bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of Creep Relaxation on the Delayed Hydride Cracking Behavior of Irradiated Zirconium 2.5%Wt Niobium Pressure Tube Material
Authors: Chaput Heather , Leitch Brian W. , Metzger Don R.
Published: July 2008

Surface scratches and flaws encountered in CANDU nuclear pressure tubes must be evaluated to ensure that a cracking mechanism, called delayed hydride cracking (DHC), is not initiated. The stress concentration due to a flaw can cause diffusion of hydrogen and precipitation of zirconium hydride at the flaw tip. The presence of a hydride results in reduced fracture resistance in a local region where high stress prevails. In many cases, flaws exist for an extended period of time before the hydrogen content in the base material is sufficient to form a hydride. In this situation high stress creep can significantly relax the local stress at the flaw tip. The assessment of flaws on the basis of local stress distribution not considering creep is expected to be overly conservative, and may result in unnecessary remedial action in reactor operation and maintenance procedures. An experimental program has been developed to isolate and quantify the effect of creep on DHC in irradiated Zr-2.5%Nb pressure tube material. As part of this program, the thermal and load histories relevant to reactor operating conditions have been considered, and initial experimental results indicate that the action of creep increases the threshold load for crack initiation. Finite element analysis of creep relaxation around a hydride also supports the experimental results, and a fracture initiation model is applied to the experimental conditions in order to establish an analytical trend for the effect of creep. The quantitative effect predicted by the model is in reasonable agreement with the experimental results, and an improved, less conservative assessment procedure that accounts for creep is deemed to be practical.
NDE Assessment of PWSCC in Control Rod Drive Mechanism Housings
Authors: Doctor Steven R. , Cumblidge Stephen E. , Schuster George J. , Harris Robert V. , Crawford Susan L.
Published: July 2008

Studies being conducted at the Pacific Northwest National Laboratory (PNNL) in Richland, Washington are focused on assessing the effectiveness of nondestructive examination (NDE) techniques for inspecting control rod drive mechanism (CRDM) nozzles and J-groove weldments. The primary objective of this work is to provide information to the United States Nuclear Regulatory Commission (US NRC) on the effectiveness of NDE methods as related to the in-service inspection of CRDM nozzles and J-groove weldments, and to enhance the knowledge base of primary water stress corrosion cracking (PWSCC) through destructive characterization of the CRDM assemblies. In describing two CRDM assemblies removed from service, decontaminated, and then used in a series of NDE measurements, this paper will address the following questions: 1) What did each technique detect?, 2) What did each technique miss?, and 3) How accurately did each technique characterize the detected flaws? Two CRDM assemblies including the CRDM nozzle, the J-groove weld, buttering, and a portion of the ferritic head material were selected for this study. One contained suspected PWSCC, based on in-service inspection data and through-wall leakage; the other contained evidence suggesting through-wall leakage, but this was unconfirmed. The two CRDMs used in this study were cut from a pressure vessel head that has since been replaced. The selected NDE measurements follow standard industry techniques for conducting in-service inspections of CRDM nozzles and the crown of the J-groove welds and buttering. In addition, laboratory based NDE methods were employed to conduct inspections of the CRDM assemblies, with particular emphasis on inspecting the J-groove weld and buttering. This paper will also describe the NDE methods used and discuss the NDE results. Future work will involve using the results from these NDE studies to guide the development of a destructive characterization plan to reveal the crack morphology and a comparison of the degradation found by the destructive evaluation with the recorded NDE responses.
Simulation of Acoustical Response Using Rayleigh Method
Authors: Alia Ahlem , Souli Mhamed
Published: July 2008

The Boundary Element Method is one of the most used techniques for the simulation of acoustic problems especially for external ones. However, it leads to large computational time because of the complex character of the resulting linear system and the calculation of its different terms by surface integration. In this paper, the Rayleigh method is used to calculate the acoustical pressure at any point in the space. This method is very fast since it does not need to construct and to solve a linear system.
Experimental Investigation for a Suitable Supercritical Reaction Container
Authors: Maehara Hironori , Itoh Shigeru , Hemuki Yosuke
Published: July 2008

Supercritical fluid is the fluid in the state where the limit (critical point) of temperature pressure that a liquid and gas coexist was exceeded. This is a fluid to which it has a big kinetic energy similar to the gas molecule, and the high molecular density that equals a liquid has it. In fact, supercritical fluid has dissolution power like a liquid, and has diffusivity like a gas. Therefore, supercritical fluid has a possibility of becoming the ideal solvent. The experiment purpose is a resolution of the organism by the supercritical reaction. We designed the supercritical reaction container with which both of the fluid, water and carbon dioxide, can correspond. Supercritical demanded the severe resisting pressure, heatproof, and resistance to corrosion with the container. A supercritical temperature of water is 374.1°C, and supercritical pressure is 22.06 MPa. IT was designed in consideration of the safety rate to resist the temperature of 500°C and the pressure of 50MPa. We designed the container of the batch type with comparatively easy structure, and made of the stainless steel and the amount of the contents is 375ml. Next, the condition of the heating furnace is described. Power consumption is 1500W, and the maximum temperature is 600°C. Supercritical state is controlled at the temperature. Heating it raises the pressure in the container and it reaches a supercritical temperature and supercritical pressure. Finally in the experiment, it was confirmed to endure even 25MPa.
Basic Study on Pressure Vessel for Food Processing by Shock Loading
Authors: Oda Asuka , Watanabe Toshiaki , Itoh Shigeru
Published: July 2008

Underwater shockwave is easily generated by means of explosion of explosive and by means of high voltage electric discharges in water. It has characteristics of high pressure, very short duration of action, and permeation [1]. Therefore, underwater shockwave can destroy only materials inside without destroying their outside. We tried using application of underwater shockwave to some foods as food processing device. At this experiment, foods were applied underwater shockwave by using detonating fuse and electric detonator in water tank. Foods sample was apples, Japanese radishes, and burdocks. In the result, foods were made soft. From result of apples, we easily got juice by squeezing by woman’s power without grating up apples. And there was difference of content of polyphenols in juice between application underwater shockwave to apples and non-application. Extraction of Japanese radish was improved. From these experimental results, we suggest necessity spec of shockwave processing vessel for food processing.
Application of a Dynamic Stress Theory to Pipe Leaks
Authors: Leishear Robert A.
Published: July 2008

Leaks in system piping used to transfer radioactive waste were attributed to water hammer. Ball valves leaked on several occasions and the cause of failure was not obvious. Facility records were used to determine the facility status at the time the leaks occurred. For one particular leak, valve manipulations controlling flow were shown to be coincident to the time of leak. The fluid transient pressures were calculated, and once the maximum pressures were established, the stresses on the equipment could be discerned. Water hammer was concluded to be the failure mechanism. To eliminate this failure mechanism, procedural and equipment modifications were made and further leaks have been eliminated.
Sloshing in a Cylindrical Liquid Storage Tank With a Floating Roof Under Seismic Excitation
Authors: Matsui Tetsuya
Published: July 2008

An analytical solution is presented to predict the sloshing response of a cylindrical liquid storage tank with a floating roof under seismic excitation. The contained liquid is assumed to be inviscid, incompressible and irrotational, while the floating roof is idealized as an isotropic elastic plate with uniform stiffness and mass. The dynamic interaction between the floating roof and the liquid is taken into account exactly within the framework of linear potential theory. By expanding the response of the floating roof into free vibration modes in air and employing the Fourier-Bessel expansion method in cylindrical coordinates, the solution is obtained in an explicit form which is useful for parametric understanding of the sloshing behavior and preliminary study in the early design stage. Numerical results are also provided to investigate the effect of the stiffness and mass of the floating roof on the sloshing response.
An Evaluation of Fuel Rod Fretting Wear in Spacer Grid With Conformal Shape
Authors: Jang Young Ki , Park Nam Kyu , Kim Jae Ik , Kim Kyu Tae , Lee Chong Chul , Cho Kyu Zong
Published: July 2008

Turbulent flow-induced vibration in nuclear fuel may cause fretting wear of fuel rod at grid support locations. An advanced nuclear fuel for Korean PWR standard nuclear power plants (KSNPs), has been developed to get higher performance comparing to the current fuel considering the safety and economy. One of the significant features of the advanced fuel is the conformal shape in mid grid springs and dimples, which are developed to diminish the fretting wear failure. Long-term hydraulic tests have been performed to evaluate the fretting wear of the fuel rod with the conformal springs and dimples. Wear volume is a measure to predict the fretting wear performance. The shapes of a lot of scars are non-uniform such as wedge shapes, and axially non-symmetric shapes, etc., depending on the contact angle between fuel rod and springs/dimples. In addition, conformal springs and dimples make wear scars wide and thin comparing to conventional ones with convex shape. It is found that wear volumes of these kinds of non-uniform wear scars are over-predicted when the traditionally used wear depth-dependent volume calculation method is employed. In order to predict wear volume more accurately, therefore, the measuring system with high accuracy has been used and verified by the known wear volumes of standard specimens. The wear volumes of the various wear scars have been generated by the measuring system and used for predicting the fretting wear-induced failure time. Based on new evaluation method, it is considered that the fretting wear-induced fuel failure duration with this conformal grid has increased up to 8 times compared to the traditionally used wear depth-dependent volume calculation method.
Thermal Fatigue Appears to be More Damaging Than Uniaxial Isothermal Fatigue: A Complete Analysis of the Results Obtained on the CEA Thermal Fatigue Device Splash
Authors: Fissolo Antoine , Amiable Se´bastien , Vincent Ludovic , Chapuliot Ste´phane , Constantinescu Andrei , Stelmaszyk Jean Marc
Published: July 2008

Thermal fatigue sometimes occurs in different types of nuclear reactor components. To estimate the crack initiation damage, uniaxial fatigue curves are often used. They were deduced from strain control tests using normalised cylindrical specimens. However, for in-service components, thermal loadings induce biaxial mechanical loadings. In that frame, the questioning of an eventual influence of the triaxiality factor on fatigue damage can be asked. To investigate differences between uniaxial fatigue damage and in service biaxial thermal fatigue damage, a campaign has been conducted on a specific thermal fatigue device (SPLASH). The specimen is continuously heated by Joule effect and cyclically cooled by a water spray. To deduce the thermo-mechanical state of the specimen, two uncoupled computations are performed: a thermal analysis and a mechanical analysis with the previous computed temperature field as a given loading parameter. All the computations have been performed using the object-oriented finite element code cast3M. All the analysed tests show clearly that initiation under thermal fatigue occurs before initiation under uniaxial isothermal fatigue: thermal fatigue is the most damaging case. Such difference is not due to difference on microscopic mechanisms for that temperature range. It results from a pure mechanical origin: a biaxial state corresponds to an increase of the hydrostatic stress.
Characterising Residual Stresses in Rectangular Beam Specimens Following Thermo-Mechanical Loading
Authors: Mirzaee-Sisan Ali , Truman Christopher E. , Smith David J.
Published: July 2008

The neutron diffraction (ND) technique was used to characterise residual stress fields in thin rectangular beam specimens containing residual stresses induced thermo-mechanically by partial quenching. Two types of material were considered, type 316H stainless steel and A533B ferritic steel. The work was motivated by a need to investigate the influence of residual stress on the fracture behaviour of steels. During quenching, specimens experienced a severe temperature gradient which induced thermal stresses resulting in plastic strains and a subsequent residual stress field. An extensive finite element (FE) analysis was undertaken to predict the residual stress following thermo-mechanical loading. It was shown that partial quenching generated a considerable residual stress field in 316H stainless steel. However, the level of residual stresses in the A533B steel specimens was lower than that 316H stainless steel specimens. There was acceptable agreement between the finite element simulations and measurements with simulations generally predicting higher tensile residual stresses following partial quenching than those measured in the 316H stainless steel, and lower tensile residual stresses than those measured in the A533B ferritic steel.
Unified Basis-Free Relation Between Two Stress Tensors Conjugate to Arbitrary Hill’s Strain Measures
Authors: Asghari Mohsen , Naghdabadi Reza
Published: July 2008

The concept of energy conjugacy for stress and strain measures states that a stress tensor T is conjugate to a strain measure E if T: E˙ provides the rate of change of the internal energy per unit reference volume of the body in an adiabatic process. The applications of the conjugate stress and strain measures are in the development of the basic relations in nonlinear analysis of solids. In this paper using eigenprojection method, unified explicit basis-free relation between two arbitrary stress tensors T(f) and T(g), respectively conjugate to two measures of Hill’s strains is determined. The result is valid for arbitrary dimension of the Euclidean inner product space and for all cases of distinct and repeated eigenvalues of the right stretch tensor U.
Numerical Simulation of Dynamic Instability for a Pipe Conveying Fluid
Authors: Huvelin Fabien , Longatte Elisabeth , Verreman Vale´rie , Souli M’hamed
Published: July 2008

The present work is devoted to simulation of fluid-structure interaction and flow-induced vibration problems by using a partitioned procedure. A finite element structure solver is coupled with a finite volume fluid solver. A coupling interface has been developed for grid interpolation and scheme coupling control. An alternative mesh motion to a classical ALE formulation is proposed for the fluid computation and the method is validated by means of a test-case involving a pipe conveying fluid.
Preliminary Design of Vessels to Contain Explosions
Authors: Clayton Alan M.
Published: July 2008

Vessels containing explosions are used for weapons transport and disposal and for experimental studies of high shock loading on materials. This paper describes simple approaches to the initial outline design of such vessels, which would subsequently be confirmed and enhanced by detailed finite element work. Initial explosive pressure pulses are estimated and used to assess the breathing mode response of the vessel. Rule of thumb estimates are then obtained of other significant modes, and allowances made for features such as ports. The allowable levels of strain are set from a proposed code case for such loadings. An assessment is also made of the remaining static pressure after the shock has decayed. The methods allow rapid parametric studies and selection of materials.
An Efficient Meshfree Method for Fracture Analysis of Cracks in Bi-Materials
Authors: Nandulal B. , Rao B. N. , Lakshmana Rao C.
Published: July 2008

This paper presents an enriched meshless method based on an improved moving least-square approximation (IMLS) method for fracture analysis of cracks in homogeneous, isotropic, linear-elastic, two-dimensional bimaterial solids, subject to mixed-mode loading conditions. The method involves an element-free Galerkin formulation in conjunction with IMLS and a new enriched basis functions to capture the singularity field in linear-elastic bi-material fracture mechanics. In the IMLS method, the orthogonal function system with a weight function is used as the basis function. The IMLS has higher computational efficiency and precision than the MLS, and will not lead to an ill-conditioned system of equations. The proposed enriched basis function can be viewed as a generalized enriched basis function, which degenerates to a linear-elastic basis function when the bimaterial constant is zero. Numerical examples are presented to illustrate the computational efficiency and accuracy of the proposed method.
Optical Strain Gage Measurement of Accumulated Damage Around Geometrical Discontinuities Such as in Pipes and Pressure Vessels
Authors: Ranson William F. , Vachon Reginald I.
Published: July 2008

The optical strain gage technologies are used to measure strain and evaluate accumulated damage around a geometrical discontinuity such as holes, notches or fillets that exist in pipes and pressure vessels. Results are presented for coupons undergoing stress. The results are consistent with theory. The DMI technologies optically observe record and measure the deformation of a target affixed to the surface of the part undergoing stress in a region of expected maximum strain or a region physically and mathematically linked to the region of maximum strain. Data is acquired from its proprietary target (strain gage) or 2D Data Matrix mark used as a target/strain gage. The deformation of the mark/strain gage as the object undergoes deformation is mathematically described by total strain equal to the elastic and plastic strain components. This equation can be rewritten to express strain life in terms of plastic strain. The measured plastic component of strain is directly related to the damage.
Painting and Coating of Acoustic Materials
Authors: Burby M. , Nasr G. G. , Cox T.
Published: July 2008

Acoustic materials are used to treat indoor and outdoor spaces to make speech intelligible, and places less noisy and more pleasant to be in. Whilst most treatments are old and well established, in recent years there has been a growth in innovative products, which overcome difficulties with the old technologies, especially when making the treatments more visually acceptable to architects. Modern construction depends a great deal on acoustic materials to act as sound containment or sound control, either in residential or commercial applications. Sound-absorbing materials are highly porous to increase their sound absorption qualities. The amount of absorption depends on the thickness of the porous material, the size and number of pores, and the frequency of the noise. When painting acoustic materials, the painter should be very careful that the paint does not close up the acoustic surfaces; perforations or fissures. It is through these openings in the surface that sound waves enter the body of the acoustic material and are absorbed. It is the control of the paint droplet size upon the surface that affects the acoustic properties and the aesthetic appearance of the coated surface. An investigation into the coating performance with regard to acoustic absorption and aesthetic appearance was performed in a true-scale automotive spray booth using five different types of paint: three aerosol paints, domestic emulsion and acoustic paint. The sprays produced by the aerosols, emulsion and acoustic paints, applied using an air assist spray-gun, were characterised using a Mastersizer-X laser instrument. The flow rate of the paint through the spray gun was varied during the experiments between 50 ml/min and 500 ml/min. The work has highlighted the operating parameters for the air-assist spray gun in order to produce the smallest drop sizes. The measuring of the acoustic coefficient of the coated materials has shown that the aerosol and air-assist gun produced too large a droplet to produce a good acoustic coating. The use of the acoustic paint did create a good absorption coefficient but the work has highlighted the requirement for the atomizing process to be optimised for this highly viscous acoustic paint.
Optimisation of Weld Modelling Techniques: Bead-on-Plate Analysis
Authors: Dennis R. J. , Leggatt N. A. , Gregg A.
Published: July 2008

Finite element studies have been carried out simulating 3-dimensional deposition of weld metal on a flat plate. The purpose of this work is to further understand and develop the modelling requirements in order to accurately predict post weld residual stresses when compared to residual stress measurements. A single bead on plate specimen has been chosen as it has similar characteristics to those occurring in a repair weld which is of engineering interest. This analysis makes use of detailed fabrication records such as thermocouples, recorded heat inputs and etched macrographs which detail the fusion boundary profile. Analysis of the macrographs indicate a reduced weld penetration towards the end of the weld bead and especially along the centre-line of the bead where a “double-lobed” appearance was noted when viewed on a plane perpendicular to the bead. At the start position, a deeper fusion boundary was observed relative to the majority of the weld bead. The aim of this piece of work was to match the observed and predicted fusion boundaries and to analyse the influence on the predicted residual stresses when compared to a constant fusion boundary, along the length of the bead, as modelled in earlier analysis of the bead-on-plate. Two mechanical simulations were conducted based upon the matched fusion boundary thermal solution. These mechanical simulations utilised two hardening models, both of which are based on a non-linear kinematic hardening model but derived from different test data. A baseline kinematic hardening model has been used that is derived from monotonic and single pass weld bead specimens. A mixed hardening model has also been used which has been derived from both monotonic and cyclic test data. Furthermore this analysis takes advantage of some new features to weld modelling. In particular these include the Dynamic Fusion Boundary (DFB) approach where material properties are assigned to elements according to their temperature history.
Optimal Design of an Isotropic Porous-Cellular Cylindrical Shell
Authors: Magnucki Krzysztof , Malinowski Marek , Lewinski Jerzy
Published: July 2008

The paper outlines the effects on an isotropic porous-cellular cylindrical shell when subjected to a combined load: of axial force and external pressure. Metal porosity varies across the thickness of the shell wall. A dimensionless porosity parameter is introduced to compensate for this. Nonlinear hypothesis of deformation of the flat cross section of the shell wall is formulated. A system of five differential equations is defined on the basis of the theorem of the minimum of total potential energy. This system of equations is then analytically solved with Galerkin’s method. Critical loads for a family of porous shells are numerically determined based on the analytical solution. The optimization problem considers two criteria: minimum of mass and maximum of critical load on the shell. Optimal porosity variability for the cylindrical shell is determined numerically. An optimal dimensionless porosity parameter is then defined. Moreover, a comparative analysis for selected cylindrical shells with the use of FEM is performed. Results of the calculation are shown in respective figures. Finally, the results of the investigation for porous cylindrical shells are compared to the corresponding results for isotropic homogeneous shells.
Technical Advances of Chinese Standards for NDT of Pressure Equipment
Authors: Yuan Rong , Guan Weihe , Chen Wenhu , Fan Yu , Yan Changzhou , Chen Xuedong
Published: July 2008

JB4730-94 “pressure vessel NDT” is a compulsory Chinese industrial NDT standard for manufacture and erection of pressure vessel and pressure pipeline. Since more than 10 years from implementation of this standard, it has played a positive role in normalization of pressure vessel management, improvement of design, material selection, manufacture, use and inspection level of pressure vessel sector, reduction of explosion accidents, etc. In the year 2000, Chinese government decided to entrust us to revise JB4730, the revised JB4730-2005 “Pressure vessel NDT” is a backbone standard of Chinese pressure equipment sector. It defines the five major conventional inspection methods such as RT, UT, MT, PT and eddy-current inspection and qualification of quality class (it also defines the use of new NDT technology such as AE, real-time radiographic imaging, etc. in some special applications.) Because the number and use scope of Chinese domestic in-service pressure equipment have already reached a rather substantial scale and there is a lack of inspection standards, we added the content concerning the NDT of in-service pressure equipment. In order to meet the needs for macro-scale operations technology of equipment and wide application of corrosion resistant materials, we absorbed the research achievements on NDT of recent years, extended the application range of the standard, for example, we expanded the thickness range for RT of buttwelds to 2∼400mm; expanded the thickness range of UT to 6∼400mm; newly added the contents for NDT of the pressure equipment made of austenitic stainless steel, duplex stainless steel, nickel and nickel alloy, copper and copper alloy, aluminum and aluminum alloy and titanium and titanium alloy; added the content for UT of circumferential buttwelds on small-diameter thin-wall steel pipes. In this paper a systematic description is given to the main revision content and revision background of JB4730 standard, which has some directive significance for understanding and learning the present situation and development tendency of NDT of Chinese pressure equipment.
Failure Pressure for Steam Generator Tube With Two Different Collinear Axial Through-Wall Cracks
Authors: Huh Nam-Su , Chang Yoon-Suk , Kim Young-Jin
Published: July 2008

To maintain the structural integrity of steam generator tubes, 40% of wall thickness plugging criterion has been developed. The approach is for the steam generator tube with single crack, so that the interaction effect of multiple cracks can not be considered. Although, recently, several approaches has been proposed to assess the integrity of steam generator tube with two identical cracks whilst actual multiple cracks reveal more complex shape. In this paper, the failure pressure of steam generator tube containing multiple cracks of different length is evaluated based on the detailed 3-dimensional elastic-plastic finite element (FE) analyses. In terms of the crack shape, two collinear axial through-wall cracks with different length were considered. Furthermore, the resulting FE failure pressures are compared with FE failure pressures and experimental results for two identical collinear axial through-wall cracks to quantify the effect of crack length ratio on failure behavior of steam generator tube with multiple cracks.
Glycogen Synthase Kinase 3 Is a Potential Drug Target for African Trypanosomiasis Therapy
Authors: Ojo Kayode K. , Gillespie J. Robert , Riechers Aaron J. , Napuli Alberto J. , Verlinde Christophe L. M. J. , Buckner Frederick S. , Gelb Michael H. , Domostoj Mathias M. , Wells Susan J. , Scheer Alexander , Wells Timothy N. C. , Van Voorhis Wesley C.
Published: July 2008

Development of a safe, effective, and inexpensive therapy for African trypanosomiasis is an urgent priority. In this study, we evaluated the validity of
Trypanosoma brucei
glycogen synthase kinase 3 (GSK-3) as a potential drug target. Interference with the RNA of either of two GSK-3 homologues in bloodstream-form
T. brucei
parasites led to growth arrest and altered parasite morphology, demonstrating their requirement for cell survival. Since the growth arrest after RNA interference appeared to be more profound for
T. brucei
GSK-3 “short” (Tb10.161.3140) than for
T. brucei
GSK-3 “long” (Tb927.7.2420), we focused on
T. brucei
GSK-3 short for further studies.
T. brucei
GSK-3 short with an N-terminal maltose-binding protein fusion was cloned, expressed, and purified in a functional form. The potency of a GSK-3-focused inhibitor library against the recombinant enzyme of
T. brucei
GSK-3 short, as well as bloodstream-form parasites, was evaluated with the aim of determining if compounds that inhibit enzyme activity could also block the parasites' growth and proliferation. Among the compounds active against the cell, there was an excellent correlation between activity inhibiting the
T. brucei
GSK-3 short enzyme and the inhibition of
T. brucei
growth. Thus, there is reasonable genetic and chemical validation of GSK-3 short as a drug target for
T. brucei
. Finally, selective inhibition may be required for therapy targeting the GSK-3 enzyme, and a molecular model of the
T. brucei
GSK-3 short enzyme suggests that compounds that selectively inhibit
T. brucei
GSK-3 short over the human GSK-3 enzymes can be found.
Antimalarial Activity of Phenylthiazolyl-Bearing Hydroxamate-Based Histone Deacetylase Inhibitors
Authors: Dow Geoffrey S. , Chen Yufeng , Andrews Katherine T. , Caridha Diana , Gerena Lucia , Gettayacamin Montip , Johnson Jacob , Li Qigui , Melendez Victor , Obaldia Nicanor , Tran Thanh N. , Kozikowski Alan P.
Published: July 2008

The antimalarial activity and pharmacology of a series of phenylthiazolyl-bearing hydroxamate-based histone deacetylase inhibitors (HDACIs) was evaluated. In in vitro growth inhibition assays approximately 50 analogs were evaluated against four drug resistant strains of
Plasmodium falciparum
. The range of 50% inhibitory concentrations (IC
50
s) was 0.0005 to >1 μM. Five analogs exhibited IC
50
s of <3 nM, and three of these exhibited selectivity indices of >600. The most potent compound, WR301801 (YC-2-88) was shown to cause hyperacetylation of
P. falciparum
histones, which is a marker for HDAC inhibition in eukaryotic cells. The compound also inhibited malarial and mammalian HDAC activity in functional assays at low nanomolar concentrations. WR301801 did not exhibit cures in
P. berghei
-infected mice at oral doses as high as 640 mg/kg/day for 3 days or in
P. falciparum
-infected
Aotus lemurinus lemurinus
monkeys at oral doses of 32 mg/kg/day for 3 days, despite high relative bioavailability. The failure of monotherapy in mice may be due to a short half-life, since the compound was rapidly hydrolyzed to an inactive acid metabolite by loss of its hydroxamate group in vitro (half-life of 11 min in mouse microsomes) and in vivo (half-life in mice of 3.5 h after a single oral dose of 50 mg/kg). However, WR301801 exhibited cures in
P. berghei
-infected mice when combined at doses of 52 mg/kg/day orally with subcurative doses of chloroquine. Next-generation HDACIs with greater metabolic stability than WR301801 may be useful as antimalarials if combined appropriately with conventional antimalarial drugs.
Streptozocin-Induced Diabetic Mouse Model of Urinary Tract Infection
Authors: Rosen David A. , Hung Chia-Suei , Kline Kimberly A. , Hultgren Scott J.
Published: July 2008

Diabetics have a higher incidence of urinary tract infection (UTI), are infected with a broader range of uropathogens, and more commonly develop serious UTI sequelae than nondiabetics. To better study UTI in the diabetic host, we created and characterized a murine model of diabetic UTI using the pancreatic islet β-cell toxin streptozocin in C3H/HeN, C3H/HeJ, and C57BL/6 mouse backgrounds. Intraperitoneal injections of streptozocin were used to initiate diabetes in healthy mouse backgrounds, as defined by consecutive blood glucose levels of >250 mg/dl. UTIs caused by uropathogenic
Escherichia coli
(UTI89),
Klebsiella pneumoniae
(TOP52 1721), and
Enterococcus faecalis
(0852) were studied, and diabetic mice were found to be considerably more susceptible to infection. All three uropathogens produced significantly higher bladder and kidney titers than buffer-treated controls. Uropathogens did not have as large an advantage in the Toll-like receptor 4-defective C3H/HeJ diabetic mouse, arguing that the dramatic increase in colonization seen in C3H/HeN diabetic mice may partially be due to diabetic-induced defects in innate immunity. Competition experiments demonstrated that
E. coli
had a significant advantage over
K. pneumoniae
in the bladders of healthy mice and less of an advantage in diabetic bladders. In the kidneys,
K. pneumoniae
outcompeted
E. coli
in healthy mice but in diabetic mice
E. coli
outcompeted
K. pneumoniae
and caused severe pyelonephritis. Diabetic kidneys contained renal tubules laden with communities of
E. coli
UTI89 bacteria within an extracellular-matrix material. Diabetic mice also had glucosuria, which may enhance bacterial replication in the urinary tract. These data support that this murine diabetic UTI model is consistent with known characteristics of human diabetic UTI and can provide a powerful tool for dissecting this infection in the multifactorial setting of diabetes.
Adaptation of
Francisella tularensis
to the Mammalian Environment Is Governed by Cues Which Can Be Mimicked In Vitro
Authors: Hazlett Karsten R. O. , Caldon Seth D. , McArthur Debbie G. , Cirillo Kerry A. , Kirimanjeswara Girish S. , Magguilli Micheal L. , Malik Meenakshi , Shah Aaloki , Broderick Scott , Golovliov Igor , Metzger Dennis W. , Rajan Krishna , Sellati Timothy J. , Loegering Daniel J.
Published: July 2008

The intracellular bacterium
Francisella tularensis
survives in mammals, arthropods, and freshwater amoeba. It was previously established that the conventional media used for in vitro propagation of this microbe do not yield bacteria that mimic those harvested from infected mammals; whether these in vitro-cultivated bacteria resemble arthropod- or amoeba-adapted
Francisella
is unknown. As a foundation for our goal of identifying
F. tularensis
outer membrane proteins which are expressed during mammalian infection, we first sought to identify in vitro cultivation conditions that induce the bacterium's infection-derived phenotype. We compared
Francisella
LVS grown in brain heart infusion broth (BHI; a standard microbiological medium rarely used in
Francisella
research) to that grown in Mueller-Hinton broth (MHB; the most widely used
F. tularensis
medium, used here as a negative control) and macrophages (a natural host cell, used here as a positive control). BHI- and macrophage-grown
F. tularensis
cells showed similar expression of MglA-dependent and MglA-independent proteins; expression of the MglA-dependent proteins was repressed by the supraphysiological levels of free amino acids present in MHB. We observed that during macrophage infection, protein expression by intracellular bacteria differed from that by extracellular bacteria; BHI-grown bacteria mirrored the latter, while MHB-grown bacteria resembled neither. Naïve macrophages responding to BHI- and macrophage-grown bacteria produced markedly lower levels of proinflammatory mediators than those in cells exposed to MHB-grown bacteria. In contrast to MHB-grown bacteria, BHI-grown bacteria showed minimal delay during intracellular replication. Cumulatively, our findings provide compelling evidence that growth in BHI yields bacteria which recapitulate the phenotype of
Francisella
organisms that have emerged from macrophages.
Anti-Inflammatory Mechanisms of EntericHeligmosomoides polygyrusInfection against Trinitrobenzene Sulfonic Acid-Induced Colitis in a Murine Model
Authors: Sutton Thomas L. , Zhao Aiping , Madden Kathleen B. , Elfrey Justin E. , Tuft Blaine A. , Sullivan Carolyn A. , Urban Joseph F. , Shea-Donohue Terez
Published: July 2008

Recent studies showed that enteric helminth infection improved symptoms in patients with inflammatory bowel disease as well as in experimental models of colitis. The aim of this study was to determine the mechanism of the protective effect of helminth infection on colitis-induced changes in immune and epithelial cell function. BALB/c mice received an oral infection ofHeligmosomoides polygyrusthird-stage larvae, were given intrarectal saline or trinitrobenzene sulfonic acid (TNBS) on day 10 postinfection, and were studied 4 days later. Separate groups of mice received intrarectal saline or TNBS on day 10 and were studied on day 14. Muscle-free colonic mucosae were mounted in Ussing chambers to measure mucosal permeability and secretion. Expression of cytokines was assessed by quantitative real-time PCR, and mast cells were visualized by immunohistochemistry. TNBS-induced colitis induced mucosal damage, upregulated Th1 cytokines, and depressed secretory responses.Heligmosomoides polygyruselevated Th2 cytokine expression, increased mast cell infiltration and mucosal resistance, and also reduced some secretory responses. PriorH. polygyrusinfection prevented TNBS-induced upregulation of Th1 cytokines and normalized secretory responses to specific agonists. TNBS-induced colitis did not alterH. polygyrus-induced mast cell infiltration or upregulation of Th2 cytokine expression. The results indicate that the protective mechanism of enteric nematode infection against TNBS-induced colitis involves prevention of Th1 cytokine expression and improved colonic function by a mechanism that may involve mast cell-mediated protection of neural control of secretory function. Similar response patterns could account for the clinical improvement seen in inflammatory bowel disease with helminthic therapy.
A Theoretical and Experimental Investigation of Mildly Nonlinear Consolidation Behavior in Saturated Soil
Authors: Poskitt T. J. , Birdsall R. O.
Published: July 2008

A theory is given which enables variable permeability and compressibility, large strain, and non-Newtonian viscous effects in the soil skeleton to be considered in the one-dimensional consolidation of saturated soil. The first three of these are fairly well understood phenomena and their influence on field behavior is predictable. The last, however, is much more open to interpretation and has been included to cover laboratory testing of thin samples where viscous effects are often known to be important. The rheological model used for the soil skeleton is of the same general form as that used by Gibson and Lo in their investigation of linear behavior in clays. However, in the present case nonlinear physical laws of a form known to fit the experimental data more closely have been used. This makes the governing equations nonlinear and they are correspondingly more difficult to solve. The principal theoretical results for settlement and pore pressure are given in a form convenient for practical use and a procedure is given whereby the basic soil parameters can be determined from a laboratory settlement curve. By using the parameters so obtained the theoretical midplane pore pressure can be computed and when compared with the experimental curve this gives a stringent test of the adequacy of the theory. Experimental results for three different clays are given, and the theory shows encouraging agreement with these.
Natural Slope Failure, Northeastern Skeena Mountains
Authors: Eisbacher G. H.
Published: July 2008

Twenty-five rockslides in sedimentary strata of the Skeena Mountains in north-central British Columbia are concentrated along a distinct belt approximately 30 km wide. Four slides belong to a "shallow" type, 21 to a "deep" slide type. Regional structural trend, deformation, and lithological heterogeneity seem to control distribution and direction of slip of these rockslides. Slopes oriented parallel to the structural trend and made up of heterogeneous conglomerate, sandstone, shale successions are more likely to fail than others.
A Bubbler–Manometer Water Level Sensing and Recording System
Authors: Morrison B. , Meneley W. A.
Published: July 2008

A bubbler–manometer water level sensing and recording system for observation wells and stream stage hydrometric stations has produced continuous hydrographs (continuity >90%) throughout winter and summer seasons on an observation well and a hydrometric station. The system utilizes a conventional float-type recorder which operates unattended for a 30-day period. No external energy source is required and the system functions over 100 days on a 224 ft3 (6.34 m3) bottle of nitrogen. A protective housing is an integral part of the installation so that the instrument can be safely installed wherever required and will operate throughout the winter without requiring any heating. These features, combined with simplicity of construction and functional durability, makes this design economically attractive for many locations where it is not possible to sense water level changes directly with a float-operated recorder.
Stress Distribution in Rock Anchors
Authors: Hollingshead Garry W.
Published: July 2008

A finite element method is employed to analyze the stress distribution along a steel anchor bolt grouted into rock. Penetration of the yielded zone into the grout wall and redistribution of stresses with increasing load are illustrated. The effect of varying modular ratio in a two-material system subjected to tensile loads is also illustrated.
Land Subsidence in Built-up Marshland
Authors: Bozozuk M. , Penner E.
Published: July 2008

Severe land subsidence has been observed in a residential area in Ottawa built some 15 to 20 years ago on marshland. Subsidence varies from 12 to 18 in. (30 to 45 cm), affecting streets, sidewalks, driveways, fences, garages, and other structures supported on the ground surface. Houses were not affected because they were founded on shallow bedrock. Accelerated decomposition of the peat and the underlying marl is believed to have started when the area was drained for development, and this is believed to be responsible for the severe subsidence observed.
Analysis of a Failed Slope
Authors: Thomson S.
Published: July 2008

In September 1963, a landslide occurred in Upper Cretaceous clay shales of Western Canada. An analysis indicated that peak strengths were being mobilized on the steeply dipping portion of the slip surface and that strengths less than peak but greater than residual were acting along the lower part of the failure surface.In March 1971, a stadia profile of the failed slope was obtained and analyzed. In the 7.5-year interval, movement increased the scarp height from 22 to 34 ft (7–10 m). The results of the analysis indicate that the cohesion parameter has tended to zero and that the friction angle has decreased toward a residual value, at least along a part of the failure surface.
Deformation Characterization of Subgrade Soils for Highways and Runways in Northern Environments
Authors: Fredlund D. G. , Bergan A. T. , Sauer E. K.
Published: July 2008

Roads and runways in Northern Canada often must carry exceptionally heavy loads. In order to design for these loads, a procedure has been developed which enables the prediction of fatigue life of pavements. Experimental evidence indicates that the definition of resilient deformation, which controls fatigue life of pavements, can be resolved in terms of stress state variables. The resilient modulus is defined in terms of (σ1 – σ3), (σ3 – ua), and (ua – uw) which is applied in a theoretical analysis. Typical forms of the constitutive relationships are presented. The effect of freeze–thaw cycles does not appear to produce significant hysteresis in the constitutive relationships.
Electroosmotic Reduction of Ocean Bottom Breakout Forces and Times
Authors: Roderick G. L.
Published: July 2008

Laboratory model pullout tests were conducted with a cylindrical object, 1 sediment, 1 object in situ time, 3 electrode configurations, and electric potential gradients of 0, 0.25, and 0.5 V/cm to determine the effect of electroosmosis on reducing force and time requirements for breaking objects free of soft sediments.Results show electroosmosis to be very effective in reducing breakout times. The relationship between the breakout force ratio and breakout time can be expressed in terms of 2 empirical parameters. Electrical power requirements to achieve breakout appear to be independent of electrode configurations but do depend on electric potential gradients.
Innovations in Tailings Disposal
Authors: Shields Donald Hugh
Published: July 2008

Traditional methods of mine tailings disposal are shown to compromise public safety and protection of the environment. Two designs are described which more closely meet these concerns. They represent a departure from the traditional methods and should stimulate a re-appraisal of previously held concepts of tailings disposal.
Hydrogeologic Investigation of a Radioactive Waste Management Site in Southern Alberta
Authors: Schwartz Franklin W.
Published: July 2008

For the past 2 years, detailed field and laboratory studies have focused on the hydrogeologic investigation of a proposed, subsurface, radioactive waste management site in Alberta at the Defence Research Establishment Suffield. The basic approach has involved test drilling and sampling augmented by down-hole geophysical techniques to establish stratigraphic sequences. In addition, piezometers and soil moisture – temperature blocks have been emplaced to define the saturated–unsaturated flow regime. Laboratory studies of drift and bedrock samples have characterized variations in mineralogy, texture, and sorptive properties.Piezometric data indicate that the site is predominantly a recharge area with median values of permeability ranging from 2.8 × 10−2 to 2.8 × 10−4 ft/day (1 × 10−5 to 1 × 10−7 cm/s). To reach the zone of saturation, recharge water must pass downward through a maximum of 120 ft (36.3 m) of unsaturated, glacial drift with cation exchange capacities ranging from 25 to 105 mequiv per 100 g. The absence of water level fluctuations in observation wells and the soil moisture block data indicate that the quantity of water moving downward through the waste management site is small.
Bearing Capacity of Strip Footings in Frozen Soils
Authors: Ladanyi B.
Published: July 2008

The first part of this paper discusses some basic requirements for the determination of the allowable bearing pressure for frozen soils, with a particular reference to the delayed deformations due to creep and consolidation, which occur simultaneously in frozen soils containing large amounts of unfrozen water.In the second part of the paper, it is shown how the creep settlement and failure of a strip footing in frozen soil can be predicted by using a simple mathematical model of an expanding cylindrical cavity. With the help of a previously obtained solution, valid for a circular footing, and an appropriate empirical depth factor, the present solution is then extended to cover also the bearing capacity of footings of any shape and at any depth of embedment.