Cloning, functional expression, and chromosomal localization of the human pancreatic islet glucose-dependent insulinotropic polypeptide receptor.

Glucose-dependent insulinotropic polypeptide (GIP) is a hormone secreted by the endocrine K-cells from the duodenum that stimulates glucose-induced insulin secretion. Here, we present the molecular characterization of the human pancreatic islet GIP receptor. cDNA clones for the GIP receptor were isolated from a human pancreatic islet cDNA library. They encoded two different forms of the receptor, which differed by a 27-amino acid insertion in the COOH-terminal cytoplasmic tail. The receptor protein sequence was 81% identical to that of the rat GIP receptor. When expressed in Chinese hamster lung fibroblasts, both forms of the receptor displayed high-affinity binding for GIP (180 and 600 pmol/l). GIP binding was displaced by < 20% by 1 mumol/l glucagon, glucagon-like peptide (GLP-I)(7-36) amide, vasoactive intestinal peptide, and secretin. However exendin-4 and exendin-(9-39) at 1 mumol/l displaced binding by approximately 70 and approximately 100% at 10 mumol/l. GIP binding to both forms of the receptor induced a dose-dependent increase in intracellular cAMP levels (EC50 values of 0.6-0.8 nmol/l) but no elevation of cytoplasmic calcium concentrations. Interestingly, both exendin-4 and exendin-(9-39) were antagonists of the receptor, inhibiting GIP-induced cAMP formation by up to 60% when present at a concentration of 10 mumol/l. Finally, the physical and genetic chromosomal localization of the receptor gene was determined to be on 19q13.3, close to the ApoC2 gene. These data will help study the physiology and pathophysiology of the human GIP receptor.

Frontshear and backshear instabilities of the mean longshore current

An analytical model based on Bowen and Holman [1989] is used to prove the existence of instabilities due to the presence of a second extremum of the background vorticity at the front side of the longshore current. The growth rate of the so-called frontshear waves depends primarily upon the frontshear but also upon the backshear and the maximum and the width of the current. Depending on the values of these parameters, either the frontshear or the backshear instabilities may dominate. Both types of waves have a cross-shore extension of the order of the width of the current, but the frontshear modes are localized closer to the coast than are the backshear modes. Moreover, under certain conditions both unstable waves have similar growth rates with close wave numbers and angular frequencies, leading to the possibility of having modulated shear waves in the alongshore direction. Numerical analysis performed on realistic current profiles confirm the behavior anticipated by the analytical model. The theory has been applied to a current profile fitted to data measured during the 1980 Nearshore Sediment Transport Studies experiment at Leadbetter Beach that has an extremum of background vorticity at the front side of the current. In this case and in agreement with field observations, the model predicts instability, whereas the theory based only on backshear instability fai led to do so.

Measurement of the mechanical power of walking by satellite positioning system (GPS).

PURPOSE: This descriptive article illustrates the application of Global Positioning System (GPS) professional receivers in the field of locomotion studies. The technological challenge was to assess the external mechanical work in outdoor walking. METHODS: Five subjects walked five times during 5 min on an athletic track at different imposed stride frequency (from 70-130 steps x min(-1)). A differential GPS system (carrier phase analysis) measured the variation of the position of the trunk at 5 Hz. A portable indirect calorimeter recorded breath-by-breath energy expenditure. RESULTS: For a walking speed of 1.05 +/- 0.11 m x s(-1), the vertical lift of the trunk (43 +/- 14 mm) induced a power of 46.0 +/- 20.4 W. The average speed variation per step (0.15 +/- 0.03 m x s(-1)) produced a kinetic power of 16.9 +/- 7.2 W. As compared with commonly admitted values, the energy exchange (recovery) between the two energy components was low (39.1 +/- 10.0%), which induced an overestimated mechanical power (38.9 +/- 18.3 W or 0.60 W x kg(-1) body mass) and a high net mechanical efficiency (26.9 +/- 5.8%). CONCLUSION: We assumed that the cause of the overestimation was an unwanted oscillation of the GPS antenna. It is concluded that GPS (in phase mode) is now able to record small body movements during human locomotion, and constitutes a promising tool for gait analysis of outdoor unrestrained walking. However, the design of the receiver and the antenna must be adapted to human experiments and a thorough validation study remains to be conducted.

Study and modeling of the desintegration kinetics of coated paper

The disintegration of recovered paper is the first operation in the preparation of recycled pulp. It is known that the defibering process follows a first order kinetics from which it is possible to obtain the disintegration kinetic constant (KD) by means of different ways. The disintegration constant can be obtained from the Somerville index results (%lsv and from the dissipated energy per volume unit (Ss). The %slv is related to the quantity of non-defibrated paper, as a measure of the non-disintegrated fiber residual (percentage of flakes), which is expressed in disintegration time units. In this work, disintegration kinetics from recycled coated paper has been evaluated, working at 20 revise rotor speed and for different fiber consistency (6, 8, 10, 12 and 14%). The results showed that the values of experimental disintegration kinetic constant, Ko, through the analysis of Somerville index, as function of time. Increased, the disintegration time was drastically reduced. The calculation of the disintegration kinetic constant (modelled Ko), extracted from the Rayleigh’s dissipation function, showed a good correlation with the experimental values using the evolution of the Somerville index or with the dissipated energy

Fate of the herbicide glyphosate and its metabolite AMPA in soils and their transfer to surface waters: A multi-scale approach in the Lavaux vineyards, western Switzerland

The use of herbicides in agriculture may lead to environmental problems, such as surface water pollution, with a potential risk for aquatic organisms. The herbicide glyphosate is the most used active ingredient in the world and in Switzerland. In the Lavaux vineyards it is nearly the only molecule applied. This work aimed at studying its fate in soils and its transfer to surface waters, using a multi-scale approach: from molecular (10-9 m) and microscopic scales (10-6 m), to macroscopic (m) and landscape ones (103 m). First of all, an analytical method was developed for the trace level quantification of this widely used herbicide and its main by-product, aminomethylphosphonic acid (AMPA). Due to their polar nature, their derivatization with 9-fluorenylmethyl chloroformate (FMOC-Cl) was done prior to their concentration and purification by solid phase extraction. They were then analyzed by ultra performance liquid chromatography coupled with tandem mass spectrometry (UPLC-MS/MS). The method was tested in different aqueous matrices with spiking tests and validated for the matrix effect correction in relevant environmental samples. Calibration curves established between 10 and 1000ng/l showed r2 values above 0.989, mean recoveries varied between 86 and 133% and limits of detection and quantification of the method were as low as 5 and 10ng/l respectively. At the parcel scale, two parcels of the Lavaux vineyard area, located near the Lutrive River at 6km to the east of Lausanne, were monitored to assess to which extent glyphosate and AMPA were retained in the soil or exported to surface waters. They were equipped at their bottom with porous ceramic cups and runoff collectors, which allowed retrieving water samples for the growing seasons 2010 and 2011. Results revealed that the mobility of glyphosate and AMPA in the unsaturated zone was likely driven by the precipitation regime and the soil characteristics, such as slope, porosity structure and layer permeability discrepancy. Elevated glyphosate and AMPA concentrations were measured at 60 and 80 cm depth at parcel bottoms, suggesting their infiltration in the upper parts of the parcels and the presence of preferential flow in the studied parcels. Indeed, the succession of rainy days induced the gradual saturation of the soil porosity, leading to rapid infiltration through macropores, as well as surface runoff formation. Furthermore, the presence of more impervious weathered marls at 100 cm depth induced throughflows, the importance of which for the lateral transport of the herbicide molecules was determined by the slope steepness. Important rainfall events (>10 mm/day) were clearly exporting molecules from the soil top layer, as indicated by important concentrations in runoff samples. A mass balance showed that total loss (10-20%) mainly occurred through surface runoff (96%) and, to a minor extent, by throughflows in soils (4%), with subsequent exfiltration to surface waters. Observations made in the Lutrive River revealed interesting details of glyphosate and AMPA dynamics in urbanized landscapes, such as the Lavaux vineyards. Indeed, besides their physical and chemical properties, herbicide dynamics at the catchment level strongly depend on application rates, precipitation regime, land use and also on the presence of drains or constructed channels. Elevated concentrations, up to 4970 ng/l, observed just after the application, confirmed the diffuse export of these compounds from the vineyard area by surface runoff during main rain events. From April to September 2011, a total load of 7.1 kg was calculated, with 85% coming from vineyards and minor urban sources and 15% from arable crops. Small vineyard surfaces could generate high concentrations of herbicides and contribute considerably to the total load calculated at the outlet, due to their steep slopes (~10%). The extrapolated total amount transferred yearly from the Lavaux vineyards to the Lake of Geneva was of 190kg. At the molecular scale, the possible involvement of dissolved organic matter (DOM) in glyphosate and copper transport was studied using UV/Vis fluorescence spectroscopy. Combined with parallel factor (PARAFAC) analysis, this technique allowed characterizing DOM of soil and surface water samples from the studied vineyard area. Glyphosate concentrations were linked to the fulvic-like spectroscopic signature of DOM in soil water samples, as well as to copper, suggesting the formation of ternary complexes. In surface water samples, its concentrations were also correlated to copper ones, but not in a significant way to the fulvic-like signature. Quenching experiments with standards confirmed field tendencies in the laboratory, with a stronger decrease in fluorescence intensity for fulvic-like fluorophore than for more aromatic ones. Lastly, based on maximum concentrations measured in the river, an environmental risk for these compounds was assessed, using laboratory tests and ecotoxicity data from the literature. In our case and with the methodology applied, the risk towards aquatic species was found negligible (RF<1).

Laboratory Study of the Leachate from Crushed Portland Cement Concrete Base Material, MLR-96-04, 1999

Since the 1980s, the Iowa Department of Transportation has increased its use of recycled Portland Cement Concrete (PCC) as drainable base material below some new pavements. Water flowing out of the longitudinal drains on projects having recycled PCC drainable bases was found to have a high pH value. The high pH water impedes vegetation growth and becomes a contributing factor to soil erosion at the drain outlet. In addition, the high pH water contributes to the growth of crystalline deposits on the drain outlet wire mesh rodent guard and in some cases caused it to become completely blocked. This research determined which of three choices of recycled PCC drainable base material, gradation, and design would give the lowest pH value in the drain discharge water. The drainable base material having its fines separated out and placed as a 2-in. (5.1-mm) bottom layer, below the remaining coarse material, generally gave pH values around 11.2 while other designs tested gave pH values around 11.5.

Study and modeling of the desintegration kinetics of coated paper

The disintegration of recovered paper is the first operation in the preparation of recycled pulp. It is known that the defibering process follows a first order kinetics from which it is possible to obtain the disintegration kinetic constant (KD) by means of different ways. The disintegration constant can be obtained from the Somerville index results (%lsv and from the dissipated energy per volume unit (Ss). The %slv is related to the quantity of non-defibrated paper, as a measure of the non-disintegrated fiber residual (percentage of flakes), which is expressed in disintegration time units. In this work, disintegration kinetics from recycled coated paper has been evaluated, working at 20 revise rotor speed and for different fiber consistency (6, 8, 10, 12 and 14%). The results showed that the values of experimental disintegration kinetic constant, Ko, through the analysis of Somerville index, as function of time. Increased, the disintegration time was drastically reduced. The calculation of the disintegration kinetic constant (modelled Ko), extracted from the Rayleigh’s dissipation function, showed a good correlation with the experimental values using the evolution of the Somerville index or with the dissipated energy

Steady State Concentrations of the Enantiomers of Mianserin and Desmethylmianserin in Poor and in Homozygous and Heterozygous Extensive Metabolizers of Debrisoquine.

AB Summary: Steady state concentrations of (S)- and (R)-mianserin and desmethylmianserin were measured in 21 homozygous extensive metabolizers (as determined by genotyping for mutations 3 [or A] and 4 [or B]), in seven heterozygous extensive metabolizers and in one poor metabolizer of debrisoquine, as well as in one patient receiving very high doses of mianserin (360 mg/day) and fluoxetine (160 mg/day), a strong cytochrome P450IID6 inhibitor. The mean dose of mianserin was (mean +/- SD, range: 67 +/- 63, 10 to 360 mg/day). High dispersions of the (S)/(R)-mianserin and desmethylmianserin ratios were observed (mean +/- SD, range: 2.10+/- 1.01, 0.64 to 4.76, and 0.29 +/- 0.14, 0.08 to 0.57, respectively). The highest (S)/(R)-mianserin ratio was calculated for the poor metabolizer (4.76) agreeing with those results of a single-dose study with poor and extensive metabolizers of debrisoquine, in that the cytochrome P450IID6 is probably involved in the metabolism of mianserin with an enantioselectivity for the (S)-enantiomer. Nevertheless, the mean concentration-to-dose ratios for (S)- or (R)-mianserin or desmethylmianserin were not significantly different between homozygous and heterozygous extensive metabolizers, and no particular values were measured in the poor metabolizer nor in the patient receiving fluoxetine. Furthermore, the(S)/(R)-mianserin ratio measured in the PM was only slightly higher than the second highest ratio (3.85) of an homozygous extensive metabolizer, whereas no particular value (2.92) was calculated for the patient taking fluoxetine. Finally, no significant differences in (S)/(R)-mianserin or(S)/(R)-desmethylmianserin were calculated between homozygous and heterozygous extensive metabolizers. Although the number of patients included in this study is too low to allow definite conclusions, the results suggest that the debrisoquine genotype has only a moderate influence on the steady state concentrations of the enantiomers of mianserin and desmethylmianserin. (C) Lippincott-Raven Publishers

Hematological, biochemical and ruminant parameters for diagnosis of left displacement of the abomasum in dairy cows from Southern Brazil

The objective of this work was to evaluate hematological, biochemical and ruminant parameters for diagnosis and treatment of the left displaced abomasum (LDA) in dairy cows, in the Plateau Region of Rio Grande do Sul, Brazil. Ruminant fluid, blood and urine samples were collected from 20 cows suffering LDA and from 20 healthy cows (control). The cows with LDA showed lower values of daily milk production, body weight and corporal condition score. The use of pH reagent strips showed to be functional in the field, when compared to a digital pH meter. Ruminant dynamics was damaged in cows affected by LDA, as it was evidenced by the higher reduction time of methylene blue. Serum values of lactate, beta-hydroxybutyrate, urea, albumin, free fatty acids and cholesterol shows to be auxiliary tools in the LDA characterization.

Robust parametric indirect estimates of the expected cost of a hospital stay with covariates and censored data.

We consider the problem of estimating the mean hospital cost of stays of a class of patients (e.g., a diagnosis-related group) as a function of patient characteristics. The statistical analysis is complicated by the asymmetry of the cost distribution, the possibility of censoring on the cost variable, and the occurrence of outliers. These problems have often been treated separately in the literature, and a method offering a joint solution to all of them is still missing. Indirect procedures have been proposed, combining an estimate of the duration distribution with an estimate of the conditional cost for a given duration. We propose a parametric version of this approach, allowing for asymmetry and censoring in the cost distribution and providing a mean cost estimator that is robust in the presence of extreme values. In addition, the new method takes covariate information into account.

Measurement of the whole body clearance of infused glycerol as a test of liver function after major hepatectomy.

Major liver resection can be used in the treatment of liver cancer. The functional capacity of liver parenchyma needs to be evaluated preoperatively because it conditions the outcome. We assessed whether the whole body clearance of glycerol, a substrate essentially metabolized in liver cells, may be suitable as a simple test of liver function. Seven patients after major hepatectomy, six patients after colectomy and 12 healthy subjects were studied. Patients were investigated on the first day after surgery. All participants were studied during a 150-min basal period followed by a 120-min infusion of 16 mumol kg-1 min-1 13C-labelled glycerol. Whole body glycerol clearance was calculated from the change in plasma glycerol concentration. Whole body glucose production was measured with 6,6 2H2 glucose infused as a tracer in the basal state and during glycerol infusion. In addition, 13C glucose synthesis was monitored to quantitate gluconeogenesis from glycerol. Patients after liver resection had higher plasma glycerol concentrations and lower whole body glycerol clearance than healthy subjects and patients after colectomy. They also had higher plasma glucagon concentrations. Their fasting glucose production was mildly elevated in the fasting state and did not change after glycerol infusion, indicating a normal hepatic autoregulation of glucose production. These results indicate that whole body glycerol clearance can be simply determined from plasma glycerol concentrations during exogenous glycerol infusion. It is significantly reduced in patients after major hepatectomy, suggesting that it constitutes a sensitive test of hepatic function. Its use as a preoperative testing procedure remains to be evaluated.

On the connectivity of the escaping set for complex exponential Misiurewicz parameters

Let $ E_{\lambda}(z)=\lambda {\rm exp}(z), \lambda\in \mathbb{C}$, be the complex exponential family. For all functions in the family there is a unique asymptotic value at 0 (and no critical values). For a fixed $ \lambda$, the set of points in $ \mathbb{C}$ with orbit tending to infinity is called the escaping set. We prove that the escaping set of $ E_{\lambda}$ with $ \lambda$ Misiurewicz (that is, a parameter for which the orbit of the singular value is strictly preperiodic) is a connected set.

Rapid Improvement and Maintenance of the Lipid Profile After Roux-en-Y Gastric Bypass (RYGBP)

Background: Dyslipidemia, a major component of the metabolic syndrome and an important cardiovascular risk factor, is one of the commonest comorbidity associated with morbid obesity. The aim of this paper is to show that RYGBP markedly improves dyslipidemia and that this improvement maintains over time. Patients and Methods: Prospectively updated databank for bariatric patients. Patients undergoing RYGBP have yearly blood tests during follow-up. The results for lipids at one to five years were compared with preoperative values. Results: The mean excess BMI loss after one and five years was 77,9 % and 72,3%respectively. After one year, there was a significant reduction of the mean total cholesterol, LDL-cholesterol, total cholesterol/HDL ratio and triglyceride values, which maintained up to five years, and an increase of the HDL fraction, which progressed until five years. The proportion of patients with abnormal values decreased from 24,3 to 6,2% for total cholesterol, from 45,1 to 11,7 %for HDL, from 53,3 to 21,9 for LDL, and from 40,5 to 10 % for triglycerides, with no significant change between three and five years, despite some weight regain. Conclusions: RYGBP rapidly improves all components of dyslipidemia, and thereby reduces the overall cardiovascular risk in operated patients.

Genesis of the Jurassic carbonate-hosted Pb-Zn deposits of Jebel Ressas (North-eastern Tunisia): Evidence from mineralogy, petrography and trace metal contents and isotope (O, C, S, Pb) geochemistry

The Jebel Ressas Pb-Zn deposits in North-Eastern Tunisia occur mainly as open-space fillings (lodes, tectonic breccia cements) in bioclastic limestones of the Upper Jurassic Ressas Formation and along the contact of this formation with Triassic rocks. The galena-sphalerite association and their alteration products (cerussite, hemimorphite, hydrozincite) are set within a calcite gangue. The Triassic rocks exhibit enrichments in trace metals, namely Pb, Co and Cd enrichment in clays and Pb, Zn, Cd, Co and Cr enrichment in carbonates, suggesting that the Triassic rocks have interacted with the ore-bearing fluids associated with the Jebel Ressas Pb-Zn deposits. The delta(18)O content of calcite associated with the Pb-Zn mineralization suggests that it is likely to have precipitated from a fluid that was in equilibrium with the Triassic dolostones. The delta(34)S values in galenas from the Pb-Zn deposits range from -1.5 to +11.4%, with an average of 5.9% and standard deviation of 3.9%. These data imply mixing of thermochemically-reduced heavy sulfur carried in geothermal- and fault-stress-driven deep-seated source fluid with bacterially-reduced light sulfur carried in topography-driven meteoric fluid. Lead isotope ratios in galenas from the Pb-Zn deposits are homogenous and indicate a single upper crustal source of base-metals for these deposits. Synthesis of the geochemical data with geological data suggests that the base-metal mineralization at Jebel Ressas was formed during the Serravallian-Tortonian (or Middle-Late Miocene) Alpine compressional tectonics.

Muscle protein waste in tumor-bearing rats is effectively antagonized by a beta 2-adrenergic agonist (clenbuterol). Role of the ATP-ubiquitin-dependent proteolytic pathway.

Tissue protein hypercatabolism (TPH) is a most important feature in cancer cachexia, particularly with regard to the skeletal muscle. The rat ascites hepatoma Yoshida AH-130 is a very suitable model system for studying the mechanisms involved in the processes that lead to tissue depletion, since it induces in the host a rapid and progressive muscle waste mainly due to TPH (Tessitore, L., G. Bonelli, and F. M. Baccino. 1987. Biochem. J. 241:153-159). Detectable plasma levels of tumor necrosis factor-alpha associated with marked perturbations in the hormonal homeostasis have been shown to concur in forcing metabolism into a catabolic setting (Tessitore, L., P. Costelli, and F. M. Baccino. 1993. Br. J. Cancer. 67:15-23). The present study was directed to investigate if beta 2-adrenergic agonists, which are known to favor skeletal muscle hypertrophy, could effectively antagonize the enhanced muscle protein breakdown in this cancer cachexia model. One such agent, i.e., clenbuterol, indeed largely prevented skeletal muscle waste in AH-130-bearing rats by restoring protein degradative rates close to control values. This normalization of protein breakdown rates was achieved through a decrease of the hyperactivation of the ATP-ubiquitin-dependent proteolytic pathway, as previously demonstrated in our laboratory (Llovera, M., C. García-Martínez, N. Agell, M. Marzábal, F. J. López-Soriano, and J. M. Argilés. 1994. FEBS (Fed. Eur. Biochem. Soc.) Lett. 338:311-318). By contrast, the drug did not exert any measurable effect on various parenchymal organs, nor did it modify the plasma level of corticosterone and insulin, which were increased and decreased, respectively, in the tumor hosts. The present data give new insights into the mechanisms by which clenbuterol exerts its preventive effect on muscle protein waste and seem to warrant the implementation of experimental protocols involving the use of clenbuterol or alike drugs in the treatment of pathological states involving TPH, particularly in skeletal muscle and heart, such as in the present model of cancer cachexia.