Connexins 43 and 26 are differentially increased after rat bladder outlet obstruction.

To evaluate the regulation of connexin expression by fluid pressure, we have studied the effects of elevated transmural urine pressure on Connexin43 (Cx43) and Cx26. We chose to focus on these two proteins out of the five connexins (Cx26, 43, 40, 37, and 45) which we found by RT-PCR to be expressed in the rat bladder, since in situ hybridization and immunofluorescence showed that Cx43 is the predominant connexin expressed by smooth muscle cells (SMC), whereas Cx26 is abundantly expressed only in the latter cell type. To evaluate whether these connexins are affected by changes in transmural urine pressure, we used a rat model of bladder outlet obstruction, in which a ligature is placed around the urethra. Under conditions of increased fluid pressure due to urine retention, we observed that the expression of both Cx43 and Cx26 increased at both transcript and protein levels, reaching a maximum 7-9 h after the ligature. Further analysis revealed that these changes were accounted for by a fourfold increase in Cx43 mRNA of SMC but not urothelial cell and by a fivefold increase in Cx26 mRNA of urothelium. Scrape-loading of propidium iodide showed that the latter change was paralleled by a twofold increase in coupling between urothelial cells. The data show that Cx43 and Cx26 are differentially regulated during bladder outlet obstruction and contribute to the response of the bladder wall to increased voiding pressure, possibly to control its elasticity.

Nuclear well logging in soils. Calibration of slim hole nuclear tools gamma-gamma and neutron-thermal neutron.

The calculation of elasticity parameters by sonic and ultra sonic wave propagation in saturated soils using Biot's theory needs the following variables : forpiation density and porosity (p, ø), compressional and shear wave velocities (Vp, Vs), fluid density, viscosity and compressibility (Pfi Ilfi Ki), matrix density and compressibility (p" K), The first four parameters can be determined in situ using logging probes. Because fluid and matrix characteristics are not modified during core extraction, they can be obtained through laboratory measurements. All parameters necessitate precise calibrations in various environments and for specific range of values encountered in soils. The slim diameter of boreholes in shallow geophysics and the high cost of petroleum equipment demand the use of specific probes, which usually only give qualitative results. The measurement 'of density is done with a gamma-gamma probe and the measurement of hydrogen index, in relation to porosity, by a neutron probe. The first step of this work has been carried out in synthetic formations in the laboratory using homogeneous media of known density and porosity. To establish borehole corrections different casings have been used. Finally a comparison between laboratory and in situ data in cored holes of known geometry and casing has been performed.

Effects of the transition time between muscle-tendon stretch and shortening on mechanical efficiency.

The net mechanical efficiency of positive work (eta(pos)) has been shown to increase if it is immediately preceded by negative work. This phenomenon is explained by the storage of elastic energy during the negative phase and its release during the subsequent positive phase. If a transition time (T) takes place, the elastic energy is dissipated into heat. The aim of the present study was to investigate the relationship between eta(pos) and T, and to determine the minimal T required so that eta(pos) reached its minimal value. Seven healthy male subjects were tested during four series of lowering-raising of the body mass. In the first series (S (0)), the negative and positive phases were executed without any transition time. In the three other series, T was varied by a timer (0.12, 0.24 and 0.56 s for series S (1), S (2) and S (3), respectively). These exercises were performed on a force platform sensitive to vertical forces to measure the mechanical work and a gas analyser was used to determine the energy expenditure. The results indicated that eta(pos) was the highest (31.1%) for the series without any transition time (S (0)). The efficiencies observed with transition times (S (1), S (2) and S (3)) were 27.7, 26.0 and 23.8%, respectively, demonstrating that T plays an important role for mechanical efficiency. The investigation of the relationship between eta(pos) and T revealed that the minimal T required so that eta(pos) reached its minimal value is 0.59 s.

Chest pulse-wave velocity: a novel approach to assess arterial stiffness.

Pulse-wave velocity (PWV) is considered as the gold-standard method to assess arterial stiffness, an independent predictor of cardiovascular morbidity and mortality. Current available devices that measure PWV need to be operated by skilled medical staff, thus, reducing the potential use of PWV in the ambulatory setting. In this paper, we present a new technique allowing continuous, unsupervised measurements of pulse transit times (PTT) in central arteries by means of a chest sensor. This technique relies on measuring the propagation time of pressure pulses from their genesis in the left ventricle to their later arrival at the cutaneous vasculature on the sternum. Combined thoracic impedance cardiography and phonocardiography are used to detect the opening of the aortic valve, from which a pre-ejection period (PEP) value is estimated. Multichannel reflective photoplethysmography at the sternum is used to detect the distal pulse-arrival time (PAT). A PTT value is then calculated as PTT = PAT - PEP. After optimizing the parameters of the chest PTT calculation algorithm on a nine-subject cohort, a prospective validation study involving 31 normo- and hypertensive subjects was performed. 1/chest PTT correlated very well with the COMPLIOR carotid to femoral PWV (r = 0.88, p < 10 (-9)). Finally, an empirical method to map chest PTT values onto chest PWV values is explored.

Chronic rejection of allogenic dermal grafts in 73 % TBSA burn patient

Rationale: Allogenic grafts are an excellent way to temporarily cover a wound. It prevents the loss of electrolytes and water, reduces the risk of infection and diminishes pain. Another advantage of the allograft is in circumventing problems such as the morbidity of skin graft donor sites. We present here the case of a patient grafted in 1991 with cultured epidermal autografts (CEA) and allogenic skin transplants on his legs, outlining the risks and potential long-term complications. Methods: The 40-year-old male patient was treated with allogenic Split Thickness Skin Graft (STSG) transplantations, CEA and Cyclosporine-A therapy. Allogenic STSG for lower extremities were harvested from a female HIV-negative organ donor. They were transplanted, de-epithelialized and subsequently covered with CEAs. Cyclosporine-A was administered systemically from the first day following transplantation until three weeks after the last CEAs were placed on the allogenic dermis. Results: Immediate results showed a 90% successful grafting under cyclosporine therapy. However, some lesions were still present 16 months later. The skin was hard with little or no elasticity. Five years after the transplantation there were no more lesions. However, a 10-year follow-up showed new ulcers on both lower extremities. All the skin of the right leg was removed and replaced by STSG from the patient's back. Postoperative results were excellent with a 100% graft take. The anatomopathology showed dermo-hypodermic tissue with fibrosis of the dermis, vasculopathy and chronic ulcers compatible with chronic rejection. Conclusion: While early functional results of the allografts may seem encouraging, their long-term evolution remains uncertain and, in this case, presents complications. The apparent antigenic effect of the dermal tissue may be controlled with long-term immunosuppression which may cause important secondary effects. Even with such treatments, 15 years after organ transplantation, about 35% of a transplant is no longer functional. It is therefore important to take these long-term observations into consideration when treating sensitive areas such as hands or a face.

Measurements of seismic attenuation and transient fluid pressure in partially saturated Berea sandstone: Evidence of fluid flow on the mesoscopic scale

A novel laboratory technique is proposed to investigate wave-induced fluid flow on the mesoscopic scale as a mechanism for seismic attenuation in partially saturated rocks. This technique combines measurements of seismic attenuation in the frequency range from 1 to 100?Hz with measurements of transient fluid pressure as a response of a step stress applied on top of the sample. We used a Berea sandstone sample partially saturated with water. The laboratory results suggest that wave-induced fluid flow on the mesoscopic scale is dominant in partially saturated samples. A 3-D numerical model representing the sample was used to verify the experimental results. Biot's equations of consolidation were solved with the finite-element method. Wave-induced fluid flow on the mesoscopic scale was the only attenuation mechanism accounted for in the numerical solution. The numerically calculated transient fluid pressure reproduced the laboratory data. Moreover, the numerically calculated attenuation, superposed to the frequency-independent matrix anelasticity, reproduced the attenuation measured in the laboratory in the partially saturated sample. This experimental?numerical fit demonstrates that wave-induced fluid flow on the mesoscopic scale and matrix anelasticity are the dominant mechanisms for seismic attenuation in partially saturated Berea sandstone.

New formulation of vasoactive intestinal peptide using liposomes in hyaluronic acid gel for uveitis.

We evaluated the benefits of a novel formulation of vasoactive intestinal peptide (VIP) based on the incorporation of VIP-loaded rhodamine-conjugated liposomes (VIP-Rh-Lip) within hyaluronic acid (HA) gel (Gel-VIP-Rh-Lip) for the treatment of endotoxin-induced uveitis (EIU) in comparison with VIP-Rh-Lip alone. In vitro release study and rheological analysis showed that interactions between HA chains and liposomes resulted in increased viscosity and reinforced elasticity of the gel. In vivo a single intravitreal injection of Gel-VIP-Rh-Lip was performed in rats 7 days prior to uveitis induction by subcutaneous lipopolysaccharide injection. The maximal ocular inflammation occurs within 16-24 h in controls (VIP-Rh-Lip, unloaded-Rh-Lip). Whereas intraocular injection of VIP-Rh-Lip had no effect on EIU severity compared with controls, Gel-VIP-Rh-Lip reduced significantly the clinical score and number of inflammatory cells infiltrating the eye. The fate of liposomes, VIP and HA in the eyes, regional and inguinal lymph nodes and spleen was analyzed by immunostaining and fluorescence microscopy. Retention of liposomes by HA gel was observed in vitro and in vivo. Inflammation severity seemed to impact on system stability resulting in the delayed release of VIP. Thus, HA gel containing VIP-Rh-Lip is an efficient strategy to obtain a sustained delivery of VIP in ocular and lymph node tissues.

Hepatic amyloidosis increases liver stiffness measured by transient elastography.

Liver stiffness values in transient elastography (TE) have to be interpreted with caution. Steatosis, congestion, acute inflammation and extrahepatic cholestasis can indeed influence measurements. Obtained stiffness values in the cirrhotic range can also be present in the absence of fibrosis as in hepatic amyloidosis. Here we report two cases of systemic amyloidosis with hepatic involvement where high stiffness values were measured at TE. In fact, deposits of amyloid may increase the rigidity of the liver parenchyma resulting in higher liver stiffness values. Therefore, results of TE should always be interpreted in their clinical context and if inconsistent, the performance of a liver biopsy might be necessary.

Looking for orders of magnitude : five essays in trade and the environment and economic geography

General Summary Although the chapters of this thesis address a variety of issues, the principal aim is common: test economic ideas in an international economic context. The intention has been to supply empirical findings using the largest suitable data sets and making use of the most appropriate empirical techniques. This thesis can roughly be divided into two parts: the first one, corresponding to the first two chapters, investigates the link between trade and the environment, the second one, the last three chapters, is related to economic geography issues. Environmental problems are omnipresent in the daily press nowadays and one of the arguments put forward is that globalisation causes severe environmental problems through the reallocation of investments and production to countries with less stringent environmental regulations. A measure of the amplitude of this undesirable effect is provided in the first part. The third and the fourth chapters explore the productivity effects of agglomeration. The computed spillover effects between different sectors indicate how cluster-formation might be productivity enhancing. The last chapter is not about how to better understand the world but how to measure it and it was just a great pleasure to work on it. "The Economist" writes every week about the impressive population and economic growth observed in China and India, and everybody agrees that the world's center of gravity has shifted. But by how much and how fast did it shift? An answer is given in the last part, which proposes a global measure for the location of world production and allows to visualize our results in Google Earth. A short summary of each of the five chapters is provided below. The first chapter, entitled "Unraveling the World-Wide Pollution-Haven Effect" investigates the relative strength of the pollution haven effect (PH, comparative advantage in dirty products due to differences in environmental regulation) and the factor endowment effect (FE, comparative advantage in dirty, capital intensive products due to differences in endowments). We compute the pollution content of imports using the IPPS coefficients (for three pollutants, namely biological oxygen demand, sulphur dioxide and toxic pollution intensity for all manufacturing sectors) provided by the World Bank and use a gravity-type framework to isolate the two above mentioned effects. Our study covers 48 countries that can be classified into 29 Southern and 19 Northern countries and uses the lead content of gasoline as proxy for environmental stringency. For North-South trade we find significant PH and FE effects going in the expected, opposite directions and being of similar magnitude. However, when looking at world trade, the effects become very small because of the high North-North trade share, where we have no a priori expectations about the signs of these effects. Therefore popular fears about the trade effects of differences in environmental regulations might by exaggerated. The second chapter is entitled "Is trade bad for the Environment? Decomposing worldwide SO2 emissions, 1990-2000". First we construct a novel and large database containing reasonable estimates of SO2 emission intensities per unit labor that vary across countries, periods and manufacturing sectors. Then we use these original data (covering 31 developed and 31 developing countries) to decompose the worldwide SO2 emissions into the three well known dynamic effects (scale, technique and composition effect). We find that the positive scale (+9,5%) and the negative technique (-12.5%) effect are the main driving forces of emission changes. Composition effects between countries and sectors are smaller, both negative and of similar magnitude (-3.5% each). Given that trade matters via the composition effects this means that trade reduces total emissions. We next construct, in a first experiment, a hypothetical world where no trade happens, i.e. each country produces its imports at home and does no longer produce its exports. The difference between the actual and this no-trade world allows us (under the omission of price effects) to compute a static first-order trade effect. The latter now increases total world emissions because it allows, on average, dirty countries to specialize in dirty products. However, this effect is smaller (3.5%) in 2000 than in 1990 (10%), in line with the negative dynamic composition effect identified in the previous exercise. We then propose a second experiment, comparing effective emissions with the maximum or minimum possible level of SO2 emissions. These hypothetical levels of emissions are obtained by reallocating labour accordingly across sectors within each country (under the country-employment and the world industry-production constraints). Using linear programming techniques, we show that emissions are reduced by 90% with respect to the worst case, but that they could still be reduced further by another 80% if emissions were to be minimized. The findings from this chapter go together with those from chapter one in the sense that trade-induced composition effect do not seem to be the main source of pollution, at least in the recent past. Going now to the economic geography part of this thesis, the third chapter, entitled "A Dynamic Model with Sectoral Agglomeration Effects" consists of a short note that derives the theoretical model estimated in the fourth chapter. The derivation is directly based on the multi-regional framework by Ciccone (2002) but extends it in order to include sectoral disaggregation and a temporal dimension. This allows us formally to write present productivity as a function of past productivity and other contemporaneous and past control variables. The fourth chapter entitled "Sectoral Agglomeration Effects in a Panel of European Regions" takes the final equation derived in chapter three to the data. We investigate the empirical link between density and labour productivity based on regional data (245 NUTS-2 regions over the period 1980-2003). Using dynamic panel techniques allows us to control for the possible endogeneity of density and for region specific effects. We find a positive long run elasticity of density with respect to labour productivity of about 13%. When using data at the sectoral level it seems that positive cross-sector and negative own-sector externalities are present in manufacturing while financial services display strong positive own-sector effects. The fifth and last chapter entitled "Is the World's Economic Center of Gravity Already in Asia?" computes the world economic, demographic and geographic center of gravity for 1975-2004 and compares them. Based on data for the largest cities in the world and using the physical concept of center of mass, we find that the world's economic center of gravity is still located in Europe, even though there is a clear shift towards Asia. To sum up, this thesis makes three main contributions. First, it provides new estimates of orders of magnitudes for the role of trade in the globalisation and environment debate. Second, it computes reliable and disaggregated elasticities for the effect of density on labour productivity in European regions. Third, it allows us, in a geometrically rigorous way, to track the path of the world's economic center of gravity.

Frequency-dependent attenuation as a potential indicator of oil saturation

At seismic frequencies, wave-induced fluid flow is a major cause of P-wave attenuation in partially saturated porous rocks. Attenuation is of great importance for the oil industry in the interpretation of seismic field data. Here, the effects on P-wave attenuation resulting from changes in oil saturation are studied for media with coexisting water, oil, and gas. For that, creep experiments are numerically simulated by solving Biot's equations for consolidation of poroelastic media with the finite-element method. The experiments yield time-dependent stress?strain relations that are used to calculate the complex P-wave modulus from which frequency-dependent P-wave attenuation is determined. The models are layered media with periodically alternating triplets of layers. Models consisting of triplets of layers having randomly varying layer thicknesses are also considered. The layers in each triplet are fully saturated with water, oil, and gas. The layer saturated with water has lower porosity and permeability than the layers saturated with oil and gas. These models represent hydrocarbon reservoirs in which water is the wetting fluid preferentially saturating regions of lower porosity. The results from the numerical experiments showed that increasing oil saturation, connected to a decrease in gas saturation, resulted in a significant increase of attenuation at low frequencies (lower than 2 Hz). Furthermore, replacing the oil with water resulted in a distinguishable behavior of the frequency-dependent attenuation. These results imply that, according to the physical mechanism of wave-induced fluid flow, frequency-dependent attenuation in media saturated with water, oil, and gas is a potential indicator of oil saturation.

High-density collagen gel tubes as a matrix for primary human bladder smooth muscle cells.

Tissue-engineered grafts for the urinary tract are being investigated for the potential treatment of several urologic diseases. These grafts, predominantly tubular-shaped, usually require in vitro culture prior to implantation to allow cell engraftment on initially cell-free scaffolds. We have developed a method to produce tubular-shaped collagen scaffolds based on plastic compression. Our approach produces a ready cell-seeded graft that does not need further in vitro culture prior to implantation. The tubular collagen scaffolds were in particular investigated for their structural, mechanical and biological properties. The resulting construct showed an especially high collagen density, and was characterized by favorable mechanical properties assessed by axial extension and radial dilation. Young modulus in particular was greater than non-compressed collagen tubes. Seeding densities affected proliferation rate of primary human bladder smooth muscle cells. An optimal seeding density of 10(6) cells per construct resulted in a 25-fold increase in Alamar blue-based fluorescence after 2 wk in culture. These high-density collagen gel tubes, ready seeded with smooth muscle cells could be further seeded with urothelial cells, drastically shortening the production time of graft for urinary tract regeneration.

Osteoporotic fracture risk in elderly women: estimation with quantitative heel US and clinical risk factors

PURPOSE: To derive a prediction rule by using prospectively obtained clinical and bone ultrasonographic (US) data to identify elderly women at risk for osteoporotic fractures. MATERIALS AND METHODS: The study was approved by the Swiss Ethics Committee. A prediction rule was computed by using data from a 3-year prospective multicenter study to assess the predictive value of heel-bone quantitative US in 6174 Swiss women aged 70-85 years. A quantitative US device to calculate the stiffness index at the heel was used. Baseline characteristics, known risk factors for osteoporosis and fall, and the quantitative US stiffness index were used to elaborate a predictive rule for osteoporotic fracture. Predictive values were determined by using a univariate Cox model and were adjusted with multivariate analysis. RESULTS: There were five risk factors for the incidence of osteoporotic fracture: older age (>75 years) (P < .001), low heel quantitative US stiffness index (<78%) (P < .001), history of fracture (P = .001), recent fall (P = .001), and a failed chair test (P = .029). The score points assigned to these risk factors were as follows: age, 2 (3 if age > 80 years); low quantitative US stiffness index, 5 (7.5 if stiffness index < 60%); history of fracture, 1; recent fall, 1.5; and failed chair test, 1. The cutoff value to obtain a high sensitivity (90%) was 4.5. With this cutoff, 1464 women were at lower risk (score, <4.5) and 4710 were at higher risk (score, >or=4.5) for fracture. Among the higher-risk women, 6.1% had an osteoporotic fracture, versus 1.8% of women at lower risk. Among the women who had a hip fracture, 90% were in the higher-risk group. CONCLUSION: A prediction rule obtained by using quantitative US stiffness index and four clinical risk factors helped discriminate, with high sensitivity, women at higher versus those at lower risk for osteoporotic fracture.

Constraints on the permeability structure of alluvial aquifers from the poro-elastic inversion of multi-frequency P-wave velocity logs

We have explored the possibility of obtaining first-order permeability estimates for saturated alluvial sediments based on the poro-elastic interpretation of the P-wave velocity dispersion inferred from sonic logs. Modern sonic logging tools designed for environmental and engineering applications allow one for P-wave velocity measurements at multiple emitter frequencies over a bandwidth covering 5 to 10 octaves. Methodological considerations indicate that, for saturated unconsolidated sediments in the silt to sand range and typical emitter frequencies ranging from approximately 1 to 30 kHz, the observable velocity dispersion should be sufficiently pronounced to allow one for reliable first-order estimations of the permeability structure. The corresponding predictions have been tested on and verified for a borehole penetrating a typical surficial alluvial aquifer. In addition to multifrequency sonic logs, a comprehensive suite of nuclear and electrical logs, an S-wave log, a litholog, and a limited number laboratory measurements of the permeability from retrieved core material were also available. This complementary information was found to be essential for parameterizing the poro-elastic inversion procedure and for assessing the uncertainty and internal consistency of corresponding permeability estimates. Our results indicate that the thus obtained permeability estimates are largely consistent with those expected based on the corresponding granulometric characteristics, as well as with the available evidence form laboratory measurements. These findings are also consistent with evidence from ocean acoustics, which indicate that, over a frequency range of several orders-of-magnitude, the classical theory of poro-elasticity is generally capable of explaining the observed P-wave velocity dispersion in medium- to fine-grained seabed sediments

Conduit artery compliance and distensibility are not necessarily reduced in hypertension.

The goal of this study was to investigate whether the elastic behavior of conduit arteries of humans or rats is altered as a result of concomitant hypertension. Forearm arterial cross-sectional compliance-pressure curves were determined noninvasively by means of a high precision ultrasonic echo-tracking device coupled to a photoplethysmograph (Finapres system) allowing simultaneous arterial diameter and finger blood pressure monitoring. Seventeen newly diagnosed hypertensive patients with a humeral blood pressure of 163/103 +/- 4.4/2.2 mm Hg (mean +/- SEM) and 17 age- and sex-matched normotensive controls with a humeral blood pressure of 121/77 +/- 3.2/1.9 mm Hg were included in the study. Compliance-pressure curves were also established at the carotid artery of 16-week-old anesthetized spontaneously hypertensive rats (n = 14) as well as Wistar-Kyoto normotensive animals (n = 15) using the same echo-tracking device. In these animals, intra-arterial pressure was monitored in the contralateral carotid artery. Mean blood pressures averaged 197 +/- 4 and 140 +/- 3 mm Hg in the hypertensive and normotensive rats, respectively. Despite the considerable differences in blood pressure, the diameter-pressure and cross-sectional compliance-pressure and distensibility-pressure curves were not different when hypertensive patients or animals were compared with their respective controls. These results suggest that the elastic behavior of a medium size muscular artery (radial) in humans and of an elastic artery (carotid) in rats is not necessarily altered by an increase in blood pressure.

A role for septins in the interaction between the Listeria monocytogenes INVASION PROTEIN InlB and the Met receptor.

Septins are conserved GTPases that form filaments and are required for cell division. During interphase, septin filaments associate with cellular membrane and cytoskeleton networks, yet the functional significance of these associations have, to our knowledge, remained unknown. We recently discovered that different septins, SEPT2 and SEPT11, regulate the InlB-mediated entry of Listeria monocytogenes into host cells. Here we address the role of SEPT2 and SEPT11 in the InlB-Met interactions underlying Listeria invasion to explore how septins modulate surface receptor function. We observed that differences in InlB-mediated Listeria entry correlated with differences in Met surface expression caused by septin depletion. Using atomic force microscopy on living cells, we show that septin depletion significantly reduced the unbinding force of InlB-Met interaction and the viscosity of membrane tethers at locations where the InlB-Met interaction occurs. Strikingly, the same order of difference was observed for cells in which the actin cytoskeleton was disrupted. Consistent with a proposed role of septins in association with the actin cytoskeleton, we show that cell elasticity is decreased upon septin or actin inactivation. Septins are therefore likely to participate in anchorage of the Met receptor to the actin cytoskeleton, and represent a critical determinant in surface receptor function.