bluuebunny/crossref_metadata_2025 huggingface dataset:
Variations in the requirement for v-SNAREs in GLUT4 trafficking in adipocytes
Authors: Zhao Ping , Yang Lu , Lopez Jamie A. , Fan Junmei , Burchfield James G. , Bai Li , Hong Wanjin , Xu Tao , James David E.
Published: September 2009

Vesicle transport in eukaryotic cells is regulated by SNARE proteins, which play an intimate role in regulating the specificity of vesicle fusion between discrete intracellular organelles. In the present study we investigated the function and plasticity of v-SNAREs in insulin-regulated GLUT4 trafficking in adipocytes. Using a combination of knockout mice, v-SNARE cleavage by clostridial toxins and total internal reflection fluorescence microscopy, we interrogated the function of VAMPs 2, 3 and 8 in this process. Our studies reveal that the simultaneous disruption of VAMPs 2, 3 and 8 completely inhibited insulin-stimulated GLUT4 insertion into the plasma membrane, due to a block in vesicle docking at the plasma membrane. These defects could be rescued by re-expression of VAMP2, VAMP3 or VAMP8 alone, but not VAMP7. These data indicate a plasticity in the requirement for v-SNAREs in GLUT4 trafficking to the plasma membrane and further define an important role for the v-SNARE proteins in pre-fusion docking of vesicles.
DUOX2-derived reactive oxygen species are effectors of NOD2-mediated antibacterial responses
Authors: Lipinski Simone , Till Andreas , Sina Christian , Arlt Alexander , Grasberger Helmut , Schreiber Stefan , Rosenstiel Philip
Published: September 2009

Generation of microbicidal reactive oxygen species (ROS) is a pivotal protective component of the innate immune system in many eukaryotes. NOD (nucleotide oligomerisation domain containing protein)-like receptors (NLRs) have been implicated as phylogenetically ancient sensors of intracellular pathogens or endogenous danger signals. NOD2 recognizes the bacterial cell wall component muramyldipeptide leading to NFκB and MAPK activation via induced proximity signalling through the serine-threonine kinase RIP2. In addition to the subsequent induction of cytokines and antimicrobial peptides, NOD2 has been shown also to exert a direct antibacterial effect. Using a fluorescence-based ROS detection assay we demonstrate controlled ROS generation as an integral component of NOD2-induced signalling in epithelial cells. We demonstrate that the NAD(P)H oxidase family member DUOX2 is involved in NOD2-dependent ROS production. Coimmunoprecipitation and fluorescence microscopy were used to show that DUOX2 interacts and colocalizes with NOD2 at the plasma membrane. Moreover, simultaneous overexpression of NOD2 and DUOX2 was found to result in cooperative protection against bacterial cytoinvasion using the Listeria monocytogenes infection model. RNAi-based studies revealed that DUOX2 is required for the direct bactericidal properties of NOD2. Our results demonstrate a new role of ROS as effector molecules of protective cellular signalling in response to a defined danger signal carried out by a mammalian intracellular NLR system.
Genomic, Tissue Expression, and Protein Characterization of pCLCA1, a Putative Modulator of Cystic Fibrosis in the Pig
Authors: Plog Stephanie , Mundhenk Lars , Klymiuk Nikolai , Gruber Achim D.
Published: September 2009

Recent studies have identified members of the CLCA (chloride channels, calcium-activated) gene family as potential modulators of the cystic fibrosis (CF) phenotype, but differences between the human and murine CLCA genes and proteins may limit the use of murine CF models. Recently established pig models of CF are expected to mimic the human disease more closely than the available mouse models do. Here, we characterized the porcine CLCA gene locus, analyzed the expression pattern and protein processing of pCLCA1, and compared it to its human ortholog, hCLCA1. The porcine CLCA gene family is located on chromosome 4q25, with a broad synteny with the human and murine clca gene loci, except for a pig-specific gene duplication of pCLCA4. Using pCLCA1-specific antibodies, the protein was immunohistochemically localized in mucin-producing cells, including goblet cells and mucinous glands in the respiratory and alimentary tracts. Similar to hCLCA1, biochemical characterization of pCLCA1 identified a secreted soluble protein that could serve as an extracellular signaling molecule or functional constituent of the protective mucous layers. The results suggest that pCLCA1 shares essential characteristics of hCLCA1, supporting the pig model as a promising tool for studying the modulating role of pCLCA1 in the complex pathology of CF.
Analysis of Cell Type-specific Expression of CK1ε in Various Tissues of Young Adult BALB/c Mice and in Mammary Tumors of SV40 T-Ag-transgenic Mice
Authors: Utz Anja C. , Hirner Heidrun , Blatz Annette , Hillenbrand Andreas , Schmidt Bernhard , Deppert Wolfgang , Henne-Bruns Doris , Fischer Dietmar , Thal Dietmar R. , Leithäuser Frank , Knippschild Uwe
Published: September 2009

Casein kinase 1 epsilon (CK1ε) is involved in various cellular processes, including cell growth, differentiation, and apoptosis, vesicle transport, and control of the circadian rhythm. Deregulation of CK1ε has been linked to neurodegenerative diseases and cancer. To better understand the cell type-specific functions of CK1ε, we determined its localization by immunhistochemistry in tissues of healthy, young adult BALB/c mice and in mammary tumors of SV40 T-antigen-transgenic mice. CK1ε expression was found to be highly regulated in normal tissues of endodermal, mesodermal, and ectodermal origin and in neoplastic tissue of mammary cancer. The data presented here give an overview of CK1ε reactivity in different organs under normal conditions and outline changes in its expression in mammary carcinomas. Our data suggest a cell/organ type-specific function of CK1ε and indicate that tumorigenic conversion of mammary glands in SV40 T-antigen-transgenic mice leads to downregulation of CK1ε. This manuscript contains online supplemental material at http://www.jhc.org . Please visit this article online to view these materials.
Physical Phenomena Concerning Corrosion Under Irradiation of Zr Alloys
Authors: Lemaignan C
Published: September 2009

The phenomena involved in the corrosion enhancement of Zr alloys under irradiation are analyzed. Among the basic mechanisms concerned, some are related to changes in microstructure of the alloy due to irradiation (precipitate evolution under irradiation and amorphous transformation), others to the transformation of the oxide layer (ZrO2) induced by neutron damage (irradiation-induced phase transformation of the zirconia). The effect of water chemistry and of the ionizing γ photons on the insulating zirconia will also be discussed.
Alternative Zr Alloys with Irradiation Resistant Precipitates for High Burnup BWR Application
Authors: Garzarolli F , Ruhmann H , Van Swam L
Published: September 2009

In the core of BWRs, the second-phase particles (SPP) of Zircaloy-2 and Zircaloy-4, the Zr(FeCr)2 and the Zr2(FeNi) phase, release Fe and dissolve. The degree of dissolution depends on initial size and fluence. These SPP, however, are important for the corrosion behavior of Zircaloy. Zircaloy shows an increase of corrosion at a certain burnup, depending on the initial SPP size and fast neutron fluence. Only Zr alloys with irradiation resistant SPP avoid this type of increased corrosion completely.

Two types of irradiation resistant materials were considered. One is a Zr-Sn-Fe alloy containing the Zr3Fe phase, which is irradiation resistant under BWR conditions. The other material is a Zr-Sn-Nb alloy containing the irradiation resistant β-Nb phase. In-BWR tests have shown that a Sn content of >0.8% is mandatory to minimize the nodular corrosion. Two prototypes of irradiation resistant alloys, Zr1.3Sn0.25-0.3 Fe and Zr1Sn2-3Nb, were irradiated in a BWR for 1372 days to a fast fluence of 9 x 1021n/cm2 (E > 1 MeV).

These irradiation tests showed that Zr1.3Sn0.25-0.3 Fe has a little lower resistance against nodular corrosion than optimized LTP (Low Temperature Process) Zircaloy-2/4 and revealed that Zr1Sn2-3Nb is superior to LTP Zircaloy-2/4 with respect to nodular and shadow corrosion resistance.

The BWR corrosion resistance of Zr1Sn2-3Nb depends on heat treatment. The lowest corrosion was observed with material fabricated completely in the α-range, but also material manufactured in the lower (α+β)-range exhibits low corrosion. Material fabricated in the upper (α+β)-range showed a somewhat higher corrosion, a corrosion behavior similar to LTP Zircaloy-2/4. As far as final annealing is concerned, a long time annealing at 540°C is superior to a standard recrystallization treatment (e.g., at 580°C), which still leads to a corrosion behavior that is better than stress relieved Zr1Sn2-3Nb.

Zr1Sn2-3Nb is resistant to shadow corrosion, when fabricated completely in the α-range. In other conditions, it shows a similar shadow corrosion behavior as Zircaloy-4.
The Influence of Material Variables on Corrosion and Deuterium Uptake of Zr-2.5Nb Alloy During Irradiation
Authors: McDougall GM , Urbanic VF
Published: September 2009

Current CANDU2 reactors use Zr-2.5Nb pressure tubes that are extruded at 1088 K, cold-drawn 27%, and autoclaved at 673 K for 24 h. This results in a metastable, two-phase microstructure consisting of elongated α-Zr grains surrounded by a network of β-Zr filaments. To develop a mathematical model of corrosion and deuterium ingress in pressure tubes, we have considered the impact of variables including: fast neutron flux, temperature, and the asfabricated microstructure and its evolution during irradiation.

Small specimens of Zr-2.5Nb are being exposed under CANDU water chemistry conditions in the Halden Boiling Water Reactor.3 The experiments involve fast neutron fluxes (E ≥ 1.05 MeV) of 0, 1.7, and 4.5 × 1017 n ∙ m-2 ∙ s-1, and temperatures of 523 and 598 K. Specimens have been prepared from pressure tube materials representative of all current CANDU reactors, materials subject to thermal decomposition of the β-Zr phase, and tubes extruded over a range of conditions.

Results from the first three years of the Halden test program are summarized. At both 523 and 598 K, tubes made of β-quenched material exhibit lower oxidation rates than those made from non-β-quenched materials. In short-term out-of-flux exposures at 523 K, three non-β quenched tubes appear to show linear oxidation kinetics. Similar behavior is not observed in tests conducted out-of-flux at 598 K, or in-flux at either temperature. At 598 K, β-quenched tubes exhibit significantly lower deuterium pickup rates than non-β-quenched tubes. When tested at 598 K, thermally aged specimens show declining oxidation and deuterium pickup rates with increasing β-Zr phase decomposition. At 523 K, the impact of thermal aging was less significant. Preliminary results from an “extrusion variable test” suggest that tubes fabricated according to the current CANDU specification show the best corrosion resistance.
Experimental Study and Preliminary Thermodynamic Calculations of the Pseudo-Ternary Zr-Nb-Fe-(O,Sn) System
Authors: Toffolon C , Brachet J-C , Servant C , Legras L , Charquet D , Barberis P , Mardon JP
Published: September 2009

Zirconium-niobium alloys, and especially the Framatome Zr-1%Nb-0 (M5™) alloy [1], are now considered to be the reference materials for application to the cladding tubes and structural components of PWR fuel assembly. Low contents of iron are present as impurity or intentionally introduced in such alloys, and, consequently, the precipitation of Zr-Nb-Fe intermetallic phases occur due to the very low solubility of iron in the α-Zr matrix (less than ∼100 ppm). Taking into account that these intermetallic precipitates may influence some of the alloy properties (corrosion resistance, irradiation growth …) and that the crystallographic structure, the chemical stoichiometry, and the temperature of precipitation/dissolution of these phases are not well established, it appeared necessary to get a better insight of the Zr-Nb-Fe-(O) phase diagram. For that reason, both thermodynamic calculations and associated experimental works were performed.

Different alloys with a niobium content ranging from 0.5 to 2 wt% and a Fe content from 0.03 to 0.75 wt% are considered. Two ternary intermetallic phases are present in these alloys: one has a hexagonal crystallographic structure (hc: a ∼ 0.54 nm, c ∼ 0.86 nm) and the other one has a face-centered cubic structure (fcc: a ∼ 1.21 nm). The chemical stoichiometry of both phases is determined by energy and wave dispersive spectrometries (EDS and WDS). The phase existence temperature range is determined by transmission electron microscopy (TEM) performed after heat treatments at different temperatures, by calorimetry, and by specific neutron diffraction experiments under heating/cooling. The results obtained using these experimental techniques show a good agreement. Moreover, the crystallographic space groups of the two intermetallic phases are determined using electron, X-ray, and neutron diffraction facilities in order to obtain a thermodynamic description of the Zr-Nb-Fe system. To assess the results obtained on dilute alloys (Zr > 97%), two Nb and Fe-enriched alloys were fabricated by CEZUS, with an intermetallic volume fraction higher than 80%.

Finally, a first thermodynamic calculation of the Zr-Nb-Fe(O) system is proposed, using all the experimental data obtained. Calculated and experimental data are then compared at different temperatures.
Predicting the In-Reactor Mechanical Behavior of Zr-2.5Nb Pressure Tubes from Postirradiation Microstructural Examination Data
Authors: Griffiths M , Davies PH , Davies WG , Sagat S
Published: September 2009

Postirradiation microstructure examinations of Zr-2.5Nb pressure tubes removed from service in CANDU™ reactors have shown clear trends in the dislocation structure and the state of the β-phase, as a function of operating temperature, neutron flux, and time. These microstructural parameters correlate well with changes in the mechanical properties. For example, the rapid increase in dislocation loop density in the early stages of irradiation corresponds with a rapid increase in tensile strength and DHC velocity, and a corresponding decrease in fracture toughness. There is also a strong negative correlation between the degree of β-phase decomposition and DHC velocity. In addition to the effects of microstructure evolution on the mechanical properties, changes in the a-type and c-component dislocation loop densities also affect irradiation deformation (creep and growth).

Statistical analyses of the irradiation microstructure data have been used to derive empirical relationships between dislocation densities and β-phase structure with temperature, flux, and time. The relationships thus derived are useful in predicting where the mechanical properties are most affected by the in-reactor operating conditions. The predictions are compared with mechanical test data for samples from various axial and circumferential locations of 42 pressure tubes removed from operating CANDU reactors. The results are discussed in terms of the mechanisms controlling tensile strength, fracture, delayed-hydride-cracking, and in-reactor deformation.
Characteristics of Hydride Precipitation and Reorientation in Spent-Fuel Cladding
Authors: Chung HM , Daum RS , Hiller JM , Billone MC
Published: September 2009

Transmission electron microscopy (TEM) was used to examine Zircaloy fuel ladding, either discharged from several PWRs and a BWR after irradiation to fluence levels of 3.3 to 8.6 × 1021 n cm-2 (E > 1 MeV) or hydrogen-charged and heat-treated under stress to produce radial hydrides; the goal was to determine the microstructural and crystallographic characteristics of hydride precipitation. Morphologies, distributions, and habit planes of various types of hydrides were determined by stereo-TEM. In addition to the normal macroscopic hydrides commonly observed by optical microscopy, small “microscopic” hydrides are present in spent-fuel cladding in number densities at least a few orders of magnitude greater than that of macroscopic hydrides. The microscopic hydrides, observed to be stable at least up to 333°C, precipitate in association with -type dislocations. While the habit plane of macroscopic tangential hydrides in the spent-fuel cladding is essentially the same as that of unirradiated unstressed Zircaloys, i.e., the {107}Zr plane, the habit plane of tangential hydrides that precipitate under high tangential stress is the {104}Zr plane. The habit plane of radial hydrides that precipitate under tangential stress is the {011} Zr pyramidal plane, a naturally preferred plane for a cladding that has 30° basal-pole texture. Effects of texture on the habit plane and the threshold stress for hydride reorientation are also discussed.
Impact of Irradiation Defects Annealing on Long-Term Thermal Creep of Irradiated ircaloy-4 Cladding Tube
Authors: Cappelaere C , Limon R , Gilbon D , Bredel T , Rabouille O , Bouffioux P , Mardon JP
Published: September 2009

Functions that can be allocated to cladding during interim storage depend on the evolution of cladding properties with time. The fuel rod cladding is strained by the end of-life internal fuel rod pressure (40–60 bars NTP) and the potential release of fission gases and helium during dry storage. Within the temperature range that is expected during dry interim storage, long-term creep under over-pressure of the cladding might probably be a relevant strain mechanism, which could lead to breaching.

Creep experiments were carried out on 4 cycles irradiated Cold Worked Stress Relieved (CWSR) Zircaloy-4 cladding under internal pressure within the temperature range of 470–520°C for up to 10 days, in order to estimate the eventual effect of a transient period at higher temperature on creep behavior during storage. Therefore, some of the tests consist of two periods: the first period at high temperature (470°C), followed by a second period at a lower temperature (320–400°C). A metallurgical characterization (TEM, optical microscopy) was carried out after the tests.

A significant impact of the stress level is observed at the temperature of 470°C on creep strain. Tertiary creep is reached after a few days for 100 or 120 MPa. The effect of a first period at 470°C on the next creep behavior at 400°C for 150 MPa is confirmed. The probable induced annealing of irradiation defects contributes to increase the secondary creep rate at 400°C. Moreover, the creep kinetics of the tests conducted to rupture show in all the cases a ductile rupture with ballooning instability, which might be partially the result of an annealing of irradiation defects.

The microscopic characterization confirms the hypothesis of a partial annealing of the irradiation defects after a period of 10 days at 470°C, which leads to a microstructure intermediate between irradiated and as-received CWSR condition, while a temperature of 520°C leads to a microstructure that looks like recrystallized Zircaloy-4 condition.

After the creep test, hydrides morphology, distribution, and orientation appear rather different from usual post-irradiation hydrides characteristics. The hydrides are distributed uniformly throughout the thickness of the tube. A cooling under mechanical loading influences the hydrides precipitation, particularly by leading to a radial “reorientation.” A stress level of 80 MPa during cooling is sufficient to lead to radial hydrides formation as hydrogen precipites in the cladding.
Influence of Zirconium Alloy Chemical Composition on Microstructure Formation and Irradiation Induced Growth
Authors: Shishov VN , Peregud MM , Nikulina AV , Shebaldov PV , Tselischev AV , Novoselov AE , Kobylyansky GP , Ostrovsky ZE , Shamardin VK
Published: September 2009

The studies of the dislocation structure, phase, and microchemical compositions of alloy Zr-1Nb-1.2Sn-0.35Fe (E635) and its modifications containing Fe from 0.15 to 0.65% were carried out before and after research reactor irradiation at ∼350°C to maximal fluence of ∼1027 m-2 (E > 0.1 MeV) and at ∼60°C. The size and concentration of the -type loops depend on the alloy composition and fluence and saturate even at low doses (<1 dpa). The evolution of the -component dislocation structure in recrystallized alloys of E365 type is determined by the chemical and phase compositions of alloys specifically, by the Fe/Nb ratio and the threshold dose, and is consistent with the irradiation growth strain acceleration. In E635 alloy containing 0.15%Fe the accelerated growth is observed after the dose of 15 dpa and is attended with the evolution of the  dislocation structure which is similar to Zr-1Nb (E110) alloy behavior. The irradiation induced growth of E635 type alloy containing 0.65% Fe is similar to that of E635 having the normal composition; no  dislocations are observed up to the dose of 20 dpa. E635 alloy contains precipitates Zr(Nb1-xFex)2 (HCP) as the basic excess phase and individual (Zr,Nb)2Fe (FCC) precipitates; in 0.15%Fe alloy aside from Zr(Nb,Fe)2 also β-Nb (BCC) particles precipitate, while 0.65%Fe alloy contains Zr(Nb,Fe)2 and (Zr,Nb)2Fe particles. Irradiation at 330 –350 °C does not effect an amorphization of β-Nb or Zr(Nb,Fe)2 precipitates; however, at higher fluences the β-Nb phase becomes depleted in Nb and Zr(Nb,Fe)2 in Fe. Irradiation at 60°C leads to the amorphization of Zr(Nb,Fe)2 in E635. The analysis revealed that the key factors promoting a delay in the accelerated irradiation growth in Zr-Nb-Fe-Sn alloys are the composition of (Nb,Fe,Sn) solid solution and the Fe/Nb ratio in alloys.
Radioactivity Inspections Applied to the Steelmaking Industry
Authors: Buoro Stelvio , Giurgevich Marco
Published: September 2009

The recycling of exhausted or end-of-life materials in industry is pursued worldwide to save natural resources and reduce pollution. The utilization of scrap as raw material in the steelmaking industry is a well-assessed technology. Nevertheless, recycled materials must be “free” from dangerous elements or compounds and particularly from hazardous levels of radioactivity. Typical problems to be faced in the electrical steelmaking industry relevant to radioactivity levels and measurements techniques are discussed in this paper.
Performance Evaluation of “Duplex Hardened” Bearings for Advanced Turbine Engine Applications
Authors: Streit Edgar , Brock Joe , Poulin Patrick
Published: September 2009

Reliability is one of the most important competitive factors in aeroengines. Engine manufacturers have to provide guarantees for maintenance cost and dispatch reliability. Failures of mainshaft and gearbox bearings can represent a major debit to overall engine reliability. Duplex hardening (conventional hardening followed by special nitriding) has the potential to provide the bearing performance improvements necessary to yield increased engine reliability and reduced cost of ownership. The bearing rig tests performed demonstrate superior performance of duplex hardened M50 and M50NiL bearings over conventional M50 and MSONiL bearings under various operating conditions. Rig tests evaluating a wide range of operating conditions, such as high load, low or boundary lubrication, heavily contaminated lubrication, and oil off were performed. Additional tests were completed to evaluate the spall propagation behavior of duplex hardened bearings in comparison to conventional steel bearings. The results showed that the main benefits of using duplex hardened bearings arise in low or boundary lubrication conditions and contaminated lubrication conditions. The spall propagation tests showed that spall propagation rates are slower for duplex hardened M50 and M50NiL bearing components, hence allowing more time until catastrophic bearing failure in an aeroengine and other applications.
Phase Equilibria and Thermodynamic Properties of Lime-Iron Oxide Melts Containing up to 30 Percent SiO2: 1450 and 1550 C Sections
Authors: Timucin M. , Morris A. E.
Published: September 2009

This paper is a brief presentation of research work on the effect of lime on the thermodynamic properties of synthetic basic oxygen steelmaking slags saturated with lime. It provides a basis for understanding the fluxing behavior of lime and other constituents in such slags. Solid solutions of ferrous iron in lime also have been investigated, particularly with respect to an improvement in the resistance of lime to hydration.
Load-deflection Field Test of 27-inch (675-mm) PVC (Polyvinyl Chloride) Pipe
Authors: Howard Amster K.
Published: September 2009

The Bureau of Reclamation constructed a special test section of 27-inch (675-mm) diameter PVC (polyvinyl chloride) pipe in November 1987 near Elba, Nebraska. Measurements were made of pipe deflections, pipe invert elevations, soil properties, and in-place unit weights. Pipe deflections will be continually monitored for several years. This paper describes the installation and pipe deflection measurements through the 2-year reading.
Influence of Water Composition on Corrosion in High-Temperature, High-Purity Water
Authors: Wroughton Donald M. , Seamon James M. , Brown Paul E.
Published: September 2009

Corrosion tests have indicated that, except for pH, water composition within the range of variables studied has a minor influence on corrosion rates of carbon steel under conditions which may exist in the primary coolant of water-cooled and moderated reactors. Water conditions, however, cannot be considered unimportant, because (a) the range of variables studied has been limited by considerations of induced radioactivity and radiation stability of possible corrosion inhibitors, (b) special considerations associated with the primary coolant technology of reactor systems make water conditions important, and (c) the influence of water condition on the characteristics of the corrosion products formed may be of considerable concern.

Some inhibitors were effective in reducing corrosion rates in autoclave tests but unsuitable for reactor operation. The possibility is discussed of using inhibitors during precritical operation of a new system to minimize the high corrosion rates normally experienced with new surfaces.

The relationship existing between water condition and corrosion product behavior in the primary system of a water-cooled reactor is noted. Possible undesirable results of the adverse behavior of system corrosion products are: (1) fouling of the reactor core or other heat transfer surfaces by deposition, (2) fouling or wear of valves or mechanisms which operate in the primary system water, and (3) rapid pressure drop build-up on some types of filters used to remove the corrosion products.

Current water technology studies have as their objective the operation of the primary systems of water-cooled and moderated reactors with the minimum control of water composition compatible with trouble-free operation. The establishment of minimum water-quality control requires knowledge concerning variations in water composition that may occur in reactor operation and how these variations affect plant integrity.
Field Tests for Determining Permeability of Soil Strata
Authors: Golder H. Q. , Gass A. A.
Published: September 2009

The subject of permeability of soil strata is approached from the civil engineering point of view, which is fundamentally different from the, perhaps more usual, hydrological approach. The soils dealt with are silts, sands, and gravels, but not clays. A knowledge of the coefficient of permeability is needed in the design of dams on permeable foundations and for construction purposes when an area has to be de-watered inside cofferdams or in an excavation, and in many grouting problems. Methods of measuring permeability in the field—borehole tests, pressure dissipation tests, grain size tests, seasonal variation in groundwater levels and pumping tests—are discussed. The methods are compared by reference to work done on actual sites, in particular on a site which involved the design and construction problems for a dam on a pervious foundation. It was found that the coefficients of permeability estimated by the various techniques were in reasonable agreement.
Introduction
Authors: Hamilton C. E.
Published: September 2009

This manual is intended as brief reference source of information on water. It will not replace an adequate library on the subject, but it does provide basic information for routine use and cites references to the technical literature, thus serving as a point of departure for more specific and detailed studies. For executives and administrators, it offers information on the influence of water on industries in which it is used as a raw material or in conjunction with manufacturing operations. The influence of water on various industries ranges from that in the paper industry, where large volumes of water of good quality are used, to industries where only incidental quantities and qualities of water are needed. The manual should serve as a guide to the nature of water planning required at the executive and investment levels of management. At no level, however, can the quantity and quality of available water be disregarded as it relates to the requirements of each process or manufacturing operation for today and for the foreseeable future. Operations personnel will find the manual to be a guide to the significance of the treatment being applied. Combined with the general discussion of the problems arising from water use are the specific details of control procedures and instructions for such critical operations as sampling water under the various conditions and in the several forms in which it is used. The manual may be useful as a text for plant operator training and for the indoctrination of technologists from other fields. Chemists and other technologists who have special knowledge of water can use the manual as a reference for specific information not published elsewhere.
Reactive Astrocytes Form Scar-Like Perivascular Barriers to Leukocytes during Adaptive Immune Inflammation of the CNS
Authors: Voskuhl Rhonda R. , Peterson R. Scott , Song Bingbing , Ao Yan , Morales Laurie Beth J. , Tiwari-Woodruff Seema , Sofroniew Michael V.
Published: September 2009

Factors that regulate leukocyte entry and spread through CNS parenchyma during different types of CNS insults are incompletely understood. Reactive astrocytes have been implicated in restricting the spread of leukocytes from damaged into healthy parenchyma during the acute and local innate inflammatory events that follow CNS trauma, but the roles of reactive astrocytes during the chronic and widespread CNS inflammation associated with adaptive or acquired immune responses are uncertain. Here, we investigated the effects of transgenically targeted ablation of proliferating, scar-forming reactive astrocytes on the acquired immune inflammation associated with experimental autoimmune encephalitis (EAE). In wild-type mice with EAE, we found that reactive astrocytes densely surrounded perivascular clusters of leukocytes in a manner reminiscent of astrocyte scar formation after CNS trauma. Transgenically targeted ablation of proliferating astrocytes disrupted formation of these perivascular scars and was associated with a pronounced and significant increase in leukocyte entry into CNS parenchyma, including immunohistochemically identified macrophages, T lymphocytes and neutrophils. This exacerbated inflammation was associated with a substantially more severe and rapidly fulminant clinical course. These findings provide experimental evidence that reactive astrocytes form scar-like perivascular barriers that restrict the influx of leukocytes into CNS parenchyma and protect CNS function during peripherally initiated, acquired immune inflammatory responses in the CNS. The findings suggest that loss or disruption of astrocyte functions may underlie or exacerbate the inflammation and pathologies associated with autoimmune diseases of the CNS, including multiple sclerosis.
Activity of Hb9 Interneurons during Fictive Locomotion in Mouse Spinal Cord
Authors: Kwan Alex C. , Dietz Shelby B. , Webb Watt W. , Harris-Warrick Ronald M.
Published: September 2009

Hb9 interneurons (Hb9 INs) are putative components of the mouse spinal locomotor central pattern generator (CPG) and candidates for the rhythm-generating kernel. Studies in slices and hemisected spinal cords showed that Hb9 INs display TTX-resistant membrane potential oscillations, suggesting a role in rhythm generation. To further investigate the roles of Hb9 INs in the locomotor CPG, we used two-photon calcium imaging in thein vitroisolated whole neonatal mouse spinal cord preparation to record the activity of Hb9 INs, which were subsequently stained for unambiguous genetic identification. We elicited fictive locomotion by transmitter application or by electrically stimulating the caudal tip of the spinal cord. Although most Hb9 INs were rhythmically active during fictive locomotion, their activity was sparse and they failed to fire with each cycle of the episode. If Hb9 INs are the principal pacemakers of the CPG in the hemisegment in which they are located, they should direct the firing of motor neurons, with their activity preceding that of their ipsilateral segmental ventral roots. Instead, during each locomotor cycle, onset of Hb9 IN activity lagged behind the onset of the ipsilateral ventral root burst by a mean phase of 0.21 during electrical stimulation and 0.28 during transmitter application. Whole-cell recordings in intact and hemisected spinal cords confirmed the imaging results. Our data suggest that Hb9 INs participate in fictive locomotion, but the delayed onset of activity relative to ipsilateral motoneurons suggests that Hb9 INs are unlikely to be the sole intrasegmental rhythm-generating kernel of the CPG.
Antidepressant Actions of Histone Deacetylase Inhibitors
Authors: Covington Herbert E. , Maze Ian , LaPlant Quincey C. , Vialou Vincent F. , Ohnishi Yoshinori N. , Berton Olivier , Fass Dan M. , Renthal William , Rush Augustus J. , Wu Emma Y. , Ghose Subroto , Krishnan Vaishnav , Russo Scott J. , Tamminga Carol , Haggarty Stephen J. , Nestler Eric J.
Published: September 2009

Persistent symptoms of depression suggest the involvement of stable molecular adaptations in brain, which may be reflected at the level of chromatin remodeling. We find that chronic social defeat stress in mice causes a transient decrease, followed by a persistent increase, in levels of acetylated histone H3 in the nucleus accumbens, an important limbic brain region. This persistent increase in H3 acetylation is associated with decreased levels of histone deacetylase 2 (HDAC2) in the nucleus accumbens. Similar effects were observed in the nucleus accumbens of depressed humans studied postmortem. These changes in H3 acetylation and HDAC2 expression mediate long-lasting positive neuronal adaptations, since infusion of HDAC inhibitors into the nucleus accumbens, which increases histone acetylation, exerts robust antidepressant-like effects in the social defeat paradigm and other behavioral assays. HDAC inhibitor [N-(2-aminophenyl)-4-[N-(pyridine-3-ylmethoxy-carbonyl)aminomethyl]benzamide (MS-275)] infusion also reverses the effects of chronic defeat stress on global patterns of gene expression in the nucleus accumbens, as determined by microarray analysis, with striking similarities to the effects of the standard antidepressant fluoxetine. Stress-regulated genes whose expression is normalized selectively by MS-275 may provide promising targets for the future development of novel antidepressant treatments. Together, these findings provide new insight into the underlying molecular mechanisms of depression and antidepressant action, and support the antidepressant potential of HDAC inhibitors and perhaps other agents that act at the level of chromatin structure.
Spatial Spread of the Local Field Potential and its Laminar Variation in Visual Cortex
Authors: Xing Dajun , Yeh Chun-I , Shapley Robert M.
Published: September 2009

We developed a new method to estimate the spatial extent of summation, the cortical spread, of the local field potential (LFP) throughout all layers of macaque primary visual cortex V1 by taking advantage of the V1 retinotopic map. We mapped multi-unit activity and LFP visual responses with sparse-noise at several cortical sites simultaneously. The cortical magnification factor near the recording sites was precisely estimated by track reconstruction. The new method combined experimental measurements together with a model of signal summation to obtain the cortical spread of the LFP. This new method could be extended to cortical areas that have topographic maps such as S1 or A1, and to cortical areas without functional columnar maps, such as rodent visual cortex. In macaque V1, the LFP was the sum of signals from a very local region, the radius of which was on average 250 μm. The LFP's cortical spread varied across cortical layers, reaching a minimum value of 120 μm in layer 4B. An important functional consequence of the small cortical spread of the LFP is that the visual field maps of LFP and MUA recorded at a single electrode site were very similar. The similar spatial scale of the visual responses, the restricted cortical spread, and their laminar variation led to new insights about the sources and possible applications of the LFP.
Striatal Expression of a Calmodulin Fragment Improved Motor Function, Weight Loss, and Neuropathology in the R6/2 Mouse Model of Huntington's Disease
Authors: Dai Ying , Dudek Nichole L. , Li Qian , Fowler Stephen C. , Muma Nancy A.
Published: September 2009

Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder, caused by a polyglutamine expansion in the huntingtin protein (htt). Increasing evidence suggests that transglutaminase (TGase) plays a critical role in the pathophysiology of HD possibly by stabilizing monomeric, polymeric and aggregated htt. We previously reported that in HEK293 and SH-SY5Y cells expression of a calmodulin (CaM)-fragment, consisting of amino acids 76-121 of CaM, decreased binding of CaM to mutant htt, TGase-modified htt and cytotoxicity associated with mutant htt and normalized intracellular calcium release. In this study, an adeno-associated virus (AAV) that expresses the CaM-fragment was injected into the striatum of HD transgenic R6/2 mice. The CaM-fragment significantly reduced body weight loss and improved motor function as indicated by improved rotarod performance, longer stride length, lower stride frequency, fewer low mobility bouts and longer travel distance than HD controls. A small but insignificant increase in survival was observed in R6/2 mice with CaM-fragment expression. Immunoprecipitation studies show that expression of the CaM-fragment reduced TGase-modified htt in the striatum of R6/2 mice. The percentage of htt-positive nuclei and the size of intranuclear htt aggregates were reduced by the CaM-fragment without striatal volume changes. The effects of CaM-fragment appear to be selective, as activity of another CaM-dependent enzyme, CaM-dependent kinase II, was not altered. Moreover, inhibition of TGase-modified htt was substrate-specific since overall TGase activity in the striatum was not altered by treatment with the CaM-fragment. Together, these results suggest that disrupting CaM–htt interaction may provide a new therapeutic strategy for HD.
PP2A and GSK-3β Act Antagonistically to Regulate Active Zone Development
Authors: Viquez Natasha M. , Füger Petra , Valakh Vera , Daniels Richard W. , Rasse Tobias M. , DiAntonio Aaron
Published: September 2009

The synapse is composed of an active zone apposed to a postsynaptic cluster of neurotransmitter receptors. EachDrosophilaneuromuscular junction comprises hundreds of such individual release sites apposed to clusters of glutamate receptors. Here, we show that protein phosphatase 2A (PP2A) is required for the development of structurally normal active zones opposite glutamate receptors. When PP2A is inhibited presynaptically, many glutamate receptor clusters are unapposed to Bruchpilot (Brp), an active zone protein required for normal transmitter release. These unapposed receptors are not due to presynaptic retraction of synaptic boutons, since other presynaptic components are still apposed to the entire postsynaptic specialization. Instead, these data suggest that Brp localization is regulated at the level of individual release sites. Live imaging of glutamate receptors demonstrates that this disruption to active zone development is accompanied by abnormal postsynaptic development, with decreased formation of glutamate receptor clusters. Remarkably, inhibition of the serine-threonine kinase GSK-3β completely suppresses the active zone defect, as well as other synaptic morphology phenotypes associated with inhibition of PP2A. These data suggest that PP2A and GSK-3β function antagonistically to control active zone development, providing a potential mechanism for regulating synaptic efficacy at a single release site.
Therapeutic analysis in Chinese patients with thyrotoxic periodic paralysis over 6 years
Authors: Shiang Jeng-Chuan , Cheng Chih-Jen , Tsai Ming-Kai , Hung Yi-Jen , Hsu Yu-Juei , Yang Sung-Sen , Chu Shi-Jye , Lin Shih-Hua
Published: September 2009

Objective

To characterize the course of therapy in a large cohort of Chinese patients with thyrotoxic periodic paralysis (TPP), a reversible electrolyte emergency fraught with therapeutic challenges.

Design and methods

In this prospective interventional study, 78 patients with TPP (75 males and three females with an age range of 16–48 years) were consecutively enrolled over a 6-year period. Intravenous KCl at a rate of 10 mmol/h was administered until muscle strength recovered. Serum potassium (K+) and phosphorus concentrations were measured hourly during the paralytic attack and for 6 h after recovery.

Results

The serum potassium (K+) on attack was 2.1±0.2 mmol/l. The dose of KCl administered to restore muscle strength was 63±32 mmol, and peak serum K+ concentration after recovery was 5.3±0.5 mmol/l. A paradoxical fall in serum K+ concentration >0.1 mmol/l difference between presentation and treatment nadir was observed in approximately one-fourth of TPP patients (n=20). These patients had significantly higher serum-free thyroxine concentration, systolic blood pressure, and heart rate on presentation, as well as serum phosphate concentration on recovery. They not only needed much more KCl supplementation (104±34 vs 48±19 mmol, P<0.001), but also had significantly more severe rebound hyperkalemia (5.8±0.5 vs 5.1±0.4 mmol/l, P<0.001) on recovery than those who did not have paradoxical hypokalemia. There was a positive correlation between the dose of KCl administered and the difference between peak and nadir serum K+ (Δ K+) (r=0.68, P<0.001).

Conclusions

TPP patients who do not develop paradoxical hypokalemia need a smaller KCl dose to achieve recovery, whereas those who develop paradoxical hypokalemia have more severe hyperthyroidism and hyperadrenergic activity and may require blockage of intracellular K+ shift to prevent rebound hyperkalemia.
Is the metalloendopeptidase EC 3.4.24.15 (EP24.15), the enzyme that cleaves luteinizing hormone-releasing hormone (LHRH), an activating enzyme?
Authors: Cleverly Kirsty , Wu T John
Published: September 2009

LHRH (GNRH) was first isolated in the mammalian hypothalamus and shown to be the primary regulator of the reproductive neuroendocrine axis comprising of the hypothalamus, pituitary and gonads. LHRH acts centrally through its initiation of pituitary gonadotrophin release. Since its discovery, this form of LHRH (LHRH-I) has been shown to be one of over 20 structural variants with a variety of roles in both the brain and peripheral tissues. LHRH-I is processed by a zinc metalloendopeptidase EC 3.4.24.15 (EP24.15) that cleaves the hormone at the fifth and sixth bond of the decapeptide (Tyr5-Gly6) to form LHRH-(1–5). We have previously reported that the auto-regulation of LHRH-I (GNRH1) gene expression and secretion can also be mediated by itself and its processed peptide, LHRH-(1–5), centrally and in peripheral tissues. In this review, we present the evidence that EP24.15 is the main enzyme of LHRH metabolism. Following this, we look at the metabolism of other neuropeptides where an active peptide fragments is formed during degradation and use this as a platform to postulate that EP24.15 may also produce an active peptide fragment in the process of breaking down LHRH. We close this review by the role EP24.15 may have in regulation of the complex LHRH system.
From Nominal to Substantive Democracy: The Role and Design of Election Management Bodies
Authors: Trebilcock Michael , Chitalkar Poorvi
Published: September 2009

The last quarter of the century has seen a wave of new democracies. However in many democracies, the electoral process is fraudulent and powerful incumbents manipulate elections. This calls for a distinction to be drawn between nominal and substantive democracies and this paper focuses on such nominal democracies, where elections are often a façade and democracy is rendered meaningless. Instances of fraudulent elections are rampant in the recent history of many developing countries, creating a need to reform electoral processes. Numerous factors must co-exist for the existence of free and fair elections but this paper focuses on independent and impartial institutions of election administration. An effective election management body (EMB) must be independent of the executive, operate without partiality to any political group, have a broad mandate and enjoy financial autonomy. Against this backdrop, this paper surveys the electoral experiences across five regions - Asia, Latin America, Africa, Central and Eastern Europe and the Middle-East. Successful electoral experiences are found to be associated with independent and impartial EMB's that are vested with broad mandates. Such EMB's have succeeded not only in conducting free and fair elections but also enhancing respect for the electoral process. On the other hand, failures of free and fair elections can be traced back to poorly functioning EMB's that fall short of normative benchmarks. This paper proposes reforms to EMB's as a step towards establishing credible and legitimate electoral processes.
Methanol Electro-Oxidation on Pt-Ru Alloy Nanoparticles Supported on Carbon Nanotubes
Authors: Li Liang , Xing Yangchuan
Published: September 2009

Carbon nanotubes (CNTs) have been investigated in recent years as a catalyst support for proton exchange membrane fuel cells. Improved catalyst activities were observed and attributed to metal-support interactions. We report a study on the kinetics of methanol electro-oxidation on CNT supported Pt-Ru alloy nanoparticles. Alloy catalysts with different compositions, Pt53Ru47/CNT, Pt69Ru31/CNT and Pt77Ru23/CNT, were prepared and investigated in detail. Experiments were conducted at various temperatures, electrode potentials, and methanol concentrations. It was found that the reaction order of methanol electro-oxidation on the PtRu/CNT catalysts was consistent with what has been reported for PtRu alloys with a value of 0.5 in methanol concentrations. However, the electro-oxidation reaction on the PtRu/CNT catalysts displayed much lower activation energies than that on the Pt-Ru alloy catalysts unsupported or supported on carbon black (PtRu/CB). This study provides an overall kinetic evaluation of the PtRu/CNT catalysts and further demonstrates the beneficial role of CNTs.