolving such complex social problems as social exclusion, lack of governance transparency, poor value for money and other ailments of modern societies. Yet, E-Government has not been adopted up to predicted levels. Many case studies investigating success factors, maturity models, and the application of acceptance models have been presented over the last 15 years, but a deep understanding of the potential impact and consequences of E-Government is still lacking. This is especially true for those initiatives that involve socio-economic and cultural contexts, which makes their evaluation and the prediction of their impact difficult. This paper reports on an on-going E-Government initiative in Ireland aimed at implementing E-payments for G2C, notably in the social welfare area. Three sets of personal surveys have been carried out to understand the perceived impact of governmental plans of moving from an almost fully cash-based payment system to a fully electronic based solution. Early results indicate that perceived pre-requisites for the planned change may be misleading. The impact on recipients’ lives cannot solely be measured in terms of economic gains: the consequences of such implementation may well reach further than expected.

Levi-flat Minimal Hypersurfaces in Two-dimensional Complex Space Forms

The purpose of this article is to classify the real hypersurfaces in complex space forms of dimension 2 that are both Levi-flat and minimal. The main results are as follows: When the curvature of the complex space form is nonzero, there is a 1-parameter family of such hypersurfaces. Specifically, for each one-parameter subgroup of the isometry group of the complex space form, there is an essentially unique example that is invariant under this one-parameter subgroup. On the other hand, when the curvature of the space form is zero, i.e., when the space form is complex 2-space with its standard flat metric, there is an additional `exceptional' example that has no continuous symmetries but is invariant under a lattice of translations. Up to isometry and homothety, this is the unique example with no continuous symmetries.

Annotated record of the detailed examination of Mn deposits from DSDP Site 160, Leg 16 (Cores 16-160-1, 16-160-2 and 16-160-3)

DSDP 160 forms part of a series of sites in the eastern equatorial Pacific on the west flank of the East Pacific Rise. Earlier legs of the Deep Sea Drilling Project, in particular Legs 5 and 9, have reported sediments rich in oxides of iron and perhaps other transition metals just above basement in the eastern Pacific. These occurrences roughly define a broad zone on the west flank of the rise. Site DSDP 160 lies on this trend and were selected by the Pacific Site Selection Panel to test the extent of such deposits.

Occurence of monothalamous foraminifera in Admiralty Bay, King George Island, West Antarctica (Table 1, 2)

During the late 2007 austral summer, 20 sediment samples were collected in Admiralty Bay (King George Island, South Shetlands, West Antarctica) from 8 down to 254 m water-depth (mwd). The samples yielded abundant assemblage of monothalamous benthic foraminifera, belonging to at least 40 morphospecies. They constituted the first such collection from Antarctic Peninsula fjords and provided a new insight into this group's diversity and distribution. Among organic-walled taxa, Psammophaga sp., Allogromia cf. crystallifera, and three morphotypes of Gloiogullmia were especially abundant. Agglutinated forms were dominated by Hippocrepinella hirudinea, Psammosphaera spp., Lagenammina spp., and various mudballs. Although, the majority of the morphotypes were known from other high?latitude locations, somewere reported for the first time. Our quantitative data (>125 µm) showed the greatest differences between monothalamous foraminifera assemblages at shallowest water depths above 50 mwd. The deepest assemblages from between 179 and 254 mwd, were most similar, suggesting uniform near-bottom conditions at ~200 mwd throughout the Admiralty Bay.

(Table 2) Stable carbon and oxygen isotope ratios of foraminifera of DSDP Holes 29-277 and 31-292

Oxygen isotopic studies both of benthic formanifera (Emiliani, 1954, doi:10.1126/science.119.3103.853; Savin et al., 1975, doi:10.1130/0016-7606(1975)86<1499:TMP>2.0.CO;2; Shackleton and Kennett, 1975, doi:10.2973/dsdp.proc.29.117.1975; Savin, 1977, doi:10.1146/annurev.ea.05.050177.001535) and shallow-marine carbonates ( Dorman, 1966; Devereux, 1967; Buchart, 1978, doi:10.1038/275121a0) have provided a useful monitor of marine palaeotemperatures. The Deep Sea Drilling Project (DSDP) has provided cores from many ocean basins to conduct detailed stable isotopic and palaeoceanographic studies of the Cenozoic and late Mesozoic. DSDP Sites 277 and 292, separated by ~60° latitude in Palaeogene times, each record an 18O enrichment in benthic foraminifera of nearly 1 per mil beginning at the Eocene-Oligocene boundary. Planktonic foraminiferal trends are similar to benthic trends in the high latitude southwest Pacific Ocean, but tropical planktonics show only a minor (~0.3 per mil) increase which may reflect a change in seawater composition. These results suggest a sudden cooling of Pacific deep waters and high latitude surface waters forms a useful stratigraphic marker for the Eocene-Oligocene boundary. This boundary is particularly important because of its association with several worldwide palaeo-oceanographic and biogeographic changes. These include a sudden drop in the calcite compensation depth of 1-2 km (van Andel et al., 1975; van Andel, 1975, doi:10.1016/0012-821X(75)90086-2); a decrease in planktonic microfossil diversity (Lipps, 1970, 10.2307/2406711; Kennett, 1978, doi:10.1016/0377-8398(78)90017-8; Sancetta, 1979, doi:10.1016/0377-8398(79)90025-2); a change in planktonic biogeographic patterns (Kennett, 1978, doi:10.1016/0377-8398(78)90017-8; Sancetta, 1979, doi:10.1016/0377-8398(79)90025-2; Haq and Lohmann, 1976, doi:10.1016/0377-8398(76)90008-6); and increased erosion of deep-sea sediments over wide areas (Kennet et al., 1972; Moore et al., 1978).

Structural and Functional Characterization of the Human Tribbles Homologue 2 Pseudokinase

The Tribbles Homologues are a family of three eukaryotic pseudokinases (Trb1, Trb2, Trb3) that act as allosteric inhibitors and regulatory scaffold sites in pathways governing adipogenesis, cell proliferation and insulin signaling. The Tribbles Homologues have the same overall tertiary structure of the eukaryotic protein kinase domain, but lack multiple residues necessary to catalysis in the nucleotide-binding P-loop and the Mg2+-coordinating DFG motif. Trb1 has been shown conclusively to be incapable of binding ATP, whereas a recent study presents evidence that Trb2 autophosphorylates independently of Mg2+ in vitro. This finding is surprising given the high degree of sequence similarity between the two proteins (71%), and suggests unique nucleotide binding and phosphotransfer mechanisms. The goal of this project was to investigate whether Trb2 possesses kinase activity or not and determine its structural basis. A method for the high-yield recombinant expression and purification of stable Trb2 was developed. Trb2 nucleotide binding and autophosphorylation could not be detected across multiple experimental approaches, including thermal shift assays, MANT-ATP fluorescence, radiolabeled phosphate incorporation, and nonspecific ATPase activity assays. Further characterization also revealed that Trb2 forms homomultimers with possible functional consequences, and extensive crystallization screening has yielded multiple promising conditions that could produce diffraction-quality crystals with further optimization. This project explores the difficulties in functionally characterizing putatively active pseudokinases, and proposes a structural basis for the conserved pseudokinase features of the Tribbles homologues.

Molecular mechanism of activation-triggered subunit exchange in Ca(2+)/calmodulin-dependent protein kinase II.

Activation triggers the exchange of subunits in Ca(2+)/calmodulin-dependent protein kinase II (CaMKII), an oligomeric enzyme that is critical for learning, memory, and cardiac function. The mechanism by which subunit exchange occurs remains elusive. We show that the human CaMKII holoenzyme exists in dodecameric and tetradecameric forms, and that the calmodulin (CaM)-binding element of CaMKII can bind to the hub of the holoenzyme and destabilize it to release dimers. The structures of CaMKII from two distantly diverged organisms suggest that the CaM-binding element of activated CaMKII acts as a wedge by docking at intersubunit interfaces in the hub. This converts the hub into a spiral form that can release or gain CaMKII dimers. Our data reveal a three-way competition for the CaM-binding element, whereby phosphorylation biases it towards the hub interface, away from the kinase domain and calmodulin, thus unlocking the ability of activated CaMKII holoenzymes to exchange dimers with unactivated ones.

Molecular mechanism of activation-triggered subunit exchange in Ca(2+)/calmodulin-dependent protein kinase II.

Activation triggers the exchange of subunits in Ca(2+)/calmodulin-dependent protein kinase II (CaMKII), an oligomeric enzyme that is critical for learning, memory, and cardiac function. The mechanism by which subunit exchange occurs remains elusive. We show that the human CaMKII holoenzyme exists in dodecameric and tetradecameric forms, and that the calmodulin (CaM)-binding element of CaMKII can bind to the hub of the holoenzyme and destabilize it to release dimers. The structures of CaMKII from two distantly diverged organisms suggest that the CaM-binding element of activated CaMKII acts as a wedge by docking at intersubunit interfaces in the hub. This converts the hub into a spiral form that can release or gain CaMKII dimers. Our data reveal a three-way competition for the CaM-binding element, whereby phosphorylation biases it towards the hub interface, away from the kinase domain and calmodulin, thus unlocking the ability of activated CaMKII holoenzymes to exchange dimers with unactivated ones.

The Genesis Of The Mycenaean Citadel: A Philosophical Quest For The Origins Of The Architectural Forms

This thesis deals with the origins of the architectural forms as expressed in the Homeric Mycenaean citadel. The Genesis of the Mycenaean Citadel is a philosophical quest which reveals the poetic dimension of the Mycenaean architecture. The Introduction deals with general theories on the subject of space, which converge into one, forming the spinal idea of the thesis. The ‘process of individuation’, the process by which a person becomes ‘in-dividual’ that is a separate, indivisible unity or ‘whole’, is a process of transformation and renewal which at collective level takes place within the citadel. This is built on the archetype which expresses both the nature of the soul as a microcosm and of the divinely ordered Cosmos. The confrontation of the rational ‘ego’ with the unconscious is the process which brings us to the ‘self’, that organising center of the human psyche which is symbolised through the centre of the citadel. . Chapter I refers to ‘the Archetype of the Mycenaean citadel’. The Mycenaean citadel, which is built on a certain pattern of placement and orientation in relation to landscape formations, reproduces images which belong to the category of the ‘archetypal mother’. On the other hand, its adjustment to a central point with ‘high’ significance, recalls the archetypal image of Shiva-Shakti. The citadel realises the concept of a Kantian ‘One-all embracing space’; it is a cosmogonic symbol but also a philosophical one. Chapter II examines the column in its dual meaning, which is expressed in one structure; column and capital unite within their symbolism the conscious and unconscious contents of the human psyche and express the archetype of wholeness and goal of the individuation process. 33 Chapter III is a philosophical research into the ‘symbolism of the triangle’, the sacred Pythagorean symbol which expresses certain cosmological beliefs about the relation between human nature and the divinely ordered Cosmos. The triangular slab over the Lion Gate is a representation of the Dionysiac ‘palingenesia’, that is the continuity of One life, which was central to the Mycenaean religion. Chapter IV deals with the tripartite ‘megaron’. The circular hearth within the four-columned hall expresses the ‘quaternity of the One’, one of the oldest religious symbols of humanity. Zeus is revealed in the ‘fiery monadic unit-cubit’ as an all-embracing god next to goddess Hestia, symbolised by the circular hearth. The ‘megaron’ expresses the alchemical quaternity and the triad but also the psychological stages of development in the process towards wholeness. In the Conclusions it is emphasised that the Mycenaean citadel was created as if in a repetition of a cosmogony. It is a ‘mandala’, the universal image which is identified with God-image in man. Moreover it is built in order to be experienced by its citizen in the process of his psychological transformation towards the ‘self’, the divine element within the psyche which unites with the divinely ordered Cosmos

Conceptualising public-private partnerships: a critical appraisal of approaches to meanings and forms

Purpose – The purpose of this paper is to survey various meanings attached to a public-private partnership (PPP) and related aspects in Western literature, and identify commonalities and differences between them. Additionally, the article intends to critically assess conflicting and overlapping views on contractual and institutional PPPs, their forms and models, and draw insights for transitional economies. Design/methodology/approach – The article contrasts and compares views on PPP meanings, forms and models within Western PPP literature, and also draws comparisons with understanding of partnership aspects in the Russian language sources. The paper examines theories underpinning PPPs, builds connections to PPP advantages and drawbacks, and provides critical assessment of net benefits that PPPs may bring along to the society. Findings – The article concludes that future PPP research in transitional countries such as Kazakhstan and Russia, particularly in the area of organisational and power arrangements in partnerships, may delineate new concepts such as government as a guarantor of a PPP project, social significance of a PPP project, and risk management in a country’s contextual environment. Practical implications – In transitional countries, in which PPPs are in their infancy, clarification of theoretical positions, and identification of commonalities and differences between meanings attached to the PPP terminology may enable better decisions by researchers and practitioners in their selection and further development of partnerships and related concepts. Originality/value – Research in the field of PPPs in transitional countries such as Russia and Kazakhstan is in its infancy. The paper intends to contribute to the body of knowledge about PPPs by providing detailed account and categorisation of their principal meanings, forms, models, underpinning theories, and drawing insights for future research in transitional countries.

On the reduction theory of binary forms

Cremona developed a reduction theory for binary forms of degree 3 and 4 with integer coefficients, the motivation in the case of quartics being to improve 2-descent algorithms for elliptic curves over Q. In this paper we extend some of these results to forms of higher degree. One application of this is to the study of hyperelliptic curves.

A importância do telemóvel na comunicação escrita, por SMS, de um grupo de alunos dos 2.º e 3.º ciclos

Dissertação de Mestrado, Ciências da Linguagem, Faculdade de Ciências Humanas e Sociais, Universidade do Algarve, 2015