bluuebunny/crossref_metadata_2025 huggingface dataset:
Colonization of the Lesser Antilles by land birds
Authors: Ricklefs Robert E.
Published: June 2010

This study addresses characteristics of source and island populations of non‐raptorial land birds that have colonized the Lesser Antilles to determine whether colonization by individual source populations is a continuous process or occurs in transient phases. Species were classed as non‐colonists, recent colonists, old endemic residents in the Lesser Antilles, and old endemic taxa that had recently spread within the archipelago. If colonization were transient, source populations of recent colonists would be more widely distributed than source populations of older, endemic island species. I compared the ecological and geographic distributions of source populations and island populations for each of the colonization groups based on a variety of literature and field data. Ages of colonization events and spread within the islands were determined by sequence divergence in mitochondrial genes, where available; relative ages were otherwise inferred from taxonomic differentiation and gaps in island distribution.

Within the Lesser Antilles, old colonists, whether endemic or recently spread, tended to inhabit forest rather than open environments. Recently spread old colonists, like young colonists, had relatively greater abundance and broader habitat distribution within islands. These patterns were paralleled in northern South American source populations, but the trends were relatively weak. The strongest pattern was the propensity for source populations of young colonists and older, re‐expanded endemics to occur independently on islands off the Caribbean coast of Venezuela. In comparisons with non‐colonists in Trinidad, species that have recently colonized the Lesser Antilles tended to occur in more open habitats and to be more abundant locally, as well as more widespread through continental zoogeographical zones. Nested ANOVA based on a taxonomic hierarchy demonstrated that relative abundance and ecological and geographic distributions are labile, most of the variation being among species within genera. This is consistent with the idea that periods of high population productivity leading to colonization of offshore islands are transient. The existence of such phases can be inferred from correlations, albeit weak, between the status of populations in the Lesser Antilles and the ecological and geographic distribution of their putative source populations in the mainland.
Life‐history evolution in range‐shifting populations
Authors: Phillips Benjamin L. , Brown Gregory P. , Shine Richard
Published: June 2010

Most evolutionary theory does not deal with populations expanding or contracting in space. Invasive species, climate change, epidemics, and the breakdown of dispersal barriers, however, all create populations in this kind of spatial disequilibrium. Importantly, spatial disequilibrium can have important ecological and evolutionary outcomes. During continuous range expansion, for example, populations on the expanding front experience novel evolutionary pressures because frontal populations are assorted by dispersal ability and have a lower density of conspecifics than do core populations. These conditions favor the evolution of traits that increase rates of dispersal and reproduction. Additionally, lowered density on the expanding front eventually frees populations on the expanding edge from specialist, coevolved enemies, permitting higher investment into traits associated with dispersal and reproduction rather than defense against pathogens. As a result, the process of range expansion drives rapid life‐history evolution, and this seems to occur despite ongoing serial founder events that have complex effects on genetic diversity at the expanding front. Traits evolving on the expanding edge are smeared across the landscape as the front moves through, leaving an ephemeral signature of range expansion in the life‐history traits of a species across its newly colonized range. Recent studies suggest that such nonequilibrium processes during recent population history may have contributed to many patterns usually ascribed to evolutionary forces acting in populations at spatial equilibrium.
Internally driven alternation of functional traits in a multispecies predator–prey system
Authors: Tirok Katrin , Gaedke Ursula
Published: June 2010

The individual functional traits of different species play a key role for ecosystem function in aquatic and terrestrial systems. We modeled a multispecies predator–prey system with functionally different predator and prey species based on observations of the community dynamics of ciliates and their algal prey in Lake Constance. The model accounted for differences in predator feeding preferences and prey susceptibility to predation, and for the respective trade‐offs. A low food demand of the predator was connected to a high food selectivity, and a high growth rate of the prey was connected to a high vulnerability to grazing. The data and the model did not show standard uniform predator–prey cycles, but revealed both complex dynamics and a coexistence of predator and prey at high biomass levels. These dynamics resulted from internally driven alternations in species densities and involved compensatory dynamics between functionally different species. Functional diversity allowed for ongoing adaptation of the predator and prey communities to changing environmental conditions such as food composition and grazing pressure. The trade‐offs determined whether compensatory or synchronous dynamics occurred which influence the variability at the community level. Compensatory dynamics were promoted by a joint carrying capacity linking the different prey species which is particularly relevant at high prey biomasses, i.e., when grazers are less efficient. In contrast, synchronization was enhanced by the coupling of the different predator and prey species via common feeding links, e.g., by a high grazing pressure of a nonselective predator. The communities had to be functionally diverse in terms of their trade‐offs and their traits to yield compensatory dynamics. Rather similar predator species tended to cycle synchronously, whereas profoundly different species did not coexist. Compensatory dynamics at the community level thus required intermediately strong trade‐offs for functional traits in both predators and their prey.
Community genetic interactions mediate indirect ecological effects between a parasitoid wasp and rhizobacteria
Authors: Zytynska Sharon E. , Fleming Sarah , Tétard-Jones Catherine , Kertesz Michael A. , Preziosi Richard F.
Published: June 2010

Indirect ecological effects (IEEs) clearly influence species dynamics and abundance, yet relatively little is known about how they influence the evolution of species involved. While genetic variation in the species causing and responding to the IEE has obvious effects, the influence of genetic variation in intermediate species remains unexamined. Given the often counterintuitive responses of populations to IEEs this seems a significant omission. Following a community genetics approach, we used a model tetra‐trophic system (parasitoid wasp, aphid, barley, and rhizobacteria) to investigate the effect of genetic interactions within the two linking species (aphids and barley) on the IEE of rhizobacteria on wasps. We show that 12.4% of the variation in wasp size, a proxy for fitness, is explained by higher‐order interactions between aphid genotype (A), barley genotype (B), and presence or absence of rhizobacteria (R) (Genotype[B] × Genotype[A] × Environment[R]). Thus, the IEE of rhizobacteria on the parasitoid wasp is influenced by the specific combination of aphid and barley genotypes that mediate the interactions. In some cases changes in the genotypes of the intermediate species completely reverse the effect of rhizobacteria on wasp size. Our work demonstrates that within‐species genetic variation is important in shaping IEEs in communities, an essential component of community evolutionary processes.
Optimal Reinsurance for Variance Related Premium Calculation Principles
Authors: Guerra Manuel , Centeno Maria de Lourdes
Published: June 2010

This paper deals with numerical computation of the optimal form of reinsurance from the ceding company point of view, when the cedent seeks to maximize the adjustment coefficient of the retained risk and the reinsurance loading is an increasing function of the variance.

We compare the optimal treaty with the best stop loss policy. The optimal arrangement can provide a significant improvement in the adjustment coefficient when compared to the best stop loss treaty. Further, it is substantially more robust with respect to choice of the retention level than stop-loss treaties.
The Devil is in the Tails: Actuarial Mathematics and the Subprime Mortgage Crisis
Authors: Donnelly Catherine , Embrechts Paul
Published: June 2010

In the aftermath of the 2007-2008 financial crisis, there has been criticism of mathematics and the mathematical models used by the finance industry. We answer these criticisms through a discussion of some of the actuarial models used in the pricing of credit derivatives. As an example, we focus in particular on the Gaussian copula model and its drawbacks. To put this discussion into its proper context, we give a synopsis of the financial crisis and a brief introduction to some of the common credit derivatives and highlight the difficulties in valuing some of them.

We also take a closer look at the risk management issues in part of the insurance industry that came to light during the financial crisis. As a backdrop to this, we recount the events that took place at American International Group during the financial crisis. Finally, through our paper we hope to bring to the attention of a broad actuarial readership some “lessons (to be) learned” or “events not to be forgotten”.
Optimal Reinsurance Revisited – A Geometric Approach
Authors: Cheung Ka Chun
Published: June 2010

In this paper, we reexamine the two optimal reinsurance problems studied in Cai et al. (2008), in which the objectives are to find the optimal reinsurance contracts that minimize the value-at-risk (VaR) and the conditional tail expectation (CTE) of the total risk exposure under the expectation premium principle. We provide a simpler and more transparent approach to solve these problems by using intuitive geometric arguments. The usefulness of this approach is further demonstrated by solving the VaR-minimization problem when the expectation premium principle is replaced by Wang's premium principle.
On the Upcrossing and Downcrossing Probabilities of a Dual Risk Model With Phase-Type Gains
Authors: Ng Andrew C.Y.
Published: June 2010

In this paper, we consider the dual of the classical Cramér-Lundberg model when gains follow a phase-type distribution. By using the property of phase-type distribution, two pairs of upcrossing and downcrossing barrier probabilities are derived. Explicit formulas for the expected total discounted dividends until ruin and the Laplace transform of the time of ruin under a variety of dividend strategies can then be obtained without the use of Laplace transforms.
Pricing of Reinsurance Contracts in the Presence of Catastrophe Bonds
Authors: Haslip Gareth G. , Kaishev Vladimir K.
Published: June 2010

A methodology for pricing of reinsurance contracts in the presence of a catastrophe bond is developed. An important advantage of this approach is that it allows for the pricing of reinsurance contracts consistent with the observed market prices of catastrophe bonds on the same underlying risk process.

Within the proposed methodology, an appropriate financial pricing formula is derived, under a market implied risk neutral probability measure for both a catastrophe bond and an aggregate excess of loss reinsurance contract, using a generalised Fourier transform. Efficient numerical methods for the evaluation of this formula, such as the Fast Fourier transform and Fractional Fast Fourier transform, are considered.

The methodology is illustrated on several examples including Pareto and Gamma claim severities.
Comonotonic Approximations to Quantiles of Life Annuity Conditional Expected Present Values: Extensions to General Arima Models and Comparison with the Bootstrap
Authors: Denuit M. , Haberman S. , Renshaw A.E.
Published: June 2010

This paper aims to provide accurate approximations for the quantiles of the conditional expected present value of the payments made by the annuity provider, given the future path of the Lee-Carter time index. Conditional cohort and period life expectancies are also considered. The paper also addresses some associated simulation issues, which, hitherto, have been unresolved.
Bounded Relative Error Importance Sampling and Rare Event Simulation
Authors: McLeish Don L.
Published: June 2010

We consider estimating tail events using exponential families of importance sampling distributions. When the cannonical sufficient statistic for the exponential family mimics the tail behaviour of the underlying cumulative distribution function, we can achieve bounded relative error for estimating tail probabilities. Examples of rare event simulation from various distributions including Tukey's g&h distribution are provided.
Full abstraction for nominal general references
Authors: Tzevelekos Nikos
Published: June 2010

Game semantics has been used with considerable success in formulating fully abstract semantics for languages with higher-order procedures and a wide range of computational effects. Recently, nominal games have been proposed for modelling functional languages with names. These are ordinary, stateful games cast in the theory of nominal sets developed by Pitts and Gabbay. Here we take nominal games one step further, by developing a fully abstract semantics for a language with nominal general references.
A Type System For Call-By-Name Exceptions
Authors: Lebresne Sylvain
Published: June 2010

We present an extension of System F with call-by-name exceptions. The type system is enriched with two syntactic constructs: a union type for programs whose execution may raise an exception at top level, and a corruption type for programs that may raise an exception in any evaluation context (not necessarily at top level). We present the syntax and reduction rules of the system, as well as its typing and subtyping rules. We then study its properties, such as confluence. Finally, we construct a realizability model using orthogonality techniques, from which we deduce that well-typed programs are weakly normalizing and that the ones who have the type of natural numbers really compute a natural number, without raising exceptions.
Computation Tree Logic with Deadlock Detection
Authors: van Glabbeek Rob , Luttik Bas , Trcka Nikola
Published: June 2010

We study the equivalence relation on states of labelled transition systems of
satisfying the same formulas in Computation Tree Logic without the next state
modality (CTL-X). This relation is obtained by De Nicola & Vaandrager by
translating labelled transition systems to Kripke structures, while lifting the
totality restriction on the latter. They characterised it as divergence
sensitive branching bisimulation equivalence.
We find that this equivalence fails to be a congruence for interleaving
parallel composition. The reason is that the proposed application of CTL-X to
non-total Kripke structures lacks the expressiveness to cope with deadlock
properties that are important in the context of parallel composition. We
propose an extension of CTL-X, or an alternative treatment of non-totality,
that fills this hiatus. The equivalence induced by our extension is
characterised as branching bisimulation equivalence with explicit divergence,
which is, moreover, shown to be the coarsest congruence contained in divergence
sensitive branching bisimulation equivalence.
Micro structural control of stabilized Zirconia ceramics (8YSZ) through modified conventional sintering methodologies
Authors: Rajeswari K. , Reddy Rajasekhar , Hareesh U.S. , Saha B.P. , Johnson R.
Published: June 2010

Slip cast Y2O3 stabilized Zirconia (8YSZ) ceramics was subjected to Conventional Ramp and Hold (CRH), Rate Controlled (RCS) and Two Stage Sintering (2SS) methodologies. Sintered samples were characterized for their densities and grain size analysis by Scanning Electron Microscopy. The slip cast samples sintered by CRH and 2SS have achieved 98 - 99 % of theoretical densities while RCS samples have exhibited a low density of 97 %. The samples exhibited an average grain size of 2.64 ?m by 2SS sintering in comparison to 8.83 ?m in case of CRH and 3.45 ?m in case of RCS. Controlled pore growth associated with RCS, when compared to CRH methodology is mainly responsible for the relatively smaller grain size observed with RCS. A four fold decrease in grain size i.e. 2.64 ?m observed with the two step sintering can be attributed to the fact that the first heating step to high temperature of 1550?C for a shorter duration closes the porosity without significant grain growth. The second step at 1375?C for a longer period of time imparts densification with limited grain growth.
Modulation of Notch-1 Signaling Alleviates Vascular Endothelial Growth Factor–Mediated Diabetic Nephropathy
Authors: Lin Chun-Liang , Wang Feng-Sheng , Hsu Yen-Chen , Chen Cheng-Nan , Tseng Min-Jen , Saleem Moin A. , Chang Pey-Jium , Wang Jeng-Yi
Published: June 2010

OBJECTIVE

Disturbances in podocytes are typically associated with marked proteinuria, a hallmark of diabetic nephropathy. This study was conducted to investigate modulation of Notch-1 signaling in high glucose (HG)-stressed human podocytes and in a diabetic animal model.

RESEARCH DESIGN AND METHODS

Expression of the Notch signaling components was examined in HG-treated podocytes, human embryonic kidney cells (HEK293), and kidneys from diabetic animals by RT-qPCR, Western blot analysis, and immunohistochemical staining. The association between the Notch signaling, VEGF expression, and podocyte integrity was evaluated.

RESULTS

Notch-1 signaling was significantly activated in HG-cultured human podocytes and HEK293 cells and kidneys from diabetic animals. HG also augmented VEGF expression, decreasing nephrin expression and podocyte number—a critical event for the development of proteinuria in diabetic nephropathy. After use of pharmacological modulators or specific shRNA knockdown strategies, inhibition of Notch-1 signaling significantly abrogated VEGF activation and nephrin repression in HG-stressed cells and ameliorated proteinuria in the diabetic kidney.

CONCLUSIONS

Our findings suggest that upregulation of Notch-1 signaling in HG-treated renal podocytes induces VEGF expression and subsequent nephrin repression and apoptosis. Modulation of Notch-1 signaling may hold promise as a novel therapeutic strategy for the treatment of diabetic nephropathy.
Inhibition of De Novo Ceramide Synthesis Reverses Diet-Induced Insulin Resistance and Enhances Whole-Body Oxygen Consumption
Authors: Ussher John R. , Koves Timothy R. , Cadete Virgilio J.J. , Zhang Liyan , Jaswal Jagdip S. , Swyrd Suzanne J. , Lopaschuk David G. , Proctor Spencer D. , Keung Wendy , Muoio Deborah M. , Lopaschuk Gary D.
Published: June 2010

OBJECTIVE

It has been proposed that skeletal muscle insulin resistance arises from the accumulation of intramyocellular lipid metabolites that impede insulin signaling, including diacylglycerol and ceramide. We determined the role of de novo ceramide synthesis in mediating muscle insulin resistance.

RESEARCH DESIGN AND METHODS

Mice were subjected to 12 weeks of diet-induced obesity (DIO), and then treated for 4 weeks with myriocin, an inhibitor of serine palmitoyl transferase-1 (SPT1), the rate-limiting enzyme of de novo ceramide synthesis.

RESULTS

After 12 weeks of DIO, C57BL/6 mice demonstrated a doubling in gastrocnemius ceramide content, which was completely reversed (141.5 ± 15.8 vs. 94.6 ± 10.2 nmol/g dry wt) via treatment with myriocin, whereas hepatic ceramide content was unaffected by DIO. Interestingly, myriocin treatment did not alter the DIO-associated increase in gastrocnemius diacyglycerol content, and the only correlation observed between lipid metabolite accumulation and glucose intolerance occurred with ceramide (R = 0.61). DIO mice treated with myriocin showed a complete reversal of glucose intolerance and insulin resistance which was associated with enhanced insulin-stimulated Akt and glycogen synthase kinase 3β phosphorylation. Furthermore, myriocin treatment also decreased intramyocellular ceramide content and prevented insulin resistance development in db/db mice. Finally, myriocin-treated DIO mice displayed enhanced oxygen consumption rates (3,041 ± 124 vs. 2,407 ± 124 ml/kg/h) versus their control counterparts.

CONCLUSIONS

Our results demonstrate that the intramyocellular accumulation of ceramide correlates strongly with the development of insulin resistance, and suggests that inhibition of SPT1 is a potentially promising target for the treatment of insulin resistance.
Higher Plasma Soluble Receptor for Advanced Glycation End Products (sRAGE) Levels Are Associated With Incident Cardiovascular Disease and All-Cause Mortality in Type 1 Diabetes
Authors: Nin Johanna W.M. , Jorsal Anders , Ferreira Isabel , Schalkwijk Casper G. , Prins Martin H. , Parving Hans-Henrik , Tarnow Lise , Rossing Peter , Stehouwer Coen D.A.
Published: June 2010

OBJECTIVE

To investigate the associations of plasma levels of soluble receptor for advanced glycation end products (sRAGE) with incident cardiovascular disease (CVD) and all-cause mortality in type 1 diabetes and the extent to which any such associations could be explained by endothelial and renal dysfunction, low-grade inflammation, arterial stiffness, and advanced glycation end products (AGEs).

RESEARCH DESIGN AND METHODS

We prospectively followed 169 individuals with diabetic nephropathy and 170 individuals with persistent normoalbuminuria who were free of CVD at study entry and in whom levels of sRAGE and other biomarkers were measured at baseline. The median follow-up duration was 12.3 years (7.6–12.5).

RESULTS

The incidence of fatal and nonfatal CVD and all-cause mortality increased with higher baseline levels of log-transformed sRAGE (Ln-sRAGE) independently of other CVD risk factors: hazard ratio (HR) 1.90 (95% CI 1.13–3.21) and 2.12 (1.26–3.57) per 1-unit increase in Ln-sRAGE, respectively. Adjustments for estimated glomerular filtration rate (eGFRMDRD), but not or to a smaller extent for markers of endothelial dysfunction, low-grade inflammation, arterial stiffness, and AGEs, attenuated these associations to HR 1.59 (95% CI 0.91–2.77) for fatal and nonfatal CVD events and to 1.90 (1.09–3.31) for all-cause mortality. In addition, in patients with nephropathy, the rate of decline of GFR was 1.38 ml/min/1.73 m2 per year greater per 1-unit increase of Ln-sRAGE at baseline (P = 0.036).

CONCLUSIONS

Higher levels of sRAGE are associated with incident fatal and nonfatal CVD and all-cause mortality in individuals with type 1 diabetes. sRAGE-associated renal dysfunction may partially explain this association.
Functional Variants inMBL2Are Associated With Type 2 Diabetes and Pre-Diabetes Traits in Pima Indians and the Old Order Amish
Authors: Muller Yunhua L. , Hanson Robert L. , Bian Li , Mack Janel , Shi Xiaolian , Pakyz Ruth , Shuldiner Alan R. , Knowler William C. , Bogardus Clifton , Baier Leslie J.
Published: June 2010

OBJECTIVE

MBL2 encodes the mannose-binding lectin, which is a key player in the innate immune system and has recently been found to play a role in insulin resistance and development of type 1 diabetes and gestational diabetes mellitus. To assess the role of MBL2 in diabetes susceptibility, this gene was analyzed in the Pima Indian population, which has a high prevalence of type 2 diabetes.

RESEARCH DESIGN AND METHODS

Nineteen tag single nucleotide polymorphisms (SNPs) were genotyped in a population-based sample of 3,501 full-heritage Pima Indians, and selected SNPs were further genotyped in independent samples of Native American (n = 3,723) and Old Order Amish (n = 486) subjects.

RESULTS

Two variants, a promoter SNP (rs11003125) at −550 bp with a risk allele frequency of 0.77 and a Gly54Asp (rs1800450) with a risk allele frequency of 0.83, were associated with type 2 diabetes in the full-heritage Pima Indians (odds ratio 1.30 per copy of the G allele for rs1103125, P = 0.0007, and 1.30 per copy of the glycine allele for rs1800450, P = 0.002, adjusted for age, sex, birth year, and family membership). These associations replicated in an independent Native American sample (1.19, P = 0.04, for rs11003125) and a Caucasian sample, the Old Order Amish (1.51, P = 0.004, for rs1103125 and 2.38, P = 0.003, for rs1800450). Among Pima Indians with normal glucose tolerance, the diabetes risk allele glycine of Gly54Asp was associated with a decreased acute insulin response to an intravenous glucose bolus infusion (P = 0.004, adjusted for age, sex, percent body fat, glucose disposal under physiological insulin stimulation, and family membership).

CONCLUSIONS

Our data suggest that the functional variants in MBL2 contribute to type 2 diabetes susceptibility in both Native Americans and the Old Order Amish.
Deficiency of Rac1 Blocks NADPH Oxidase Activation, Inhibits Endoplasmic Reticulum Stress, and Reduces Myocardial Remodeling in a Mouse Model of Type 1 Diabetes
Authors: Li Jianmin , Zhu Huaqing , Shen E , Wan Li , Arnold J. Malcolm O. , Peng Tianqing
Published: June 2010

OBJECTIVE

Our recent study demonstrated that Rac1 and NADPH oxidase activation contributes to cardiomyocyte apoptosis in short-term diabetes. This study was undertaken to investigate if disruption of Rac1 and inhibition of NADPH oxidase would prevent myocardial remodeling in chronic diabetes.

RESEARCH DESIGN AND METHODS

Diabetes was induced by injection of streptozotocin in mice with cardiomyocyte-specific Rac1 knockout and their wild-type littermates. In a separate experiment, wild-type diabetic mice were treated with vehicle or apocynin in drinking water. Myocardial hypertrophy, fibrosis, endoplasmic reticulum (ER) stress, inflammatory response, and myocardial function were investigated after 2 months of diabetes. Isolated adult rat cardiomyocytes were cultured and stimulated with high glucose.

RESULTS

In diabetic hearts, NADPH oxidase activation, its subunits' expression, and reactive oxygen species production were inhibited by Rac1 knockout or apocynin treatment. Myocardial collagen deposition and cardiomyocyte cross-sectional areas were significantly increased in diabetic mice, which were accompanied by elevated expression of pro-fibrotic genes and hypertrophic genes. Deficiency of Rac1 or apocynin administration reduced myocardial fibrosis and hypertrophy, resulting in improved myocardial function. These effects were associated with a normalization of ER stress markers' expression and inflammatory response in diabetic hearts. In cultured cardiomyocytes, high glucose–induced ER stress was inhibited by blocking Rac1 or NADPH oxidase.

CONCLUSIONS

Rac1 via NADPH oxidase activation induces myocardial remodeling and dysfunction in diabetic mice. The role of Rac1 signaling may be associated with ER stress and inflammation. Thus, targeting inhibition of Rac1 and NADPH oxidase may be a therapeutic approach for diabetic cardiomyopathy.
Atrogin-1 Affects Muscle Protein Synthesis and Degradation When Energy Metabolism Is Impaired by the Antidiabetes Drug Berberine
Authors: Wang Huiling , Liu Dajun , Cao Peirang , Lecker Stewart , Hu Zhaoyong
Published: June 2010

OBJECTIVE

Defects in insulin/IGF-1 signaling stimulate muscle protein loss by suppressing protein synthesis and increasing protein degradation. Since an herbal compound, berberine, lowers blood levels of glucose and lipids, we proposed that it would improve insulin/IGF-1 signaling, blocking muscle protein losses.

RESEARCH DESIGN AND METHODS

We evaluated whether berberine ameliorates muscle atrophy in db/db mice, a model of type 2 diabetes, by measuring protein synthesis and degradation in muscles of normal and db/db mice treated with or without berberine. We also examined mechanisms for berberine-induced changes in muscle protein metabolism.

RESULTS

Berberine administration decreased protein synthesis and increased degradation in muscles of normal and db/db mice. The protein catabolic mechanism depended on berberine-stimulated expression of the E3 ubiquitin ligase, atrogin-1. Atrogin-1 not only increased proteolysis but also reduced protein synthesis by mechanisms that were independent of decreased phosphorylation of Akt or forkhead transcription factors. Impaired protein synthesis was dependent on a reduction in eIF3-f, an essential regulator of protein synthesis. Berberine impaired energy metabolism, activating AMP-activated protein kinase and providing an alternative mechanism for the stimulation of atrogin-1 expression. When we increased mitochondrial biogenesis by expressing peroxisome proliferator–activated receptor γ coactivator-1α, berberine-induced changes in muscle protein metabolism were prevented.

CONCLUSIONS

Berberine impairs muscle metabolism by two novel mechanisms. It impairs mitochonidrial function stimulating the expression of atrogin-1 without affecting phosphorylation of forkhead transcription factors. The increase in atrogin-1 not only stimulated protein degradation but also suppressed protein synthesis, causing muscle atrophy.
Spatiotemporal underwater light field fluctuations in the open ocean
Authors: Hieronymi Martin , Macke Andreas
Published: June 2010

The light availability in the upper layer of the open sea is subject to strong fluctuations due to focusing of surface waves. This paper shows measurements of downwelling spectral irradiances as well as spatiotemporal light field patterns along the water column. Results are interpreted with respect to diverse surface waves. Direct wind develops capillary and small gravity waves that affect the light regime only up to circa 5 m water depth. At high seas and below 5 m depth, light fluctuations can be described more accurately in terms of sea state parameters such as wave height and period, rather than wind speed. Between 3 m and 25 m water depth, waves with significant heights of 1.5 m to 2.5 m provoke the strongest intensity fluctuations. In general, fluctuation amplitudes decrease and periods extend with water depth where the coefficient of variation, CV, is in average four times higher above 2 m compared to 25 m water depth.
General formulation of digital in-line holography from correlation with a chirplet function
Authors: Coëtmellec S. , Verrier N. , Brunel M. , Lebrun D.
Published: June 2010

Digital in-line holography is revisited to propose a mathematical model that describes the recording-reconstruction process as a linear shift-invariant system with a pseudo-point spread function even when the images are out of the optimal plane in the sense of signal processing. A particular case is treated to show that the optimal plane is the best focus plane in the sense of optics. Next, an exact solution of the holographic reconstruction by correlation is given. By means of the previous results, we study the behavior of the result of the correlation function between the diffraction pattern function produced by an opaque disk and a chirplet function and between the diffraction pattern produced by a phase disk and the same chirplet function.
Christian Orientals in Conversation with Islam: Two Examples from German Mission History in the Late Nineteenth and Early Twentieth Centuries
Authors: Tamcke Martin
Published: June 2010

Abstract:

The writer describes experiences of Oriental Christians belonging to German missions dealing with Syriac-speaking Muslims in the late nineteenth and early twentieth centuries. Using the example of two prime Missions in the Urmia-region of Iran—the German Mission to the Orient and the Hermannsburger Mission—he establishes the difference between formally schooled, European-trained Christian rhetoricians, whose forum for debate was public and published, and the less flamboyant, native-born Christians in unpublished discussion with their fellow countrymen. Focus is on two types of encounter: a several-weeks-long published controversy, backed by Turkish political editor Edhem Ruhi but centred on the preaching and writing of Turkish Christian convert John Awetaranian; and the on-the-ground lessons learned by Pera Johannes and his associates at the Hermannsburg Mission in Wasirabad, as they engaged in tentative, non-inflammatory discussion with Muslims of a common cultural background. Both examples show the significance of political involvement, since, on the one hand, Ruhi's newspaper was a forum for his views and thus set into motion as well as called a halt to the Awetaranian-Islam debate, and on the other, the horror stories of the Hermannsburg Mission ultimately showed up the futility and perhaps foolhardiness of combatting culture, even as members of a tolerated minority. On the surface, Awetarian represents the product of self-assured literary activity engaging in open controversy in mission work; and Pera Johannes with the Hermannsburger demonstrates the relatively unlettered, despised native group of Christians in a tenuous situation. The two examples meet, historically, in their encountering realities of politics that could make or break their project.
Neurosurgeons' perspectives on psychosurgery and neuroenhancement: a qualitative study at one center
Authors: Mendelsohn Daniel , Lipsman Nir , Bernstein Mark
Published: June 2010

Object

Advances in the neurosciences are stirring debate regarding the ethical issues surrounding novel neurosurgical interventions. The application of deep brain stimulation (DBS) for treating refractory psychiatric disease, for instance, has introduced the prospect of altering disorders of mind and behavior and the potential for neuroenhancement. The attitudes of current and future providers of this technology and their position regarding its possible future applications are unknown. The authors sought to gauge the opinions of neurosurgical staff and trainees toward various uses of neuromodulation technology including psychosurgery and neuroenhancement.

Methods

The authors conducted a qualitative study involving in-depth interviews with 47 neurosurgery staff, trainees, and other neuroclinicians at a quaternary care center.

Results

Several general themes emerged from the interviews. These included universal support for psychosurgery given adequate informed consent and rigorous scientific methodology, as well as a relative consensus regarding the priority given to patient autonomy and the preservation of personal identity. Participants' attitudes toward the future use of DBS and other means of neuromodulation for cognitive enhancement and personality alteration revealed less agreement, although most participants felt that alteration of nonpathological traits is objectionable.

Conclusions

There is support in the neurosurgical community for the surgical management of refractory psychiatric disease. The use of neuromodulation for the alteration of nonpathological traits is morally and ethically dubious when it is out of sync with the values of society at large. Both DBS and neuromodulation will have far-reaching and profound public health implications.
Treatment with Angiotensin II Inhibitors and Residual Renal Function in Peritoneal Dialysis Patients
Authors: Kolesnyk Inna , Noordzij Marlies , Dekker Friedo W. , Boeschoten Elisabeth W. , Krediet Raymond T.
Published: June 2010

Background

Many studies have shown the renoprotective effect of angiotensin-converting enzyme inhibitors (ACEi) and angiotensin II receptor blockers (ARBs) in patients with chronic kidney disease stages I–IV. Two randomized controlled trials (RCTs) showed a positive effect of AII inhibitors on residual glomerular filtration rate (rGFR) in peritoneal dialysis (PD) patients. However, these studies were small and were performed in a highly selected group of PD patients. Our aim was to confirm the above findings in a larger number of prospectively followed PD patients.

Methods

First we analyzed the time course of decline of rGFR in 452 incident PD patients that were not anuric at the start of dialysis and that had structured follow-up data, with measurements at 3, 6, 12, 18, 24, 30, and 36 months after the start of dialysis. Changes in rGFR over time were analyzed with a linear mixed model for repeated measures. In addition, Cox regression models were used to estimate the risk of developing anuria. In a second approach, we aimed to repeat the above analyses in a selected group of patients that theoretically could have been randomized and therefore resembled the population studied in the 2 mentioned RCTs. In this group the follow-up was restricted to 1 year.

Results

201 patients were treated with ACEi/ARBs and 251 did not take these drugs at the start of PD. More patients from the treated group had diabetes and used more antihypertensive medications. The time course of decline of rGFR was not different between the 2 groups over the 3 years of PD treatment ( p = 0.52). Less than 25% of patients from each group became anuric and there was no difference in time to development of complete anuria between the treated and untreated groups. In the second approach, 130 patients were included: 37 were treated with ACEi/ARBs and 93 were not. Again, no difference was found between the 2 groups with respect to the rate of decline of rGFR and time of anuria development.

Conclusion

Our findings are not in line with the results of previous RCTs. The biggest limitation of observational studies is the inability to avoid confounding by indication. However, a RCT in such a setting also does not give a reliable answer. Given all the benefits of ACEi/ARBs, the medications should not be withheld from PD patients. However, their renoprotective effects may often be overruled by other factors influencing the time course of rGFR.
High Water Evaporation Rate is Associated with Low Blood Pressure in Chronic Peritoneal Dialysis Patients
Authors: Hwang Jyh-Chang , Kan Wei-Chih , Wang Charn-Ting
Published: June 2010

Background

The relationship between water evaporation rate (WER) and blood pressure (BP) in continuous ambulatory peritoneal dialysis (CAPD) patients has not been addressed before. This study was undertaken to evaluate the effects of WER on the BP and body weight (BW) of end-stage renal disease patients treated with CAPD.

Methods

Based on mean WER of each month, the year 2005 was divided into “high WER” and “low WER” stages. This study enrolled 66 CAPD patients at our center during 2005. The BP and BW of each patient were collected monthly. WER was measured with a class A evaporation pan.

Results

Compared to the high WER stage, CAPD patients had higher BP (systolic: 142 ± 29 vs 134 ± 27 mmHg, p < 0.001; diastolic: 86 ± 17 vs 84 ± 16 mmHg, p < 0.001) and BW (56.8 ± 10.2 vs 56.1 ± 10.2 kg, p < 0.001) in the low WER stage. Ambient temperature was significantly higher in the high WER stage ( p = 0.004) and it was also positively correlated with WER ( r = 0.82, p = 0.0012). Both mean BP ( r = –0.72, p = 0.0089) and BW ( r = –0.79, p = 0.002) showed inverse relationships to the WER. Moreover, both mean BP ( r = –0.95, p < 0.001) and BW ( r = –0.90, p < 0.001) also showed negative linear regressions to ambient temperature. There was a positive linear regression between mean BP and BW ( r = 0.85, p = 0.0004). Multiple linear regression analysis found that WER (β = –0.672, p = 0.026) was an independent factor correlated to patients’ mean BP.

Conclusions

CAPD patients had lower BP and BW in the high WER stage. These decreases were associated with higher ambient temperature and WER. We hypothesize that increased insensible salt and fluid loss secondary to high WER during hot seasons, especially in subtropical areas, ameliorates the hypervolemia and hypertension in CAPD patients.
Peritoneal Dialysis is not Associated with Myocardial Stunning
Authors: Selby Nicholas M. , McIntyre Christopher W.
Published: June 2010

Background

Hemodynamic changes during hemodialysis can precipitate subclinical myocardial ischemia, which over time contributes to the development of cardiac failure and is associated with a poor prognosis. Peritoneal dialysis (PD) is also associated with acute changes in systemic hemodynamics and a similarly high incidence of cardiovascular disease; we therefore sought to examine whether the hemodynamic effects of a PD exchange would be sufficient to induce subclinical myocardial ischemia.

Methods

10 patients on PD entered a prospective observational study to determine whether left ventricular (LV) regional wall motion abnormalities (RWMAs) developed following a dialysate exchange. Serial echocardiography with quantitative analysis was used to assess ejection fraction and regional systolic LV function (shortening fraction). Blood pressure (BP) and hemodynamic variables were measured using continuous pulse wave analysis.

Results

We observed a very low frequency of RWMA development (5/100 regions). Only 1 patient had more than 1 RWMA and 6 patients were entirely unaffected. Overall mean shortening fraction increased when comparing pre and post values for both 2-chamber (from 3.06% ± 1.5% to 4.26% ± 1.3%, p = 0.001) and 4-chamber (from 3.00% ± 0.7% to 3.67% ± 0.9%, p = 0.021) analyses. Mean arterial pressure fell by a small degree during drainage of dialysate, with a larger rise in BP observed during instillation. These changes were driven by changes in peripheral resistance that fell during drainage and rose during instillation.

Conclusions

In contrast to hemodialysis, the acute effects of PD do not result in subclinical myocardial ischemia.
Pharmacokinetics of once-daily Etravirine without and with Once-daily Darunavir/ritonavir in Antiretroviral-Naive HIV type-1-Infected Adults
Authors: DeJesus Edwin , Lalezari Jacob P , Osiyemi Olayemi O , Ruane Peter J , Ryan Robert , Kakuda Thomas N , Witek James
Published: June 2010

Background

A pharmacokinetic trial was conducted to evaluate the potential for once-daily etravirine in anti-retroviral regimens without and with darunavir/ritonavir.

Methods

During this multicentre, open-label, Phase IIa trial, treatment-naive patients aged ≥18 years with HIV type-1 (HIV-1) received etravirine 400 mg once daily with tenofovir disoproxil fumarate/emtricitabine 300/200 mg once daily from days 1–14; on days 15–28, darunavir/ritonavir 800/100 mg once daily was added. On day 29, etravirine was discontinued and patients continued with the other medications to day 42. Serial blood sampling for etravirine pharmacokinetics was performed over 24 h on day 14 and 28; patients fasted for ≥10 h prior to these visits.

Results

Of 23 enrolled patients (male 87%, Caucasian 39%), pharmacokinetic profiles for etravirine were available for 21 and 20 patients on day 14 and 28, respectively. The plasma concentration–time profile and pharmacokinetics for etravirine were unchanged with or without darunavir/ritonavir. The mean maximum plasma concentration (Cmax) was reached 4 h after administration and was 790 and 801 ng/ml on day 14 and 28, respectively; mean area under the plasma concentration–time curve (AUC) from before administration to 24 h after administration was 10,410 ng•h/ml on day 14 and 10,720 ng•h/ml on day 28. In a post-hoc analysis, etravirine Cmax was higher, minimum plasma concentration was lower and AUC was similar when compared with etravirine 200 mg twice daily.

Conclusions

Addition of darunavir/ritonavir to etravirine, all dosed once daily, did not have a clinically significant effect on the pharmacokinetics of etravirine. Findings support further investigation of etravirine 400 mg once daily in HIV-1-infected patients. (Trial registration number NCT00534352.)
New U-Pb zircon ages from the Flin Flon Targeted Geoscience Initiative Project 2006-2009: Flin Flon and Hook Lake blocks, Manitoba and Saskatchewan
Authors: Rayner N
Published: June 2010

New geochronological results indicate that the predominant age of Flin Flon block volcanism is ca. 1890 Ma. A volcanic breccia within the Millrock member yields a maximum age of 1889 ± 9 Ma. A rhyolite flow at Millrock Hill yields a crystallization age of
1888.9 ± 1.6 Ma. The age of rhyolite at the Flin Flon mine South Main shaft is revised to 1887.1 ± 2.2 Ma. Lapilli tuff at Hilary Lake is dated at 1886 ± 4 Ma. A weakly foliated intermediate dyke is dated at 1872 ± 7 Ma, indicating early deformation. A porphyritic leucocratic
granite dyke provides a minimum age for post-Missi folding of 1840 ± 8 Ma north of the Club Lake fault. The maximum age of shearing is constrained by a felsic dyke at 1839 +6/-2 Ma. The western sequence of the Hook Lake block is constrained by a crystallization age of 1891 ± 17 Ma and a
minimum age of 1888.1 ± 0.9 Ma. Altered rhyolite from the eastern sequence is dated at 1882.0 ± 1.0 Ma.
The criteria used by private general practitioners in Bloemfontein for the diagnosis and referral of asthma patients aged 6–15 years
Authors: Balt Monia , Joubert Caroline , Nel Michelle , Solomon Lincoln J. , Joubert Gina
Published: June 2010

Background: Participants in the study were general practitioners (GPs) in private practice in Bloemfontein, South Africa.Objectives: To determine and evaluate the criteria employed by GPs in Bloemfontein to diagnose and refer chronic and acute asthma patients aged 6–15 years and to investigate the actual diagnostic criteria used by GPs, as compared to the theoretical (i.e. textbook) criteria.Method: A descriptive study was performed. A questionnaire was designed to investigate which methods of diagnosis were employed by GPs with regard to childhood asthma. The questionnaire was distributed to GPs who fulfilled certain inclusion criteria and were selected by means of simple random sampling. Statistical analysis of data was done by the Department of Biostatistics, University of the Free State, and results were summarised as frequencies and percentages.Results: Certain elements were lacking with regard to the patients’ histories taken by GPs. These included severity and frequency of attacks, as well as precipitating factors, such as smoking in the family and allergies. A worrisome number of GPs did not seem to be aware of the exact clinical picture of asthma in children and some failed to use the prescribed guidelines proposed for diagnosis of this condition in young patients. Most GPs indicated that they refer asthmatic children to private specialists, although this practice depended on the medical aid status of the patient’s parents/guardian.Conclusion: As portrayed by the feedback obtained from these Bloemfontein-based GPs, it could be presumed that the diagnosis of asthma in children did not always meet the standard criteria.