Comparative effects of GLP-1 and GIP on cAMP production, insulin secretion, and in vivo antidiabetic actions following substitution of Ala8/Ala2 with 2-aminobutyric acid

The two major incretin hormones, glucagon-like peptide-1 (GLP-1), and glucose-dependent insulinotropic polypeptide (GIP), are currently being considered as prospective drug candidates for treatment of type 2 diabetes. Interest in these gut hormones was initially spurred by their potent insulinotropic activities, but a number of other antihyperglycaemic actions are now established. One of the foremost barriers in progressing GLP-1 and GIP to the clinic concerns their rapid degradation and inactivation by the ubiquitous enzyme, dipeptidyl peptidase IV (DPP IV). Here, we compare the DPP IV resistance and biological properties of Abu(8)/ Abu(2) (2-aminobutyric acid) substituted analogues of GLP-1 and GIP engineered to impart DPP IV resistance. Whereas (Abu(8))GLP-1 was completely stable to human plasma (half-life > 12h), GLP-1, GIP, and (Abu(2))GIP were rapidly degraded (half-lives: 6.2, 6.0, and 7.1 h, respectively). Native GIP, GLP-1, and particularly (Abu(8))GLP-1 elicited significant adenylate cyclase and insulinotropic activity, while (Abu(2))GIP was less effective. Similarly, in obese diabetic (ob/ob) mice, GIP, GLP-1, and (Abu(8))GLP-1 displayed substantial glucose-lowering and insulin -releasing activities, whereas (Abu(2))GIP was only weakly active. These studies illustrate divergent effects of penultimate amino acid Ala(8)/Ala(2) substitution with Abu on the biological properties of GLP-1 and GIP, suggesting that (Abu(8))GLP-1 represents a potential candidate for future therapeutic development. (C) 2004 Elsevier Inc. All rights reserved.

Half-precessional dynamics of monsoon rainfall near the East African Equator

External climate forcings-such as long-term changes in solar insolation-generate different climate responses in tropical and high latitude regions(1). Documenting the spatial and temporal variability of past climates is therefore critical for understanding how such forcings are translated into regional climate variability. In contrast to the data-richmiddle and high latitudes, high-quality climate-proxy records from equatorial regions are relatively few(2-4), especially from regions experiencing the bimodal seasonal rainfall distribution associated with twice-annual passage of the Intertropical Convergence Zone. Here we present a continuous and well-resolved climate-proxy record of hydrological variability during the past 25,000 years from equatorial East Africa. Our results, based on complementary evidence from seismic-reflection stratigraphy and organic biomarker molecules in the sediment record of Lake Challa near Mount Kilimanjaro, reveal that monsoon rainfall in this region varied at half-precessional (similar to 11,500-year) intervals in phase with orbitally controlled insolation forcing. The southeasterly and northeasterly monsoons that advect moisture from the western Indian Ocean were strengthened in alternation when the inter-hemispheric insolation gradient was at a maximum; dry conditions prevailed when neither monsoon was intensified and modest local March or September insolation weakened the rain season that followed. On sub-millennial timescales, the temporal pattern of hydrological change on the East African Equator bears clear high-northern-latitude signatures, but on the orbital timescale it mainly responded to low-latitude insolation forcing. Predominance of low-latitude climate processes in this monsoon region can be attributed to the low-latitude position of its continental regions of surface air flow convergence, and its relative isolation from the Atlantic Ocean, where prominent meridional overturning circulation more tightly couples low-latitude climate regimes to high-latitude boundary conditions.

Wavelength Dependence of Raman Enhancement from Gold Nanorod Arrays: Quantitative Experiment and Modeling of a Hot Spot Dominated System

Surface-enhanced Raman scattering (SERS) spectra from molecules adsorbed on the surface of vertically aligned gold nanorod arrays exhibit a variation in enhancement factor (EF) as a function of excitation wavelength that displays little correlation with the elastic optical properties of the surface. The key to understanding this lack of correlation and to obtaining agreement between experimental and calculated EF spectra lies with consideration of randomly distributed, sub-10 nm gaps between nanorods forming the substrate. Intense fields in these enhancement “hot spots” make a dominant contribution to the Raman scattering and have a very different spectral profile to that of the elastic optical response. Detailed modeling of the electric field enhancement at both excitation and scattering wavelengths was used to quantitatively predict both the spectral profile and the magnitude of the observed EF.

Aerospace Stiffened Panel Initial Sizing With Novel Skin Sub-Stiffening Features

The introduction of skin sub-stiffening features has the potential to modify the local stability and fatigue crack growth performance of stiffened panels. Proposed herein is a method to enable initial static strength sizing of panels with such skin sub-stiffening features. The method uses bespoke skin buckling coefficients, automatically generated by Finite Element analysis and thus limits the modification to the conventional aerospace panel initial sizing process. The approach is demonstrated herein and validated for prismatic sub-stiffening features. Moreover, examination of the generated buckling coefficient data illustrates the influence of skin sub-stiffening on buckling behavior, with static strength increases typically corresponding to a reduction in the number of initial skin longitudinal buckle half-waves.

HALF-CAVITY GENERATING SATURATED EMISSION AT 236 ANGSTROM IN GERMANIUM LASER

A half-cavity using a multilayer mirror has been set up close to the end of a large gain germanium-target system. An unambiguous saturation behaviour of the 232 angstrom and 236 angstrom lines has been observed. The role of the cavity mirror in this result is discussed. Suggestions are made for practical applications of an XUV laser in this wavelength range.

Northern peatland initiation lagged abrupt increases in deglacial atmospheric CH4

Peatlands are a key component of the global carbon cycle. Chronologies of peatland initiation are typically based on compiled basal peat radiocarbon (14C) dates and frequency histograms of binned calibrated age ranges. However, such compilations are problematic because poor quality 14C dates are commonly included and because frequency histograms of binned age ranges introduce chronological artefacts that bias the record of peatland initiation. Using a published compilation of 274 basal 14C dates from Alaska as a case study, we show that nearly half the 14C dates are inappropriate for reconstructing peatland initiation, and that the temporal structure of peatland initiation is sensitive to sampling biases and treatment of calibrated14C dates. We present revised chronologies of peatland initiation for Alaska and the circumpolar Arctic based on summed probability distributions of calibrated 14C dates. These revised chronologies reveal that northern peatland initiation lagged abrupt increases in atmospheric CH4 concentration at the start of the Bølling–Allerød interstadial (Termination 1A) and the end of the Younger Dryas chronozone (Termination 1B), suggesting that northern peatlands were not the primary drivers of the rapid increases in atmospheric CH4. Our results demonstrate that subtle methodological changes in the synthesis of basal 14C ages lead to substantially different interpretations of temporal trends in peatland initiation, with direct implications for the role of peatlands in the global carbon cycle.

Detonations in sub-chandrasekhar-mass C+O white dwarfs

Explosions of sub-Chandrasekhar-mass white dwarfs (WDs) are one alternative to the standard Chandrasekhar-mass model of Type Ia supernovae (SNe Ia). They are interesting since binary systems with sub-Chandrasekhar-mass primary WDs should be common and this scenario would suggest a simple physical parameter which determines the explosion brightness, namely the mass of the exploding WD. Here we perform one-dimensional hydrodynamical simulations, associated post-processing nucleosynthesis, and multi-wavelength radiation transport calculations for pure detonations of carbon-oxygen WDs. The light curves and spectra we obtain from these simulations are in good agreement with observed properties of SNe Ia. In particular, for WD masses from 0.97 to 1.15 Msun we obtain 56Ni masses between 0.3 and 0.8 Msun, sufficient to capture almost the complete range of SN Ia brightnesses. Our optical light curve rise times, peak colors, and decline timescales display trends which are generally consistent with observed characteristics although the range of B-band decline timescales displayed by our current set of models is somewhat too narrow. In agreement with observations, the maximum light spectra of the models show clear features associated with intermediate-mass elements and reproduce the sense of the observed correlation between explosion luminosity and the ratio of the Si II lines at ?6355 and ?5972. We therefore suggest that sub-Chandrasekhar-mass explosions are a viable model for SNe Ia for any binary evolution scenario leading to explosions in which the optical display is dominated by the material produced in a detonation of the primary WD. © 2010. The American Astronomical Society.

Double-detonation sub-Chandrasekhar supernovae: Synthetic observables for minimum helium shell mass models

In the double-detonation scenario for Type Ia supernovae, it is suggested that a detonation initiates in a shell of helium-rich material accreted from a companion star by a sub-Chandrasekhar-mass white dwarf. This shell detonation drives a shock front into the carbon-oxygen white dwarf that triggers a secondary detonation in the core. The core detonation results in a complete disruption of the white dwarf. Earlier studies concluded that this scenario has difficulties in accounting for the observed properties of Type Ia supernovae since the explosion ejecta are surrounded by the products of explosive helium burning in the shell. Recently, however, it was proposed that detonations might be possible for much less massive helium shells than previously assumed (Bildsten et al.). Moreover, it was shown that even detonations of these minimum helium shell masses robustly trigger detonations of the carbon-oxygen core (Fink et al.). Therefore, it is possible that the impact of the helium layer on observables is less than previously thought. Here, we present time-dependent multi-wavelength radiative transfer calculations for models with minimum helium shell mass and derive synthetic observables for both the optical and ? -ray spectral regions. These differ strongly from those found in earlier simulations of sub-Chandrasekhar-mass explosions in which more massive helium shells were considered. Our models predict light curves that cover both the range of brightnesses and the rise and decline times of observed Type Ia supernovae. However, their colors and spectra do not match the observations. In particular, their B - V colors are generally too red. We show that this discrepancy is mainly due to the composition of the burning products of the helium shell of the Fink et al. models which contain significant amounts of titanium and chromium. Using a toy model, we also show that the burning products of the helium shell depend crucially on its initial composition. This leads us to conclude that good agreement between sub-Chandrasekhar-mass explosions and observed Type Ia supernovae may still be feasible but further study of the shell properties is required.

Multiplex Solid-Phase PCR for Rapid Detection and Identification of Salmonella spp. at Sub-species

This study presents a solid-phase PCR (SP-PCR) for rapid detection, identification, and sub-typing of various Salmonella species, the major food-borne cause of salmonellosis. The target DNA is firstly amplified with PCR primers (one primer is labeled with fluorophores) in the liquid phase. Simultaneously on the solid phase, the amplified PCR amplicons interact with the nested DNA probes immobilized on the solid substrate as an array. If the immobilized probes match the sequence of the DNA templates they are extended by the polymerase and serve as template for the second strand elongation primed by the liquid phase primer thus generating new templates for the SP-PCR. After the reaction, PCR products labeled with fluorophores remain attached to the substrate and can be visualized directly by fluorescence readout devices. Using this method, S. enteritidis, S. typhimurium and S. dublin can be detected at the same time. The method offers several advantages over conventional multiplex PCR: less competition between different primer pairs thus increasing multiplexing capability, only single wavelength optical readout needed for the multiplexing detection, and less time-consuming owing to reduction of the post-PCR gel electrophoresis. The method will be useful for development of point-of-care devices for rapid detection and identification of Salmonella spp. A solid-phase PCR for rapid detection and identification of S. enteritidis, S. typhimurium and S. dublin is developed. The method offers advantages such as better multiplexing capability, only single wavelength optical readout needed, and less time-consuming.

Fluence dependence of the surface roughness of InP after N2 + bombardment

InP(1 0 0) surfaces were sputtered under ultrahigh vacuum conditions by 5 keV N2+ ions at an angle of incidence of 41° to the sample normal. The fluence, φ, used in this study, varied from 1 × 10¹⁴ to 5 × 10¹⁸ N2+ cm^-2. The surface topography was investigated using field emission scanning electron microscopy (FE-SEM) and atomic force microscopy (AFM). At the lower fluences (φ ≤ 5 × 10¹⁶ N2+ cm^-2) only conelike features appeared, similar in shape as was found for noble gas ion bombardment of InP. At the higher fluences, ripples also appeared on the surface. The bombardment-induced topography was quantified using the rms roughness. This parameter showed a linear relationship with the logarithm of the fluence. A model is presented to explain this relationship. The ripple wavelength was also determined using a Fourier transform method. These measurements as a function of fluence do not agree with the predictions of the Bradley-Harper theory. © 2004 Elsevier B.V. All rights reserved.

Avaliação dos parâmetros genéticos em progênies de meio-irmãos de uma sub-população de milho composto Flint para resistência à lagarta-da-espiga Helicoverpa zea (Bod.)

Foram estudadas 100 progênies de meio-irmãos de uma sub-população de milho (Zea mays L.) Composto Flint com o objetivo de avaliar a resistência de genótipos à lagarta-da-espiga Helicoverpa zea (Bod.). Foram obtidos os valores de danos médios da lagarta-da-espiga de 1,14 cm de comprimento na espiga determinado pela escala de Widstrom e coeficiente de variação experimental (CVE) de 23,4%. Dos parâmetros genéticos avaliados, a estimativa de herdabilidade (h²) foi de 6%, variância genética (VG) de 0,0015 cm² e variância fenotípica (VF) de 0,025 cm² para danos de H. zea. No entanto, o comprimento da ponta da bráctea e compactação da bráctea alcançaram resultados de herdabilidade de 75% e 72% respectivamente. Essa sub-população de milho apresenta variabilidade genética suficiente para utilização em programas de melhoramento, sendo que a resistência à lagarta-da-espiga pode ser obtida através da melhoria dos caracteres morfológicos diretamente relacionados à praga, como a compactação e comprimento da bráctea.

Filtros otimizados para transformadas seno, co-seno e de Hankel j0, j1 e j2

Apresentamos dois algoritmos automáticos, os quais se utilizam do método dos mínimos quadrados de Wiener-Hopf, para o cálculo de filtros lineares digitais para as transformadas seno, co-seno e de Hankel J₀, J₁ e J₂. O primeiro, que otimiza os parâmetros: incremento das abscissas, abscissa inicial e o fator de deslocamento utilizados para os cálculos dos coeficientes dos filtros lineares digitais que são aferidos através de transformadas co-seno, seno e o segundo, que otimiza os parâmetros: incremento das abscissas e abscissa inicial utilizados para os cálculos dos coeficientes dos filtros lineares digitais que são aferidos através de transformadas de Hankel J₀, J₁ e J₂. Esses algoritmos levaram às propostas de novos filtros lineares digitais de 19, 30 e 40 pontos para as transformadas co-seno e seno e de novos filtros otimizados de 37 , 27 e 19 pontos para as transformadas J₀, J₁ e J₂, respectivamente. O desempenho dos novos filtros em relação aos filtros existentes na literatura geofísica é avaliado usando-se um modelo geofísico constituído por dois semi-espaços. Como fonte usou-se uma linha infinita de corrente entre os semi-espaços originando, desta forma, transformadas co-seno e seno. Verificou-se melhores desempenhos na maioria das simulações usando o novo filtro co-seno de 19 pontos em relação às simulações usando o filtro co-seno de 19 pontos existente na literatura. Verificou-se também a equivalência de desempenhos nas simulações usando o novo filtro seno de 19 pontos em relação às simulações usando o filtro seno de 20 pontos existente na literatura. Adicionalmente usou-se também como fonte um dipolo magnético vertical entre os semi-espaços originando desta forma, transformadas J₀ e J₁, verificando-se melhores desempenhos na maioria das simulações usando o novo filtro J₁ de 27 pontos em relação ao filtro J₁ de 47 pontos existente na literatura. Verificou-se também a equivalência de desempenhos na maioria das simulações usando o novo filtro J₀ de 37 pontos em relação ao filtro J₀ de 61 pontos existente na literatura. Usou-se também como fonte um dipolo magnético horizontal entre os semi-espaços, verificando-se um desempenho análogo ao que foi descrito anteriormente dos novos filtros de 37 e 27 pontos para as respectivas transformadas J₀ e J₁ em relação aos filtros de 61 e 47 pontos existentes na literatura, destas respectivas transformadas. Finalmente verificou-se a equivalência de desempenhos entre os novos filtros J₀ de 37 pontos e J₁ de 27 pontos em relação aos filtros de 61 e 47 pontos existentes na literatura destas transformadas, respectivamente, quando aplicados em modelos de sondagens elétricas verticais (Wenner e Schlumberger). A maioria dos nossos filtros contêm poucos coeficientes quando comparados àqueles geralmente usados na geofísica. Este aspecto é muito importante porque transformadas utilizando filtros lineares digitais são usadas maciçamente em problemas numéricos geofísicos.

Characterization of monocarboxylate transporters (MCTs) expression in soft tissue sarcomas: distinct prognostic impact of MCT1 sub-cellular localization

Background: Soft tissue sarcomas (STSs) are a group of neoplasms, which, despite current therapeutic advances, still confer a poor outcome to half of the patients. As other solid tumors, STSs exhibit high glucose consumption rates, associated with worse prognosis and therapeutic response. As highly glycolytic tumors, we hypothesized that sarcomas should present an increased expression of lactate transporters (MCTs).Methods: Immunohistochemical expression of MCT1, MCT2, MCT4 and CD147 was assessed in a series of 86 STSs and the expression profiles were associated with patients' clinical-pathological parameters.Results: MCT1, MCT4 and CD147 were mainly observed in the plasma membrane of cancer cells (around 60% for MCTs and 40% for CD147), while MCT2 was conspicuously found in the cytoplasm (94.2%). Importantly, we observed MCT1 nuclear expression (32.6%). MCT1 and MCT4, alone or co-expressed with CD147 in the plasma membrane, were associated with poor prognostic variables including high tumor grade, disease progression and shorter overall survival. Conversely, we found MCT1 nuclear expression to be associated with low grade tumors and longer overall survival.Conclusions: The present work represents the first report of MCTs characterization in STSs. We showed the original finding of MCT1 expression in the nucleus. Importantly, opposite biological roles should be behind the dual sub-cellular localization of MCT1, as plasma membrane expression of MCT1 is associated with worse patients' prognosis, while nuclear expression is associated with better prognosis.

A Load-Balancing Shared-Protection-Path Reconfiguration Approach in WDM Wavelength-Routed Networks

Wavelength-routed networks (WRN) are very promising candidates for next-generation Internet and telecommunication backbones. In such a network, optical-layer protection is of paramount importance due to the risk of losing large amounts of data under a failure. To protect the network against this risk, service providers usually provide a pair of risk-independent working and protection paths for each optical connection. However, the investment made for the optical-layer protection increases network cost. To reduce the capital expenditure, service providers need to efficiently utilize their network resources. Among all the existing approaches, shared-path protection has proven to be practical and cost-efficient [1]. In shared-path protection, several protection paths can share a wavelength on a fiber link if their working paths are risk-independent. In real-world networks, provisioning is usually implemented without the knowledge of future network resource utilization status. As the network changes with the addition and deletion of connections, the network utilization will become sub-optimal. Reconfiguration, which is referred to as the method of re-provisioning the existing connections, is an attractive solution to fill in the gap between the current network utilization and its optimal value [2]. In this paper, we propose a new shared-protection-path reconfiguration approach. Unlike some of previous reconfiguration approaches that alter the working paths, our approach only changes protection paths, and hence does not interfere with the ongoing services on the working paths, and is therefore risk-free. Previous studies have verified the benefits arising from the reconfiguration of existing connections [2] [3] [4]. Most of them are aimed at minimizing the total used wavelength-links or ports. However, this objective does not directly relate to cost saving because minimizing the total network resource consumption does not necessarily maximize the capability of accommodating future connections. As a result, service providers may still need to pay for early network upgrades. Alternatively, our proposed shared-protection-path reconfiguration approach is based on a load-balancing objective, which minimizes the network load distribution vector (LDV, see Section 2). This new objective is designed to postpone network upgrades, thus bringing extra cost savings to service providers. In other words, by using the new objective, service providers can establish as many connections as possible before network upgrades, resulting in increased revenue. We develop a heuristic load-balancing (LB) reconfiguration approach based on this new objective and compare its performance with an approach previously introduced in [2] and [4], whose objective is minimizing the total network resource consumption.

Flares and variability from Sagittarius A(star): five nights of simultaneous multi-wavelength observations

Aims. We report on simultaneous observations and modeling of mid-infrared (MIR), near-infrared (NIR), and submillimeter (sub-mm) emission of the source Sgr A * associated with the supermassive black hole at the center of our Galaxy. Our goal was to monitor the activity of Sgr A* at different wavelengths in order to constrain the emitting processes and gain insight into the nature of the close environment of Sgr A*. Methods. We used the MIR instrument VISIR in the BURST imaging mode, the adaptive optics assisted NIR camera NACO, and the sub-mm antenna APEX to monitor Sgr A* over several nights in July 2007. Results. The observations reveal remarkable variability in the NIR and sub-mm during the five nights of observation. No source was detected in the MIR, but we derived the lowest upper limit for a flare at 8.59 mu m (22.4 mJy with A(8.59 mu m) = 1.6 +/- 0.5). This observational constraint makes us discard the observed NIR emission as coming from a thermal component emitting at sub-mm frequencies. Moreover, comparison of the sub-mm and NIR variability shows that the highest NIR fluxes (flares) are coincident with the lowest sub-mm levels of our five-night campaign involving three flares. We explain this behavior by a loss of electrons to the system and/or by a decrease in the magnetic field, as might conceivably occur in scenarios involving fast outflows and/or magnetic reconnection.