Elevated albumin in retinas of monkeys with experimental glaucoma.

PURPOSE: To establish the identity of a prominent protein, approximately 70 kDa, that is markedly increased in the retina of monkeys with experimental glaucoma compared with the fellow control retina, the relationship to glaucoma severity, and its localization in the retina. METHODS: Retinal extracts were subjected to 2-D gel electrophoresis to identify differentially expressed proteins. Purified peptides from the abundant 70 kDa protein were analyzed and identified by liquid chromatography/mass spectrometry/mass spectrometry (LC/MS/MS) separation, and collision-induced dissociation sequencing. Protein identity was performed on MASCOT (Matrix Science, Boston, MA) and confirmed by Western blot. The relationship between the increase in this protein and glaucoma severity was investigated by regression analyses. Protein localization in retina was evaluated by immunohistochemistry with confocal imaging. RESULTS: The abundant protein was identified as Macaca mulatta serum albumin precursor (67 kDa) from eight non-overlapping proteolytic fragments, and the identity was confirmed by Western blot. The average increase in retinal albumin content was 2.3 fold (P = 0.015). In glaucoma eyes, albumin was localized to some neurons of the inner nuclear layer, in the inner plexiform layer, and along the vitreal surface, but it was only found in blood vessels in control retinas. CONCLUSIONS: Albumin is the abundant protein found in the glaucomatous monkey retinas. The increased albumin is primarily localized to the inner retina where oxidative damage associated with experimental glaucoma is known to be prominent. Since albumin is a major antioxidant, the increase of albumin in the retinas of eyes with experimental glaucoma may serve to protect the retina against oxidative damage.

End-tidal CO2 pressure: an important parameter for a correct interpretation of changes in cerebral hemodynamics and oxygenation measured with functional near infrared spectrophotometry (fNIRS)

The aim of the present study was to investigate the effects of different speech tasks (recitation of prose (PR), alliteration (AR) and hexameter (HR) verses) and a control task (mental arithmetic (MA) with voicing of the result) on endtidal CO2 (ET-CO2), cerebral hemodynamics; i.e. total hemoglobin (tHb) and tissue oxygen saturation (StO2). tHb and StO2 were measured with a frequency domain near infrared spectrophotometer (ISS Inc., USA) and ET-CO2 with a gas analyzer (Nellcor N1000). Measurements were performed in 24 adult volunteers (11 female, 13 male; age range 22 to 64 years) during task performance in a randomized order on 4 different days to avoid potential carry over effects. Statistical analysis was applied to test differences between baseline, 2 recitation and 5 recovery periods. The two brain hemispheres and 4 tasks were tested separately. Data analysis revealed that during the recitation tasks (PR, AR and HR) StO2 decreased statistically significant (p < 0.05) during PR and AR in the right prefrontal cortex (PFC) and during AR and HR in the left PFC. tHb showed a significant decrease during HR in the right PFC and during PR, AR and HR in the left PFC. During the MA task, StO2 increased significantly. A significant decrease in ET-CO2 was found during all 4 tasks with the smallest decrease during the MA task. In conclusion, we hypothesize that the observed changes in tHb and StO2 are mainly caused by an altered breathing during the tasks that led a lowering of the CO2 content in the blood provoked a cerebral CO2 reaction, i.e. a vasoconstriction of blood vessels due to decreased CO2 pressure and thereby decrease in cerebral blood volume. Therefore, breathing changes should be monitored during brain studies involving speech when using functional near infrared spectroscopy (fNIRS) to ensure a correct interpretation of changes in hemodynamics and oxygenation.

Heritability of ambulatory and office blood pressure in the Swiss population

BACKGROUND Blood pressure (BP) is known to aggregate in families. Yet, heritability estimates are population-specific and no Swiss data have been published so far. We estimated the heritability of ambulatory and office BP in a Swiss population-based sample. METHODS The Swiss Kidney Project on Genes in Hypertension is a population-based family study focusing on BP genetics. Office and ambulatory BP were measured in 1009 individuals from 271 nuclear families. Heritability was estimated for SBP, DBP, and pulse pressure using a maximum likelihood method implanted in the Statistical Analysis in Genetic Epidemiology software. RESULTS The 518 women and 491 men included in this analysis had a mean (±SD) age of 48.3 (±17.4) and 47.3 (±17.7) years, and a mean BMI of 23.8 (±4.2) and 25.9 (±4.1) kg/m, respectively. Narrow-sense heritability estimates (±standard error) for ambulatory SBP, DBP, and pulse pressure were 0.37 ± 0.07, 0.26 ± 0.07, and 0.29 ± 0.07 for 24-h BP; 0.39 ± 0.07, 0.28 ± 0.07, and 0.27 ± 0.07 for day BP; and 0.25 ± 0.07, 0.20 ± 0.07, and 0.30 ± 0.07 for night BP, respectively (all P < 0.001). Heritability estimates for office SBP, DBP, and pulse pressure were 0.21 ± 0.08, 0.25 ± 0.08, and 0.18 ± 0.07 (all P < 0.01). CONCLUSIONS We found significant heritability estimates for both ambulatory and office BP in this Swiss population-based study. Our findings justify the ongoing search for the genetic determinants of BP.

Attenuated portal hypertension in germ-free mice: Function of bacterial flora on the development of mesenteric lymphatic and blood vessels

Intestinal bacterial flora may induce splanchnic hemodynamic and histological alterations that are associated with portal hypertension (PH). We hypothesized that experimental PH would be attenuated in the complete absence of intestinal bacteria. We induced prehepatic PH by partial portal vein ligation (PPVL) in germ-free (GF) or mice colonized with altered Schaedler's flora (ASF). After 2 or 7 days, we performed hemodynamic measurements, including portal pressure (PP) and portosystemic shunts (PSS), and collected tissues for histomorphology, microbiology, and gene expression studies. Mice colonized with intestinal microbiota presented significantly higher PP levels after PPVL, compared to GF, mice. Presence of bacterial flora was also associated with significantly increased PSS and spleen weight. However, there were no hemodynamic differences between sham-operated mice in the presence or absence of intestinal flora. Bacterial translocation to the spleen was demonstrated 2 days, but not 7 days, after PPVL. Intestinal lymphatic and blood vessels were more abundant in colonized and in portal hypertensive mice, as compared to GF and sham-operated mice. Expression of the intestinal antimicrobial peptide, angiogenin-4, was suppressed in GF mice, but increased significantly after PPVL, whereas other angiogenic factors remained unchanged. Moreover, colonization of GF mice with ASF 2 days after PPVL led to a significant increase in intestinal blood vessels, compared to controls. The relative increase in PP after PPVL in ASF and specific pathogen-free mice was not significantly different. CONCLUSION In the complete absence of gut microbial flora PP is normal, but experimental PH is significantly attenuated. Intestinal mucosal lymphatic and blood vessels induced by bacterial colonization may contribute to development of PH.

Accident Management Actions In An Upper-Head Small-Break Loss-Of-Coolant Accident With High-Pressure Safety Injection Failed

Since the Three Mile Island accident, an important focus of pressurized water reactor (PWR) transient analyses has been a small-break loss-of-coolant accident (SBLOCA). In 2002, the discovery of thinning of the vessel head wall at the Davis Besse nuclear power plant reactor indicated the possibility of an SBLOCA in the upper head of the reactor vessel as a result of circumferential cracking of a control rod drive mechanism penetration nozzle - which has cast even greater importance on the study of SBLOCAs. Several experimental tests have been performed at the Large Scale Test Facility to simulate the behavior of a PWR during an upper-head SBLOCA. The last of these tests, Organisation for Economic Co-operation and Development Nuclear Energy Agency Rig of Safety Assessment (OECD/NEA ROSA) Test 6.1, was performed in 2005. This test was simulated with the TRACE 5.0 code, and good agreement with the experimental results was obtained. Additionally, a broad analysis of an upper-head SBLOCA with high-pressure safety injection failed in a Westinghouse PWR was performed taking into account different accident management actions and conditions in order to check their suitability. This issue has been analyzed also in the framework of the OECD/NEA ROSA project and the Code Applications and Maintenance Program (CAMP). The main conclusion is that the current emergency operating procedures for Westinghouse reactor design are adequate for these kinds of sequences, and they do not need to be modified.

In situ surveillance of capacitive pressure transmitter dynamic poles

In this work, a methodology is proposed to find the dynamic poles of a capacitive pressure transmitter in order to enhance and extend the online surveillance of this type of sensor based on the response time measurement by applying noise analysis techniques and the dynamic data system procedure. Several measurements taken from a pressurized water reactor have been analyzed. The methodology proposes an autoregressive fit whose order is determined by the sensor dynamic poles. Nevertheless, the signals that have been analyzed could not be filtered properly in order to remove the plant noise; thus, this was considered as an additional pair of complex conjugate poles. With this methodology we have come up with the numerical value of the sensor second real pole in spite of its low influence on the sensor dynamic response. This opens up a more accurate online sensor surveillance since the previous methods were achieved by considering one real pole only.

Pressure-mediated oligonucleotide transfection of rat and human cardiovascular tissues

The application of gene therapy to human disease is currently restricted by the relatively low efficiency and potential hazards of methods of oligonucleotide or gene delivery. Antisense or transcription factor decoy oligonucleotides have been shown to be effective at altering gene expression in cell culture expreriments, but their in vivo application is limited by the efficiency of cellular delivery, the intracellular stability of the compounds, and their duration of activity. We report herein the development of a highly efficient method for naked oligodeoxynucleotide (ODN) transfection into cardiovascular tissues by using controlled, nondistending pressure without the use of viral vectors, lipid formulations, or exposure to other adjunctive, potentially hazardous substances. In this study, we have documented the ability of ex vivo, pressure-mediated transfection to achieve nuclear localization of fluorescent (FITC)-labeled ODN in approximately 90% and 50% of cells in intact human saphenous vein and rat myocardium, respectively. We have further documented that pressure-mediated delivery of antisense ODN can functionally inhibit target gene expression in both of these tissues in a sequence-specific manner at the mRNA and protein levels. This oligonucleotide transfection system may represent a safe means of achieving the intraoperative genetic engineering of failure-resistant human bypass grafts and may provide an avenue for the genetic manipultation of cardiac allograft rejection, allograft vasculopathy, or other transplant diseases.

Cardiovascular abnormalities with normal blood pressure in tissue kallikrein-deficient mice

Tissue kallikrein is a serine protease thought to be involved in the generation of bioactive peptide kinins in many organs like the kidneys, colon, salivary glands, pancreas, and blood vessels. Low renal synthesis and urinary excretion of tissue kallikrein have been repeatedly linked to hypertension in animals and humans, but the exact role of the protease in cardiovascular function has not been established largely because of the lack of specific inhibitors. This study demonstrates that mice lacking tissue kallikrein are unable to generate significant levels of kinins in most tissues and develop cardiovascular abnormalities early in adulthood despite normal blood pressure. The heart exhibits septum and posterior wall thinning and a tendency to dilatation resulting in reduced left ventricular mass. Cardiac function estimated in vivo and in vitro is decreased both under basal conditions and in response to βadrenergic stimulation. Furthermore, flow-induced vasodilatation is impaired in isolated perfused carotid arteries, which express, like the heart, low levels of the protease. These data show that tissue kallikrein is the main kinin-generating enzyme in vivo and that a functional kallikrein–kinin system is necessary for normal cardiac and arterial function in the mouse. They suggest that the kallikrein–kinin system could be involved in the development or progression of cardiovascular diseases.

Forerunners or scaremongers? Germany to abandon nuclear power. OSW Commentary No. 58, 2011-07-21

The German government’s final decision to abandon nuclear power as of 2022 has been expected for months. However, instead of calming the waters, providing solutions and answering the question ‘What next?’, it has only fanned the flames. Even the adoption of legal amendments enforcing the government’s decision by the German parliament (both the Bundestag and the Bundesrat) in late June and early July has not calmed the situation. It is more than apparent that these decisions have been made under emotional pressure: there was not enough time for accurate calculations to be made and consideration to be given to the consequences of Germany abandoning nuclear power. Chancellor Angela Merkel has so far been unable to fully convince the public that the ‘energy shift is a huge opportunity’ and that this process will be carried out on condition that ‘the supplies remain secure, the climate protected and the whole process economically efficient’1. German economic associations have warned against a politically motivated, ill-judged and irreversible abandonment of nuclear energy. They are anxious about an increase in electricity prices, the instability of supplies and environmental damage. The government believes, however, that green technologies will become a new driving force for the German economy and its main export commodity. Before that happens the industry will have to increase its use of electricity produced from fossil fuels, mainly natural gas imported from Russia. This may be exploited by Gazprom which will try to strengthen its position on the German market, and thus in the entire EU.

The nuclear safety framework in the European Union after Fukushima. Egmont Paper No. 73, December 2014

Summary. On 11 March 2011, a devastating earthquake struck Japan and caused a major nuclear accident at the Fukushima Daiichi nuclear plant. The disaster confirmed that nuclear reactors must be protected even against accidents that have been assessed as highly unlikely. It also revealed a well-known catalogue of problems: faulty design, insufficient back-up systems, human error, inadequate contingency plans, and poor communications. The catastrophe triggered the rapid launch of a major re-examination of nuclear reactor security in Europe. It also stopped in its tracks what had appeared to be a ‘nuclear renaissance’, both in Europe and globally, especially in the emerging countries. Under the accumulated pressure of rising demand and climate warming, many new nuclear projects had been proposed. Since 2011 there has been more ambivalence, especially in Europe. Some Member States have even decided to abandon the nuclear sector altogether. This Egmont Paper aims to examine the reactions of the EU regarding nuclear safety since 2011. Firstly, a general description of the nuclear sector in Europe is provided. The nuclear production of electricity currently employs around 500,000 people, including those working in the supply chain. It generates approximately €70 billion per year. It provides roughly 30% of the electricity consumed in the EU. At the end of 2013, there were 131 nuclear power reactors active in the EU, located in 14 countries. Four new reactors are under construction in France, Slovakia and Finland. Secondly, this paper will present the Euratom legal framework regarding nuclear safety. The European Atomic Energy Community (EAEC or Euratom) Treaty was signed in 1957, and somewhat obscured by the European Economic Community (EEC) Treaty. It was a more classical treaty, establishing institutions with limited powers. Its development remained relatively modest until the Chernobyl catastrophe, which provoked many initiatives. The most important was the final adoption of the Nuclear Safety Directive 2009/71. Thirdly, the general symbiosis between Euratom and the International Atomic Energy Agency (IAEA) will be explained. Fourthly, the paper analyses the initiatives taken by the EU in the wake of the Fukushima catastrophe. These initiatives are centred around the famous ‘stress tests’. Fifthly, the most important legal change brought about by this event was the revision of Directive 2009/71. Directive 2014/87 has been adopted quite rapidly, and has deepened in various ways the role of the EU in nuclear safety. It has reinforced the role and effective independence of the national regulatory authorities. It has enhanced transparency on nuclear safety matters. It has strengthened principles, and introduced new general nuclear safety objectives and requirements, addressing specific technical issues across the entire life cycle of nuclear installations, and in particular, nuclear power plants. It has extended monitoring and the exchange of experiences by establishing a European system of peer reviews. Finally, it has established a mechanism for developing EU-wide harmonized nuclear safety guidelines. In spite of these various improvements, Directive 2014/87 Euratom still reflects the ambiguity of the Euratom system in general, and especially in the field of nuclear safety. The use of nuclear energy remains controversial among Member States. Some of them remain adamantly in favour, others against or ambivalent. The intervention of the EAEC institutions remains sensitive. The use of the traditional Community method remains limited. The peer review method remains a very peculiar mechanism that deserves more attention.

The consequences for Russia of the nuclear deal with Iran. OSW COMMENTARY NUMBER 177/03.08.2015

The five permanent members of the UN Security Council (the USA, the United Kingdom, China, France and Russia) plus Germany and the European Union signed a deal with Iran on 14 July in Vienna (a Plan of Action with five appendices, henceforth referred to as the Vienna Agreement). Under this agreement, Iran undertook to restrict its nuclear programme and to bring it under international scrutiny for 15 years in exchange for a gradual lifting of international sanctions (both those imposed between 2006 and 2010 by the UN Security Council and the unilateral US and EU sanctions). Even though Russia has officially reacted positively to this deal, the consequences it will have are rather ambiguous from Moscow’s point of view. Iran looks set to become stronger and will possibly normalise its relations with the West, and especially the United States. This, in political terms, is a disadvantage for Russia. The Kremlin’s ability to use its policy towards Iran as a bargaining chip in contacts with Washington will be reduced significantly. In turn, the benefits will include improving the perception of Russia in the West and the opening up of new opportunities for the geopolitical game in the region, both with Iran and its opponents in the Arab world. Similarly, in economic terms, the possible lifting of sanctions will offer Russia new opportunities to achieve immediate benefits owing to co-operation in the nuclear and military-technical areas. In the short term, the lifting of sanctions will not pose any threat to Russia’s position on the global energy markets. However, in the long term, the end of Iran’s international isolation may bring negative consequences for Russia, such as the dominant position of Western and/or Chinese companies in the Iranian upstream sector, rising exports of Iranian oil and gas to EU and Asian markets (which are essential for Russia) and the downward pressure on oil and gas prices.

Process development for making SM-1 instrumented fuel plates by gas-pressure bonding /

"Contract No. W-7405-eng-92."

Water characteristics in cooked beef as influenced by ageing and high-pressure treatment -an NMR micro imaging study

The water characteristics in cooked pressure-heat treated (45 degreesC for 45 min prior to pressurisation at 150 MPa for 30 min) and non-pressurised, cooked (control) samples of beef Longissimus aged for 1, 3, 8 or 16 days were studied by nuclear magnetic resonance microscopy. A multi-echo sequence was used to obtain T2 images, and independent of ageing period, the T2 values were found to be lower in pressure-heat treated meat revealing alterations in water characteristics of pressure-treated, cooked meat compared with cooked meat. With increasing ageing duration, the T2 values in both pressure-treated, cooked and cooked meat decreased indicating that the water became more tightly trapped in the protein network. In addition, independent of length of ageing period the relationship between cooking loss in the cooked meat and transverse relaxation differed between non-pressurised and pressure-treated meat. which reveals that the mechanisms changing the water properties in beef during ageing are different from those occuring during pressure-heat treatment of meat. (C) 2003 Elsevier Ltd. All rights reserved.

Pressure and temperature effects on metal-to-metal charge transfer in cyano-bridged Co-III-Fe-II complexes

The effects of pressure and temperature on the energy (E-op) of the metal-to-metal charge transfer (MMCT, Fe-II --> Co-III) transition of the cyano-bridged complexes trans - [(LCoNCFe)-Co-14(CN)(5)](-) and cis-[(LCoNCFe)-Co-14(CN)(5)](-) (where L-14 = 6-methyl-1,4,8,11-tetraazacyclotetradecan-6-amine) were examined. The changes in the redox potentials of the cobalt and iron metal centres with pressure and temperature were also examined and the results interpreted with Marcus Hush theory. The observed redox reaction volumes can mainly be accounted for in terms of localised electrostriction effects. The shifts in E-op due to both pressure and temperature were found to be less than the shifts in the energy difference (E degrees) between the Co-III-Fe-II and Co-II-Fe-III redox isomers. The pressure and temperature dependence of the reorganisational energy, as well as contributions arising from the different spin states of Co-II, are discussed in order to account for this trend. To study the effect of pressure on Co-III electronic absorption bands, a new cyano-bridged complex, trans - [(LCoNCCo)-Co-14(CN)(5)], was prepared and characterised spectroscopically and structurally. X-Ray crystallography revealed this complex to be isostructural with trans -[(LCoNCFe)-Co-14(CN)(5)] center dot 5H(2)O.

Equilibrium swelling measurements of network and semicrystalline polymers in supercritical carbon dioxide using high-pressure NMR

The extent of swelling of cross-linked poly(dimethylsiloxane) and linear low-density poly(ethylene) in supercritical CO2 has been investigated using high-pressure NMR spectroscopy and microscopy. Poly(dimethylsiloxane) was cross-linked to four different cross-link densities and swollen in supercritical CO2. The Flory-Huggins interaction parameter, x, was found to be 0.62 at 300 bar and 45 degrees C, indicating that supercritical CO2 is a relatively poor solvent compared to toluene or benzene. Linear low-density poly(ethylene) was shown to exhibit negligible swelling upon exposure to supercritical CO2 up to 300 bar. The effect Of CO2 pressure on the amorphous region of the poly(ethylene) was investigated by observing changes in the H-1 T-2 relaxation times of the polymer. These relaxation times decreased with increasing pressure, which was attributed to a decrease in mobility of the polymer chains as a result of compressive pressure.