bluuebunny/crossref_metadata_2025 huggingface dataset:
Compressive Strength and Failure Modes of Unidirectional Composites
Authors: Greszczuk LB
Published: March 2009

Experimental and theoretical studies are presented on the failuremodes of unidirectional composites subjected to compressive loading parallel to the fiber direction. The various theories which predict microbuckling as a failure mode in compression are reviewed and compared. Nearly perfect model composites consisting of circular rods in an epoxy matrix are employed to obtain experimental data. Compression test data, including different failur modes, are obtained for composites made with brittle, anisotropic fibers and with ductile, isotropic fibers imbedded in matrix materials with Young's moduli ranging from 2 to 460 ksi. Test variables investigated include specimen geometry, fiber diameter, fiber volume fraction, and properties of constituents. It is found that all of the just mentioned parameters influence the compressive microbuckling strength. Moreover, the properties of constituents influence the modes of failure in compression. Elastic and inelastic micro-buckling is found in composites made with low- and intermediate-moduli resins and ductile fibers. For ductile fiber-rigid resin composites, the failure is by compression yielding of the reinforcement. For composites reinforced with anisotropic graphite fibers there exist three different compression failure modes: (1) microbuckling in the shear mode in the case of composites made with low modulus resin; (2) transverse tension failure, including fiber “splitting,” in the case of composites made with intermediate modulus resin; and (3) compression failure of the reinforcement in the case of composites made with high modulus resin. The test results are compared with theoretical predictions.
Isotopic Abundance Determination of Submicro Amounts of Rhenium by Neutron Activation
Authors: Michel R , Herpers U , Kulus H , Herr W
Published: March 2009

Neutron activation is applied to the isotopic abundance measurements of rhenium in lunar matter. This is achieved by comparing the (n, γ) induced activities of 1 8 6Re and 1 8 8Re by the 137 keV and the 155 keV γ-line, respectively. Radiochemical processing to a very high purity is needed in order to avoid interferences of 1 9 9Au and 9 9 mTc. Additionally, the rhenium and tungsten contents were determined.

An isotopic anomaly of rhenium was established in Apollo 14 samples, exhibiting a remarkable enrichment of 1 8 7Re (1.4 to 1.8 percent in soils and up to 29 percent in the breccia 14321). It is shown that this enrichment is at least partially due to neutron irradiation on the lunar surface by the reaction 1 8 6W(n, γ) 1 8 7W β→ 1 8 7Re. However, the observed anomaly is not produced by lunar neutrons alone. There is also a contribution from the reaction 1 8 6W(n, γ) 1 8 7W β→ 1 8 7Re (n, γ) 1 8 8Re in the reactor itself which can be corrected for by the analysis of simultaneously irradiated tungsten standards. The lunar #x201C;share#x201D; of the 1 8 7Re enrichment is found to be 20 to 60 percent of the observed total excess. It is shown that the 1 8 6W neutron capture is mainly due to epithermal neutrons (resonances are at 18.8, 171, and 221 eV). Relationships to the recently discovered other neutron induced isotope anomalies in extraterrestrial matter are discussed, and the possibility of deriving neutron spectra and time integrated neutron fluxes is pointed up.
Fatigue at Elevated Temperatures: A Review of Test Methods
Authors: Carden AE
Published: March 2009

The study of fatigue at elevated temperature requires the evaluation of material response to several load-time profiles in specified thermal-chemical-nuclear-electric fields. This review of test methods emphasizes the relationships between “pure low-cycle fatigue” and tensile, fracture toughness, creep, cyclic-creep, creep fatigue (interspersion), fatigue-cycle-with-hold, dynamic creep, fatigue crack growth, and high-cycle fatigue testing. The thermal and environmental control is discussed. Special attention is given to isothermal-uniaxial, bending, torsion, and combined stress tests. Cyclic thermal testing is reviewed. Strain measurement, signal conditioning, computer utilization, fatigue crack growth, vacuum and environmental control, nondestructive testing, acoustic emission, and fractography are reviewed as they pertain to fatigue at elevated temperature. Specimen design, gripping, and testing machine characteristics are also discussed.
Combined Low-Cycle Fatigue and Stress Relaxation of Alloy 800 and Type 304 Stainless Steel at Elevated Temperatures
Authors: Jaske CE , Mindlin H , Perrin JS
Published: March 2009

A detailed analysis was made of data from low-cycle fatigue tests of solution-annealed, nickel-iron-chromium Alloy 800 at 1000, 1200, and 1400 F and of Type 304 austenitic stainless steel at 1000 and 1200 F with holdtimes at maximum tensile strain. A single equation was found to approximate the cyclically stable stress relaxation curves for both alloys at these temperatures. This equation was then used in making a linear time fraction creep damage analysis of the stable stress relaxation curves, and a linear life fraction rule was used to compute fatigue damage. Creep-fatigue damage interaction was evaluated for both alloys using the results of these damage computations. Strain range was found to affect the damage interaction for Type 304 stainless steel but not for the Alloy 800. With increasing holdtime, both creep and total damage increased for the Alloy 800 and decreased for the Type 304 stainless steel, and fatigue damage decreased for both alloys. A method was developed to relate length of holdtime and fatigue life to total strain range. This method provides a simple and reasonable way of predicting fatigue life when tensile holdtimes are present.
Combined Creep-Fatigue Behavior of Inconel Alloy X-750
Authors: Venkiteswaran PK , Ferguson DC , Taplin DMR
Published: March 2009

A study has been made of the effect of superimposing a small lateral vibratory stress on the axial creep behavior of Inconel Alloy X-750 at 700 C. Tests were conducted in a specially designed creep-fatigue testing machine using specimens simulating gas turbine blades. From preliminary data in combined creep-fatigue, it was found that the creep rate was lower and rupture life higher by almost an order of magnitude compared to the creep values. Fracture mode in combined creep-fatigue was a mixture of intergranular, fatigue, and cleavage. It was also observed that the cleavage fracture was “bowed out” or serrated indicating that the intragranular γ/precipitates arrest the propagation of cracks. This and the change in fracture mode could be responsible for the lower creep rates and longer rupture lives. There was no evidence of grain boundary migration, change in grain size, or formation of “diamond” grains.
Skid Resistance of Epoxy Asphalt Pavements On California Toll Bridges
Authors: Seim C
Published: March 2009

The California State Division of Bay Toll Crossings has used dense graded epoxy asphalt pavement for surfacing two orthotropic steel deck bridges and open graded epoxy asphalt pavement for restoring the skid resistance of a deteriorated epoxy coal tar chip seal placed on a concrete bridge. It has proved to be durable, withstanding repetitive flexure, and providing good skid resistance when placed on steel decks. It also has proved to be a durable and skid resistant pavement when placed on a concrete deck as thin as ½ in. to limit induced dead load stresses. The thermosetting epoxy asphalt binder will not flush to the surface and holds the aggregate with a strong bond that allows full exposure of the particle faces. Aggregate that provides high fatigue life for orthotropic steel decks will probably produce high skid resistance. Sixteen test sections of pavement were placed in late 1971 for skid resistance evaluations. Six of these are dense graded epoxy asphalt pavements. The results to date indicate good durability and good skid resistance. Graphs of variation of skid number with time are presented for twelve epoxy asphalt pavements.
Study of the Skid Resistance of Different Tire Tread Polymers on Wet Pavements with a Range of Surface Textures
Authors: Lupton GN , Williams T
Published: March 2009

As part of the British Transport and Road Research Laboratory's research program to determine the relative magnitude of the various factors influencing grip on wet pavements, measurements of skid resistance (braking force coefficient (BFC)) have been made using trailer and front wheel braking techniques.

The five sets of smooth treaded tires differed only in the tread polymers which were chosen to cover a range of physical properties. The tires were tested at speeds ranging from 1 km/h (0.5 mph) to 160 km/h (100 mph) on eight surfaces having a wide range of textures.

Macrotexture was measured by sandpatch “texture depth” and stereophotogrammetric “profile ratio” techniques. Comparison of the mean BFC/speed curves for each polymer shows a similarity of speed dependence, indicating that on the highway penetration of the water film is the overriding factor rather than a speed dependent viscoelastic effect which has been postulated from laboratory friction measurements.

However the order of the BFC shows evidence of viscoelastic behavior, the more resilient polymers giving the lower values. A hypothesis relating to a change in the tire/pavement contact conditions at high speeds is put forward that the high values of BFC on surfaces with large texture depth are partly due to modification of the contact conditions by changes in the viscosity of the lubricant brought about by heating.
Fracture Toughness Evaluation by R-Curve Methods
Authors: McCabe DE
Published: March 2009

Description

This publication is a collection of papers presented at a technical symposium on R-curves held during the regular Committee E24 meetings in the Fall of 1971. It represents an early effort by a Subcommittee 1 task group to organize the present state of R-curve technology in preparation for a renewed attempt to apply the method to plane-stress fracture toughness evaluation. The symposium was sponsored by Committee E24 on Fracture Testing of Metals, American Society for Testing and Materials. D. E. McCabe, Armco Steel Corp., presided as symposium chairman.
Rapid Methods for Chemical Analysis of Hydraulic Cement
Authors: Gebhardt RF
Published: March 2009

Description

Presents many of the rapid methods used successfully for analysis of hydraulic cements – the major component in concrete. Several consider the impact of ASTM C917, Method for Evaluation of Cement Strength Uniformity From a Single Source, and suggest that it is a (suitable yardstick to assess whether quality control procedures exercised are effective.)
Nonlinear Fracture Mechanics: Volume I Time-Dependent Fracture
Authors: Saxena A , Landes JD , Bassani JL
Published: March 2009

Description

Two volume set: Volume 1 -- Nonlinear Fracture Mechanics: Time Dependent Fracture. Volume 2 -- Nonlinear Fracture Mechanics: Elastic-Plastic Fracture

STP 995 contains recent work on traditional elastic plastic fracture mechanics as well newer areas, such as time dependent fracture mechanics and dynamic fracture. Papers discuss analytical considerations, experimental methods, and applications. Third in a series of ASTM books on nonlinear fracture mechanics.
Training Mental Health Professionals to Assess and Manage Suicidal Behavior: Can Provider Confidence and Practice Behaviors be Altered?
Authors: Oordt Mark S. , Jobes David A. , Fonseca Vincent P. , Schmidt Steven M.
Published: March 2009

Remarkably little systematic research has studied the effects of clinical suicidology training on changing practitioner attitudes and behaviors. In the current study we investigated whether training in an empirically‐based assessment and treatment approach to suicidal patients administered through a continuing education workshop could meaningfully impact professional practices, clinic policy, clinician confidence, and beliefs posttraining and 6 months later. At the 6 month follow‐up we found that 44% of practitioners reported increased confidence in assessing suicide risk, 54% reported increased confidence in managing suicidal patients, 83% reported changing suicide care practices, and 66% reported changing clinic policy. These results suggest that a brief and carefully developed workshop training experience can potentially change provider perceptions and behaviors with a possible impact on clinical care therein.
Declining Recruitment and Growth of Shovelnose Sturgeon in the Middle Mississippi River: Implications for Conservation
Authors: Tripp Sara J. , Colombo Robert E. , Garvey James E.
Published: March 2009

To determine how populations of shovelnose sturgeon Scaphirhynchus platorynchus are changing and may respond to poor environmental conditions, current commercial harvest of black‐egg (sexually mature) females, and incidental mortality of males, we require annual information about sex‐specific age structure as it relates to the recruitment of new cohorts. We sampled shovelnose sturgeon by use of gill nets (5‐cm bar mesh) monthly during 2002‐2006 in the Middle Mississippi River between Cairo, Illinois, and St. Louis, Missouri. We compared patterns of size and age structure over time and projected age structure and population size into the future. Sex ratio in 2005‐2006 was 1.14:1.00 (416 males and 363 females; P = 0.06), deviating from the 1:1 ratio that occurred in 2002‐2003. Annual mortality increased from 37% in 2002‐2003 to 44% by 2005‐2006. Female shovelnose sturgeon were larger than males. Across years, the population shifted toward longer, older fish, and growth in length declined. Recruitment declined through time (29% per year). If these trends continue and if immigration from nonharvested populations is limited, population density may decline by an order of magnitude within one decade. Under current conditions, resilience to harvest and environmental perturbations is probably limited.
A new approach for assessing geothermal response to climate change in permafrost regions
Authors: Nishimura S. , Martin C. J. , Jardine R. J. , Fenton C. H.
Published: March 2009

Infrastructure in cold regions is vulnerable to the potential degradation of permafrost under a warming climate. Meanwhile, the accumulation of meteorological data and the refinement of AOGCMs in recent years have improved the confidence in future global air temperature predictions. A reliable scheme is now desired that converts these climate predictions into future geocryological predictions relevant to geotechnical engineering and risk assessment. This paper describes a multidisciplinary approach that provides a first estimate of transient ground responses to climate change on a regional basis. The scheme integrates locally adjusted AOGCM climate predictions, regional geological assessments, non-linear thermal finite element analysis and digital elevation models derived from remote sensing data. The practical application of the approach is demonstrated through predictions made of the geocryological changes expected between 1940 and 2059 in a Siberian region. The paper presents results from one sampled area where discontinuous permafrost is present beneath rolling hills terrain. It is shown that elevation, vegetation and local geological variations all affect the development of permafrost, with important implications for infrastructure design and operation. A range of useful geocryological maps can be output from the procedure, including temperature at the active layer base, permafrost table depth, and ground temperature at any desired depth. It is shown that the permafrost model's predictions for present-day conditions agree well with existing geocryological maps. An illustrative example of how simple geohazard maps may be prepared from the output is also provided.
Inclusion of higher-temperature effects in a soil behaviour model
Authors: Thomas H. R. , Siddiqua S. , Seetharam S. C.
Published: March 2009

This technical note presents a coupled thermo-hydro-mechanical model for unsaturated soil, which can be applied in the context of high temperature. A new pore gas or bulk air transfer equation is introduced. Additionally the effect of temperature on the latent heat of vapourisation and specific heat capacities is incorporated. Adsorbed water is also included. The performance of the model is demonstrated via the simulation of a high temperature (150°C) thermo-hydraulic-mechanical experiment carried out on a column of MX-80 bentonite by Commissarait à l'Energie Atomique, France. The model showed good correlation of experimental and numerical results.
Use of energy piles in a residential building, and effects on ground temperature and heat pump efficiency
Authors: Wood C. J. , Liu H. , Riffat S. B.
Published: March 2009

Piled foundations for residential buildings have predominantly been used in areas where conventional trench footing foundations have not been possible. The reasons for this have included loose and unstable overburden and contaminated ground, which result in the use of concrete piles as an economically technical solution. More recent methods have enabled concrete pile foundations to become an economic option for ground conditions that would be otherwise considered for trench-fill. It is also realised that the heat load of modern residential buildings has reduced significantly in recent years, and will fall further in forthcoming years. It is now considered that the residential energy piles can not only be economically installed, but can also provide the necessary heat requirement, which is sustainable over the life of the building. A test plot has been produced with 21 concrete piles, 10 m deep, with a single U-tube pipe in each. A heat rejection facility was devised to simulate the heat load of a two-storey, modern residential building with ground floor area 72 m2. Testing of the energy piles has been conducted over the 2007–2008 heating season. The ground was monitored by thermocouples at depth along each pile, and also as an array at various depths and distances in the ground around the plot. The temperature variation of the ground and its effect upon the heat pump efficiency have been observed. Findings of the testing conducted over the 2007–2008 heating season are presented and analysed in this technical note.
Acidogenic Potential of “Sugar-Free” Cough Drops
Authors: Mayo John A , Ritchie John R
Published: March 2009

A patient presented with extensive marginal ditching around restorations recently placed during whole-mouth rehabilitation. The patient was not xerostomic and was otherwise normal except for the self-reported excessive use of “sugar-free” cough drops sweetened with sorbitol and Isomalt® (an equimolar mix of glucosyl-mannitol and glucosylsorbitol). This prompted anin vitroinvestigation to determine whetherStreptococcus sobrinus6715, a cariogenic streptococcus, could grow and produce acid in growth medium containing an aqueous extract of such “sugar-free” cough drops. The results indicate thatS. sobrinus6715 uses Isomalt® and sorbitol extensively, producing terminal culture pH as low as 4.2 when grown on medium with cough drop extract containing these sugars. This pH is sufficient to demineralize dental enamel. Patients should be cautioned against the chronic overuse of “sugar-free” cough drops and other “sugar-free” confections sweetened with a mixture of Isomalt® and sorbitol.
Mimesis and Mimicry in Dynamics of State and Identity Formation in Northern Somalia
Authors: Hoehne Markus V.
Published: March 2009

In this article, mimesis and mimicry are used as analytical concepts to explore dynamics of state and identity formation in Somaliland and Puntland since the early 1990s. Mimesis captures endeavours to imitate well-established models of social and political organization. Mimicry involves the deceptive imitation of such models in order to reach a certain aim. In the particular setting of northern Somalia, miming and mimicking in state and identity formation are also related to conflict escalation. The article first presents relevant political and legal positions on state collapse and secession. This helps to grasp the theoretical and policy implications of the empirical material. Then, the establishment of Somaliland and Puntland through mimesis and mimicry is sketched. The outline of the repeated military confrontations between both sides, particularly the last round of fighting in and around the town of Laascaanood in late 2007, indicates the relation of state and identity formation to military conflict. These localized dynamics are embedded into the continuing conflict in southern Somalia that involves a number of internal and external actors. The article concludes that miming and mimicking underlie many of Somaliland's and Puntland's internal developments and their conflictive relationship. Moreover, since the conflict in northern Somalia concerns state formation, it might have far-reaching consequences for the future of Somalia as a whole. This finally leads to the suggestion that the international norms regarding state collapse and secession have to be re-evaluated in the light of the empirical realities at hand.
Electric Power Distribution and Control for Subsea Field Development
Authors: Reetmeyer H.G. , Guenther S.K. , Just H.E.
Published: March 2009

The European offshore industry is encountering a significant change of thescenario. The necessity has come up to move from production of large fields inshallow water to many small and isolated fields in deeper water, thus requiringa higher degree of automation, higher availability, and lower cost (both subseaand on platforms). Therefore a control and power supply concept is described, which consequently introduces elements of modern automation technology tosubsea installations.

Starting Point

The situation in European oil and gas production is full of challenges bothin the engineering and commercial area.

We do have significant resources and production from our own (by far not bigenough to be autonomous, yet important at least from a political point ofview), but–distributed over many different regions,–not many big fields,–mostly offshore,–in many cases already beyond peak production rate.

The perspectives also are full of question marks, as–no big fields are to be expected in the future,–work has to concentrate on a wealth of small fields,–the fields will be offshore,–these small fields may be isolated (i.e. apart from existinginfrastructure),–water depth will increase (up to 600 m),–geographical latitude will increase (north of 62°)–the environment will become more and more hostile and pollutionsensitive,–the oil price is expected not to change significantly within the nextdecade.
M2 Macrophages Phagocytose Rituximab-Opsonized Leukemic Targets More Efficiently than M1 Cells In Vitro
Authors: Leidi Marzia , Gotti Elisa , Bologna Luca , Miranda Elena , Rimoldi Monica , Sica Antonio , Roncalli Massimo , Palumbo Giuseppe A. , Introna Martino , Golay Josée
Published: March 2009

Because macrophages have been implicated as major players in the mechanism of action of rituximab, we have investigated the factors that modulate their tumor cell killing potential. Human macrophages, differentiated in vitro from peripheral blood monocytes, were used in binding and phagocytosis assays using B-chronic lymphocytic leukemia or lymphoma target cells opsonized with rituximab. Phagocytosis was maximal at 0.1 μg/ml rituximab and was not significantly affected by CD20 expression levels or by CD16A polymorphism at position 158 (Val/Phe). The role of FcγRs was demonstrated by complete inhibition of phagocytosis by excess human Igs. Because macrophages can be differentiated to M1- or M2-type cells with either GM-CSF or M-CSF, respectively, and can be classically activated by proinflammatory stimuli (IFN-γ/LPS) or undergo alternative activation with cytokines such as IL-4 or IL-10, we have analyzed the effect of these different polarization programs on the phagocytosis mediated by rituximab. Macrophages differentiated in presence of M-CSF showed a 2- to 3-fold greater phagocytic capacity compared with GM-CSF-induced cells. Furthermore, addition of IL-10 significantly increased, whereas IL-4 decreased phagocytosis by both M-CSF- and GM-CSF-differentiated macrophages. LPS/IFN-γ had little effect. Expression of CD16, CD32, and CD64 in different macrophage populations correlated with phagocytic activity. Interestingly, several B lymphoma cell lines were observed to secrete 400-1300 pg/ml IL-10 in vitro, and coculture of human macrophages with lymphoma conditioned medium increased significantly their phagocytic capacity. Our data suggest that cytokines secreted by lymphoma cells can favor alternate activation of macrophages with a high phagocytic capacity toward rituximab-opsonized targets.
A Novel Peptide Mimotope Identified As a Potential Immunosuppressive Vaccine for Organ Transplantation
Authors: Chiang Kuei-Chen , Shimada Yayoi , Nakano Toshiaki , Lai Chia-Yun , Hsu Li-Wen , Goto Shigeru , Ohmori Naoya , Mori Kenji , Miyagi Takamitsu , Kawamoto Seiji , Ono Kazuhisa , Chen Chao-Long , Goto Takeshi , Sato Shuji
Published: March 2009

We reported that anti-histone H1 autoantibody is one of the main immunosuppressive factors in serum that is induced after orthotopic liver transplantation in a rat tolerogenic model. We generated a novel anti-histone H1 IgM mAb produced by hybridoma 16G9 (16G9 mAb) that shows MLR-inhibitory activity. Identification of a functional epitope responsible for the immunosuppressive activity of 16G9 mAb may lead to the establishment of a novel therapeutic strategy. We used a combinatorial phage display peptide library to screen for peptides that bind to 16G9 mAb. Consequently, two peptides that bind to 16G9 mAb, SSV and LPQ, were selected from the library. The binding of 16G9 mAb to histone H1 was inhibited by SSV. SSV was recognized by rat tolerogenic post-orthotopic liver transplantation serum and the binding to SSV was inhibited by histone H1. Mice were immunized with keyhole limpet hemocyanin-conjugated SSV and LPQ. Abs induced by SSV immunization inhibited Con A-stimulated splenocyte proliferation, and the inhibition was neutralized by preincubation with SSV. Splenocytes stimulated by anti-CD3 Ab were inhibited by SSV-induced Abs using CFSE labeling. SSV immunization in rats before heterotopic heart transplantation resulted in significant prolonged allograft survival. These findings suggested that SSV is a functional histone H1-binding epitope for 16G9 mAb. SSV is capable of determining serum immunoreactivity against histone H1 as an index marker for tolerance. The inhibitory activity of SSV-induced Abs on blast cell proliferation and the prolonged graft survival that results from SSV immunization imply a potential for the development of an immunosuppressive vaccine.
ICOS Controls Effector Function but Not Trafficking Receptor Expression of Kidney-Infiltrating Effector T Cells in Murine Lupus
Authors: Odegard Jared M. , DiPlacido Leah D. , Greenwald Lark , Kashgarian Michael , Kono Dwight H. , Dong Chen , Flavell Richard A. , Craft Joe
Published: March 2009

Renal pathology in systemic lupus erythematosus involves both autoantibody deposition and a cellular inflammatory response, both of which are mediated by effector CD4 T cells. MRLlpr mice spontaneously develop massive perivascular infiltrates, but the pathways that regulate the development, trafficking, and effector functions of kidney-infiltrating T cells are poorly defined. To address these questions, we first surveyed inflammatory chemokine protein levels in nephritic kidneys from lupus-prone MRLlpr mice. After identifying highly elevated levels of the CXCR3 ligand CXCL9, we found that kidney-infiltrating effectors are enriched for expression of CXCR3, as well as P-selectin ligand and ICOS. Using genetic ablation, we demonstrate that ICOS plays an essential role in the establishment of renal perivascular infiltrates, although a small number of infiltrating cells remain around the blood vessels. Interestingly, though IgG autoantibody production is substantially reduced in Icos−/− MRLlpr mice, the progression of immune complex glomerulonephritis is only modestly diminished and the production of inflammatory chemokines, such as CXCL9, remains high in the kidney. We find that Icos−/− effector cell numbers are only slightly reduced and these have normal expression of CXCR3 and P-selectin ligand with intact migration to CXCL9. However, they have impaired production of inflammatory cytokines and fail to show evidence of efficient proliferation in the kidney. Thus, while dispensable for acquisition of renal trafficking receptor expression, ICOS is strictly required for local inflammatory functions of autoreactive CD4 T cells in murine lupus.
Circulating Monocytes in HIV-1-Infected Viremic Subjects Exhibit an Antiapoptosis Gene Signature and Virus- and Host-Mediated Apoptosis Resistance
Authors: Giri Malavika S. , Nebozyhn Michael , Raymond Andrea , Gekonge Bethsebah , Hancock Aidan , Creer Shenoa , Nicols Calen , Yousef Malik , Foulkes Andrea S. , Mounzer Karam , Shull Jane , Silvestri Guido , Kostman Jay , Collman Ronald G. , Showe Louise , Montaner Luis J.
Published: March 2009

Mechanisms that may allow circulating monocytes to persist as CD4 T cells diminish in HIV-1 infection have not been investigated. We have characterized steady-state gene expression signatures in circulating monocytes from HIV-infected subjects and have identified a stable antiapoptosis gene signature comprised of 38 genes associated with p53, CD40L, TNF, and MAPK signaling networks. The significance of this gene signature is indicated by our demonstration of cadmium chloride- or Fas ligand-induced apoptosis resistance in circulating monocytes in contrast to increasing apoptosis in CD4 T cells from the same infected subjects. As potential mechanisms in vivo, we show that monocyte CCR5 binding by HIV-1 virus or agonist chemokines serves as independent viral and host modulators resulting in increased monocyte apoptosis resistance in vitro. We also show evidence for concordance between circulating monocyte apoptosis-related gene expression in HIV-1 infection in vivo and available datasets following viral infection or envelope exposure in monocyte-derived macrophages in vitro. The identification of in vivo gene expression associated with monocyte resistance to apoptosis is of relevance to AIDS pathogenesis since it would contribute to: 1) maintaining viability of infection targets and long-term reservoirs of HIV-1 infection in the monocyte/macrophage populations, and 2) protecting a cell subset critical to host survival despite sustained high viral replication.
Histoplasma capsulatum Cell Wall β-Glucan Induces Lipid Body Formation through CD18, TLR2, and Dectin-1 Receptors: Correlation with Leukotriene B4 Generation and Role in HIV-1 Infection
Authors: Sorgi Carlos Artério , Secatto Adriana , Fontanari Caroline , Turato Walter Miguel , Belangér Caroline , de Medeiros Alexandra Ivo , Kashima Simone , Marleau Sylvie , Covas Dimas Tadeu , Bozza Patrícia Torres , Faccioli Lúcia Helena
Published: March 2009

Histoplasma capsulatum (Hc) is a facultative, intracellular parasite of worldwide significance. Infection with Hc produces a broad spectrum of diseases and may progress to a life-threatening systemic disease, particularly in individuals with HIV infection. Resolution of histoplasmosis is associated with the activation of cell-mediated immunity, and leukotriene B4 plays an important role in this event. Lipid bodies (LBs) are increasingly being recognized as multifunctional organelles with roles in inflammation and infection. In this study, we investigated LB formation in histoplasmosis and its putative function in innate immunity. LB formation in leukocytes harvested from Hc-infected C57BL/6 mice peaks on day 2 postinfection and correlates with enhanced generation of lipid mediators, including leukotriene B4 and PGE2. Pretreatment of leukocytes with platelet-activating factor and BLT1 receptor antagonists showed that both lipid mediators are involved in cell signaling for LB formation. Alveolar leukocytes cultured with live or dead Hc also presented an increase in LB numbers. The yeast alkali-insoluble fraction 1, which contains mainly β-glucan isolated from the Hc cell wall, induced a dose- and time-dependent increase in LB numbers, indicating that β-glucan plays a signaling role in LB formation. In agreement with this hypothesis, β-glucan-elicited LB formation was inhibited in leukocytes from 5-LO−/−, CD18low and TLR2−/− mice, as well as in leukocytes pretreated with anti-Dectin-1 Ab. Interestingly, human monocytes from HIV-1-infected patients failed to produce LBs after β-glucan stimulation. These results demonstrate that Hc induces LB formation, an event correlated with eicosanoid production, and suggest a role for these lipid-enriched organelles in host defense during fungal infection.
Airway and Lung Pathology Due to Mucosal Surface Dehydration in β-Epithelial Na+ Channel-Overexpressing Mice: Role of TNF-α and IL-4Rα Signaling, Influence of Neonatal Development, and Limited Efficacy of Glucocorticoid Treatment
Authors: Livraghi Alessandra , Grubb Barbara R. , Hudson Elizabeth J. , Wilkinson Kristen J. , Sheehan John K. , Mall Marcus A. , O'Neal Wanda K. , Boucher Richard C. , Randell Scott H.
Published: March 2009

Overexpression of the epithelial Na+ channel β subunit (Scnn1b gene, βENaC protein) in transgenic (Tg) mouse airways dehydrates mucosal surfaces, producing mucus obstruction, inflammation, and neonatal mortality. Airway inflammation includes macrophage activation, neutrophil and eosinophil recruitment, and elevated KC, TNF-α, and chitinase levels. These changes recapitulate aspects of complex human obstructive airway diseases, but their molecular mechanisms are poorly understood. We used genetic and pharmacologic approaches to identify pathways relevant to the development of Scnn1b-Tg mouse lung pathology. Genetic deletion of TNF-α or its receptor, TNFR1, had no measurable effect on the phenotype. Deletion of IL-4Rα abolished transient mucous secretory cell (MuSC) abundance and eosinophilia normally observed in neonatal wild-type mice. Similarly, IL-4Rα deficiency decreased MuSC and eosinophils in neonatal Scnn1b-Tg mice, which correlated with improved neonatal survival. However, chronic lung pathology in adult Scnn1b-Tg mice was not affected by IL-4Rα status. Prednisolone treatment ablated eosinophilia and MuSC in adult Scnn1b-Tg mice, but did not decrease mucus plugging or neutrophilia. These studies demonstrate that: 1) normal neonatal mouse airway development entails an IL-4Rα-dependent, transient abundance of MuSC and eosinophils; 2) absence of IL-4Rα improved neonatal survival of Scnn1b-Tg mice, likely reflecting decreased formation of asphyxiating mucus plugs; and 3) in Scnn1b-Tg mice, neutrophilia, mucus obstruction, and airspace enlargement are IL-4Rα- and TNF-α-independent, and only MuSC and eosinophilia are sensitive to glucocorticoids. Thus, manipulation of multiple pathways will likely be required to treat the complex pathogenesis caused by airway surface dehydration.
Cutting Edge: Ikaros Null Thymocytes Mature into the CD4 Lineage with Reduced TCR Signal: A Study Using CD3ζ Immunoreceptor Tyrosine-Based Activation Motif Transgenic Mice
Authors: Urban Julie A. , Brugmann William , Winandy Susan
Published: March 2009

Positive selection is a critical T cell developmental checkpoint that is driven by TCR signals. Enhanced positive selection toward the CD4 lineage occurs in the absence of Ikaros. One explanation for this phenotype is that Ikaros establishes the TCR signaling threshold that must be overcome for positive selection to occur. In the current study, this possibility is explored through the use of CD3ζ ITAM transgenic mice that express a CD3 ζ-chain with zero, one, or three ITAMs and an MHC class II (DO11.10)- or MHC class I (H-Y)-restricted TCR transgene. Using this system, we demonstrate that in the absence of Ikaros, thymocytes are able to mature into the CD4 lineage with reduced TCR signaling potential compared with that required to drive the maturation of wild-type thymocytes. We also demonstrate that maturation into the CD8 lineage is enhanced under conditions of reduced TCR signaling potential in the absence of Ikaros.
The Cyclic AMP Response Element Modulator α Suppresses CD86 Expression and APC Function
Authors: Ahlmann Martina , Varga Georg , Sturm Karsten , Lippe Ralph , Benedyk Konrad , Viemann Dorothee , Scholzen Thomas , Ehrchen Jan , Müller Frank U. , Seidl Matthias , Matus Marek , Tsokos George C. , Roth Johannes , Tenbrock Klaus
Published: March 2009

The cAMP response element modulator (CREM)α is a widely expressed transcriptional repressor that is important for the termination of the T cell immune response and contributes to the abnormal T cell function in patients with systemic lupus erythematosus. We present evidence that APCs of Crem−/− mice express increased amounts of the costimulatory molecule CD86 and induce enhanced Ag-dependent and Ag-independent T cell proliferation. Similarly, human APCs in which CREMα was selectively suppressed expressed more CD86 on the surface membrane. CREMα was found to bind to the CD86 promoter and suppressed its activity. Transfer of APCs from Crem−/− mice into naive mice facilitated a significantly stronger contact dermatitis response compared with mice into which APCs from Crem+/+ mice had been transferred. We conclude that CREMα is an important negative regulator of costimulation and APC-dependent T cell function both in vitro and in vivo.
Cross-Linking of GM1 Ganglioside by Galectin-1 Mediates Regulatory T Cell Activity Involving TRPC5 Channel Activation: Possible Role in Suppressing Experimental Autoimmune Encephalomyelitis
Authors: Wang Jianfeng , Lu Zi-Hua , Gabius Hans-Joachim , Rohowsky-Kochan Christine , Ledeen Robert W. , Wu Gusheng
Published: March 2009

Several animal autoimmune disorders are suppressed by treatment with the GM1 cross-linking units of certain toxins such as B subunit of cholera toxin (CtxB). Due to the recent observation of GM1 being a binding partner for the endogenous lectin galectin-1 (Gal-1), which is known to ameliorate symptoms in certain animal models of autoimmune disorders, we tested the hypothesis that an operative Gal-1/GM1 interplay induces immunosuppression in a manner evidenced by both in vivo and in vitro systems. Our study of murine experimental autoimmune encephalomyelitis (EAE) indicated suppressive effects by both CtxB and Gal-1 and further highlighted the role of GM1 in demonstrating enhanced susceptibility to EAE in mice lacking this ganglioside. At the in vitro level, polyclonal activation of murine regulatory T (Treg) cells caused up-regulation of Gal-1 that was both cell bound and released to the medium. Similar activation of murine CD4+ and CD8+ effector T (Teff) cells resulted in significant elevation of GM1 and GD1a, the neuraminidase-reactive precursor to GM1. Activation of Teff cells also up-regulated TRPC5 channels which mediated Ca2+ influx upon GM1 cross-linking by Gal-1 or CtxB. This involved co-cross-linking of heterodimeric integrin due to close association of these α4β1 and α5β1 glycoproteins with GM1. Short hairpin RNA (shRNA) knockdown of TRPC5 in Teff cells blocked contact-dependent proliferation inhibition by Treg cells as well as Gal-1/CtxB-triggered Ca2+ influx. Our results thus indicate GM1 in Teff cells to be the primary target of Gal-1 expressed by Treg cells, the resulting co-cross-linking and TRPC5 channel activation contributing importantly to the mechanism of autoimmune suppression.
Inhibition of cAMP Degradation Improves Regulatory T Cell-Mediated Suppression
Authors: Bopp Tobias , Dehzad Nina , Reuter Sebastian , Klein Matthias , Ullrich Nina , Stassen Michael , Schild Hansjörg , Buhl Roland , Schmitt Edgar , Taube Christian
Published: March 2009

Naturally occurring regulatory T cells (nTreg cells) are crucial for the maintenance of peripheral tolerance. We have previously shown that a key mechanism of their suppressive action is based on a contact-dependent transfer of cAMP from nTreg cells to responder T cells. Herein, we further elucidate the important role of cAMP for the suppressive properties of nTreg cells. Prevention of cAMP degradation by application of the phosphodiesterase 4 inhibitor rolipram led to strongly increased suppressive potency of nTreg cells for Th2 cells in vitro and in vivo. Detailed analyses revealed that rolipram caused, in the presence of nTreg cells, a synergistic increase of cAMP in responder Th2 cells. In vivo, the application of nTreg cells in a strictly Th2-dependent preclinical model of asthma had only a marginal effect. However, the additional treatment with rolipram led to a considerable reduction of airway hyperresponsiveness and inflammation in a prophylactic as well as in a therapeutic model. This amelioration was correlated with enhanced cAMP-levels in lung Th2 cells in vivo. Collectively, these data support our observation that cAMP has a key function for nTreg cell-based suppression and they clearly demonstrate that the effect of cAMP on T responder cells can be greatly enhanced upon application of phosphodiesterase 4 inhibitors.
Cutting Edge: Dok-1 and Dok-2 Adaptor Molecules Are Regulated by Phosphatidylinositol 5-Phosphate Production in T Cells
Authors: Guittard Geoffrey , Gérard Audrey , Dupuis-Coronas Sophie , Tronchère Hélène , Mortier Eva , Favre Cédric , Olive Daniel , Zimmermann Pascale , Payrastre Bernard , Nunès Jacques A.
Published: March 2009

Downstream of tyrosine kinase (Dok) proteins Dok-1 and Dok-2 are involved in T cell homeostasis maintenance. Dok protein tyrosine phosphorylation plays a key role in establishing negative feedback loops of T cell signaling. These structurally related adapter molecules contain a pleckstrin homology (PH) domain generally acting as a lipid/protein-interacting module. We show that the presence of this PH domain is necessary for the tyrosine phosphorylation of Dok proteins and their negative functions in T cells. We find that Dok-1/Dok-2 PH domains bind in vitro to the rare phosphoinositide species, phosphatidylinositol 5-phosphate (PtdIns5P). Dok tyrosine phosphorylation correlates with PtdIns5P production in T cells upon TCR triggering. Furthermore, we demonstrate that PtdIns5P increase regulates Dok tyrosine phosphorylation in vivo. Together, our data identify a novel lipid mediator in T cell signaling and suggest that PH-PtdIns5P interactions regulate T cell responses.
Inorganic Drug‐Delivery Nanovehicle Conjugated with Cancer‐Cell‐Specific Ligand
Authors: Oh Jae‐Min , Choi Soo‐Jin , Lee Go‐Eun , Han Sun‐Ho , Choy Jin‐Ho
Published: March 2009

The surface of layered double hydroxide nanoparticles, a potential drug‐delivery nanovehicle, is modified with the cancer‐cell‐specific ligand, folic acid. The surface modification is successfully accomplished through step‐by‐step coupling reactions with aminopropyltriethoxysilane and 1‐ethyl‐3‐(3‐dimethyl aminopropyl)‐carbodiimide. In order to evaluate the cancer‐cell targeting effect of folic‐acid‐grafted layered double hydroxide utilizing fluorescence‐related assay, both layered double hydroxide with and without folic acid moiety are labeled with fluorescein 5′‐isothiocyanate. The uptake of layered double hydroxide and folic acid conjugated into KB and A549 cells is visualized using fluorescence microscopy and measured by flow cytometry. Both chemical and biological assay results demonstrate that the folic acid molecules are indeed conjugated to the surface of layered double hydroxide and thus the selectivity of nanovehicles to cancer cells overexpressing folate receptors increases. In this study, it is suggested that layered double hydroxide nanoparticles can be used as drug‐delivery carriers with a targeting function due to the chemical conjugation with specific ligand.
Stabilization of PbS Nanocrystals by Bovine Serum Albumin in its Native and Denatured States
Authors: Bakshi Mandeep Singh , Thakur Pankaj , Kaur Gurinder , Kaur Harpreet , Banipal Tarlok Singh , Possmayer Fred , Petersen Nils O.
Published: March 2009

PbS nanocrystals (NCs) are synthesized in aqueous phase within a temperature range of 40–80 °C in the presence of native and denatured states of bovine serum albumen (BSA) as the capping/stabilizing agent. The NCs are characterized with the help of field‐emission scanning electron microscopy, high‐resolution transmission electron microscopy, X‐ray diffraction, and energy‐dispersive X‐ray analysis. At 40 °C, large ball‐shaped NCs (145 ± 37 nm) with small surface protrusions are formed when 1 × 10−4 g mL−1 BSA is used. As the reaction temperature is increased towards 80 °C, the size of NCs decreases and they acquire somewhat cubic geometries (49.1 ± 7.0 nm) due to a change in the capping behavior of BSA between its native and denatured states. The native and denatured states of BSA are simultaneously studied by fluorescence spectroscopy using tryptophan emission, and pH measurements with respect to time and temperature. Gel electrophoresis is used to determine the polarity of the BSA capped NCs. Only the small sized NCs conjugated with relatively larger amounts of BSA show a displacement towards the positively charged electrode in comparison to larger NCs with lower amounts of BSA capping. It was concluded that the denatured state of BSA is more effective in controlling the crystal growth of PbS than its native state especially in the low concentration range.
Photocatalytic Carbon‐Nanotube–TiO2 Composites
Authors: Woan Karran , Pyrgiotakis Georgios , Sigmund Wolfgang
Published: March 2009

The literature and advances in photocatalysis based on the combination of titania (TiO2) and carbon nanotubes is presented. The semiconductor basis for photocatalysis is introduced for anatase and rutile. Furthermore, the proposed mechanisms of catalytic enhancement resulting from the pairing of the titania semiconductor with either metallic, semiconducting, or defect‐rich carbon nanotubes (CNT) is discussed. Differences are apparent for the mixtures and chemically bonded CNT–TiO2 composites. The article then highlights the recent advances in the synthesis techniques for these composites and their photocatalytic reactions with organic, inorganic, and biological agents. Finally, various applications and challenges for these composite materials are reported.
A comparison of physiological variables in aged and young women during and following submaximal exercise
Authors: Deschenes Michael R. , Connell Alastair M. , Jackson Erica M. , Taylor Jessica L. , Glass Emily K.
Published: March 2009

Previously, we have examined how aging affects the physiological responses of men to endurance exercise. In the present investigation, we aimed to extend our assessment of the influence of aging on exercise‐induced responses by focusing on women. Ten young (20.3 ± 0.3 years; mean ± SE) and 10 aged (75.5 ± 1.2 years) women performed 30 min of cycling at 60–65% of their predetermined peak oxygen uptake. Data for respiratory exchange ratio (RER), heart rate, blood pressure, rectal temperature, and plasma metabolites were collected before exercise, at the 15th and 30th min of exercise, and at 5 and 15 min postexercise. A two‐way, repeated measures ANOVA with main effects of age and time was conducted on each variable. Our findings showed that age affected exercise‐induced responses of each variable quantified. Although RER, heart rate, temperature, and lactate were significantly (P< 0.05) higher among young women, blood pressure and glucose values were greater among aged women. Moreover, unlike previous results noted among men where age‐related differences primarily occurred during postexercise recovery, in women the effect of aging was detected during exercise itself. The data presented here indicate that aging impacts physiological responses of women to prolonged endurance exercise even when relative intensity (% of peak oxygen uptake) is held constant. Combined with our earlier study on men, these findings suggest that gender interacts with aging to determine whether age‐related differences are manifested during exercise itself, or during postexercise recovery. Am. J. Hum. Biol., 2009. © 2009 Wiley‐Liss, Inc.