bluuebunny/crossref_metadata_2025 huggingface dataset:
Proinflammatory T helper type 17 cells are effective B-cell helpers
Authors: Mitsdoerffer Meike , Lee Youjin , Jäger Anneli , Kim Hye-Jung , Korn Thomas , Kolls Jay K. , Cantor Harvey , Bettelli Estelle , Kuchroo Vijay K.
Published: July 2010

T helper type 17 (TH17) cells are highly proinflammatory effector T cells that are characterized by the production of high amounts of IL-17A, IL-17F, IL-21, and IL-22. Furthermore, TH17 cells have been associated with a number of autoimmune diseases. However, it is not clear whether TH17 cells can also serve as effective helper cells. Here we show that TH17 cells can function as B-cell helpers in that they not only induce a strong proliferative response of B cells in vitro but also trigger antibody production with class switch recombination in vivo. Transfer of TH17 cells into WT or T-cell receptor α–deficient mice, which lack endogenous T cells, induces a pronounced antibody response with preferential isotype class switching to IgG1, IgG2a, IgG2b, and IgG3, as well as the formation of germinal centers. Conversely, blockade of IL-17 signaling results in a significant reduction in both number and size of germinal centers. Whereas IL-21 is known to help B cells, IL-17 on its own drives B cells to undergo preferential isotype class switching to IgG2a and IgG3 subtypes. These observations provide insights into the unappreciated role of TH17 cells and their signature cytokines in mediating B-cell differentiation and class switch recombination.
Protein damage and death by radiation in
Escherichia coli
and
Deinococcus radiodurans
Authors: Krisko Anita , Radman Miroslav
Published: July 2010

Deinococcus radiodurans
is among a small number of bacterial species that are extremely resistant to ionizing radiation, UV light, toxic chemicals, and desiccation. We measured proteome oxidation (i.e., protein carbonylation, PC) in
D. radiodurans
as well as in standard and evolved resistant strains of
Escherichia coli
exposed to ionizing radiation or UVC light and found a consistent correlation with cell killing. The unique quantitative relationship between incurred PC and cell death holds over the entire range of killing for all tested bacteria and for both lethal agents, meaning that both bacterial species are equally sensitive to PC. We show that the extraordinary robustness of
D. radiodurans
depends on efficient proteome protection (but not DNA protection) against constitutive and radiation-induced PC consisting of low molecular weight cytosolic compounds. Remarkably, experimental evolution of resistance to ionizing radiation in
E. coli
coevolves with protection against PC. The decline in biosynthetic efficacy of the cellular proteome, as measured by the loss of reproduction of undamaged bacteriophage λ in irradiated standard and evolved ionizing radiation-resistant
E. coli
, correlates with radiation-induced oxidative damage to host cells and their sensitivity to ionizing radiation. This correlation suggests that cell death by radiation is caused primarily by oxidative damage with consequential loss of maintenance activities including DNA repair.
Promotion of direct reprogramming by transformation-deficient Myc
Authors: Nakagawa Masato , Takizawa Nanako , Narita Megumi , Ichisaka Tomoko , Yamanaka Shinya
Published: July 2010

Induced pluripotent stem cells (iPSCs) are generated from mouse and human fibroblasts by the introduction of three transcription factors: Oct3/4, Sox2, and Klf4. The proto-oncogene product c-Myc markedly promotes iPSC generation, but also increases tumor formation in iPSC-derived chimeric mice. We report that the promotion of iPSC generation by Myc is independent of its transformation property. We found that another Myc family member, L-Myc, as well as c-Myc mutants (W136E and dN2), all of which have little transformation activity, promoted human iPSC generation more efficiently and specifically compared with WT c-Myc. In mice, L-Myc promoted germline transmission, but not tumor formation, in the iPSC-derived chimeric mice. These data demonstrate that different functional moieties of the Myc proto-oncogene products are involved in the transformation and promotion of directed reprogramming.
Genome-wide analysis reveals mechanisms modulating autophagy in normal brain aging and in Alzheimer's disease
Authors: Lipinski Marta M. , Zheng Bin , Lu Tao , Yan Zhenyu , Py Bénédicte F. , Ng Aylwin , Xavier Ramnik J. , Li Cheng , Yankner Bruce A. , Scherzer Clemens R. , Yuan Junying
Published: July 2010

Dysregulation of autophagy, a cellular catabolic mechanism essential for degradation of misfolded proteins, has been implicated in multiple neurodegenerative diseases. However, the mechanisms that lead to the autophagy dysfunction are still not clear. Based on the results of a genome-wide screen, we show that reactive oxygen species (ROS) serve as common mediators upstream of the activation of the type III PI3 kinase, which is critical for the initiation of autophagy. Furthermore, ROS play an essential function in the induction of the type III PI3 kinase and autophagy in response to amyloid β peptide, the main pathogenic mediator of Alzheimer's disease (AD). However, lysosomal blockage also caused by Aβ is independent of ROS. In addition, we demonstrate that autophagy is transcriptionally down-regulated during normal aging in the human brain. Strikingly, in contrast to normal aging, we observe transcriptional up-regulation of autophagy in the brains of AD patients, suggesting that there might be a compensatory regulation of autophagy. Interestingly, we show that an AD drug and an AD drug candidate have inhibitory effects on autophagy, raising the possibility that decreasing input into the lysosomal system may help to reduce cellular stress in AD. Finally, we provide a list of candidate drug targets that can be used to safely modulate levels of autophagy without causing cell death.
Tumor masses support naive T cell infiltration, activation, and differentiation into effectors
Authors: Thompson Elizabeth D. , Enriquez Hilda L. , Fu Yang-Xin , Engelhard Victor H.
Published: July 2010

Studies of T cell responses to tumors have focused on the draining lymph node (LN) as the site of activation. We examined the tumor mass as a potential site of activation after adoptive transfer of naive tumor-specific CD8 T cells. Activated CD8 T cells were present in tumors within 24 h of adoptive transfer and proliferation of these cells was also evident 4–5 d later in mice treated with FTY720 to prevent infiltration of cells activated in LNs. To confirm that activation of these T cells occurred in the tumor and not the tumor-draining LNs, we used mice lacking LNs. Activated and proliferating tumor-infiltrating lymphocytes were evident in these mice 24 h and 4 d after naive cell transfer. T cells activated within tumors acquired effector function that was evident both ex vivo and in vivo. Both cross-presenting antigen presenting cells within the tumor and tumor cells directly presenting antigen activated these functional CD8 effectors. We conclude that tumors support the infiltration, activation, and effector differentiation of naive CD8 T cells, despite the presence of immunosuppressive mechanisms. Thus, targeting of T cell activation to tumors may present a tool in the development of cancer immunotherapy.
Theoretical Studies of O(1D) + HD (v= 0,j= 0, 1, 2, 3) → OD(H) + H(D) Reaction
Authors: Li Ya-min , Xie Zhi-min , Dang Qiong
Published: July 2010

The quasi-classical trajectory calculation for the reaction O(1D) + HD is carried out based on the Dobbyn and Knowles potential energy surface. In this work, the reaction cross section and product branching ratio are obtained. The product branching ratio OD/OH was discussed. The calculated results show that the cross-section decreases thoroughly with the increasing of the collision energy from 4.6 kJ/mol to 46.0 kJ/mol. The average branching ratio decrease with the increase of rotational quantum number of reactant HD.
Shear Thickening Fluids Based on Additives with Different Concentrations and Molecular Chain Lengths
Authors: Xu Yu-lei , Gong Xing-long , Peng Chao , Sun Ying-qiang , Jiang Wan-quan , Zhang Zhong
Published: July 2010

Shear thickening fluids (STFs) based on additives with different concentrations and molecular chain lengths were investigated. STF samples were prepared with silica and additive dispersed in polyethylene glycol (PEG) 400, where three types of additives with different molecular chain lengths of PEG4000, PEG6000, and PEG10000 were used. For PEG10000, different concentrations, including 0, 1%, 3%, and 5%, were selected to study the influences of additive concentrations. Rheological properties of the samples were measured with a rheometer. The results show that the shear thickening effect was significantly enhanced with the increase of the concentration and the molecular chain length of additives. The mechanism of enhancement was quantitatively explained with the formation of large particles clusters.
Oriented Growth of Tin Oxide Thin Films on Glass Substrates by Spray Pyrolysis of Organotin Compounds
Authors: Murakami Kenji , Yagi Isao , Kaneko Shoji
Published: July 2010

Organotin compounds were used successfully to prepare highly oriented SnO2 thin films on glass substrates. Spray pyrolysis of tetra‐n‐butyltin(IV) and di‐n‐butyltin(IV) diacetate led to the deposition of [110]‐ and [200]‐oriented SnO2 films, respectively. The oriented growth of these thin films occurred via three stages: (1) formation of SnO2 nuclei, (2) crystal growth of SnO2 with preferred orientations, and (3) further crystal growth normal to the surface of the substrate. The butyl and acetoxy groups of the organotin compounds facilitated [110]‐ and [200]‐oriented growth of SnO2 thin films, respectively. The present model explains the oriented growth of SnO2 thin films in terms of the relationship between the molecular structure of the starting compounds and the atomic configuration of the grown surfaces.
Structure and Mechanical Properties of Copper/Niobium Multilayers
Authors: Mitchell Terence E. , Lu Yong Cheng , Jr. Alfred J. Griffin , Nastasi Michael , Kung Harriet
Published: July 2010

Copper/niobium multilayers prepared by sputtering onto Si substrates with layer thicknesses ranging from 11 to 5000 Å have been characterized by transmission electron microscopy and nanoindentation. The films are strongly textured with {110} close‐packed planes of the bcc Nb parallel to the {111} close‐packed planes of the fcc Cu and close‐packed directions tending to be parallel as well. For the 11 Å layers, the Cu is found to grow pseudomorphically on Nb in the bcc structure. It is thought that, for thicker layers, the bcc Cu loses coherency and transforms martensitically to the fcc phase, thus resulting in the observed Kurdjumov—Sachs orientation relationship. As the layer thickness, d, decreases from 5000 to 500 Å, the hardness increases as d‐1/2; i.e., it follows a Hall—Petch relationship so that hardening is due to grain boundaries and interfaces. The slope is the same as in pure Cu, but there is a large intercept which is ascribed to internal stresses and a large dislocation density. As the layer thickness decreases from 100 to 11 Å, the hardness increases as (1/d) ln (0.69d), which is a line tension formulation such as would be expected for Orowan dislocation bowing between the layers. Again there is a large intercept which is ascribed to cutting through the Cu/Nb interfaces. The interfacial energy is calculated to be 0.46 J/m2.
Hot Isostatically Pressed SiC‐AIN Powder Mixtures: Effect of Milling on Solid‐Solution Formation and Related Properties
Authors: Li Jing‐Feng , Kawasaki Akira , Watanabe Ryuzo
Published: July 2010

Powder mixtures with nominal compositions of 75 mol% SiC and 25 mol% AlN as well as 50 mol% SiC and 50 mol% AlN were prepared by ball milling for 1‐300 h and subsequently sintered to full density by hot isostatic pressing (HIPing) at 1850°C under a pressure of 200 MPa. Microstructures and properties of the HIP‐sintered SiC‐AlN powder mixtures were investigated with special attention to the effect of ball milling on the formation of SiC‐AlN solid solutions. Extensive ball milling facilitated effectively the formation of solid solutions by improvement in mixing homogeneity and pulverization of the SiC and AlN powders. Thermal conductivity of the HIP‐sintered SiC‐AlN powder mixtures decreased remarkably with ball‐milling time, mainly because of the enhanced formation of solid solutions. Mechanical properties‐such as strength, fracture toughness, and microhardness‐were dependent on the microstructural homogeneity and the grain refinement resulting from the formation of solid solutions.
Strain Rate Dependence of the Hardness of Glass and Meyer's Law
Authors: Grau Peter , Berg Gunnar , Meinhard Holger , Mosch Susan
Published: July 2010

Depth‐sensing Vickers hardness test on glass for various loading regimes were analyzed by applying a flow law for material deformation behavior used by Han and Tomozawa, who investigated the creep behavior of glassy materials during indentation experiments. Load, indentation depth, and time were measured simultaneously at deformation rates covering 6 orders of magnitude. In all cases, the results yielded the well‐known Meyer hardness law, by which the parameters of flow law are unequivocally determined using experimentally estimated Meyer parameters. Experiments conducted with various dependencies on commercial sheet glass all gave material parameters in good agreement. Differences originating from different loading regimes must be resolved in future works.
Shock Synthesis of a Graphitic Boron‐Carbon‐Nitrogen System
Authors: Yamada Kenjiro
Published: July 2010

Fine graphitelike boron‐carbon‐nitrogen particles were produced via vaporization and condensation of a powdered mixture of amorphous boron nitride/carbon black (a‐BN/CB) via shock compression. Electron microscopy showed that the particles were made of a graphitic layer sequence with a composition of (BN)0.33C0.67. The hexagonal lattice parameters of g‐(BN)0.33C0.67 were a0= 0.2475 ± 0.0001 nm and c0= 0.676 ± 0.002 nm.
High‐Pressure Phase Behavior of Alumina: Predictions of a Transferable Ionic Potential Model
Authors: Wilson Mark
Published: July 2010

A recently introduced potential model for alumina has been used to study a wider range of structures than previously attempted. The model contains both the spherical relaxation of, and induced dipoles and quadrupoles on, the oxide anions. The model is applied to the possible high‐pressure phase transition from the ground‐state corundum structure to the Rh2O3‐II structure. A transition pressure of 194 GPa has been predicted, which is in excellent agreement with the most‐recent experimental results. The spherical relaxation and induced quadrupoles are crucial in effectively modeling the transition. The shortcomings of the model are assessed by comparison with experiment and both ab initioand model calculations. Other structures common in this stoichiometry have also been considered.
Morphology of Silicon Nitride Grown from a Liquid Phase
Authors: Wang Ling‐Ling , Tien Tseng‐Ying , Chen I‐Wei
Published: July 2010

To explain the recent experimental observation of liquid‐grown silicon nitride (Si3N4) crystals with a concave depression in the center of the (0001) end face, we propose a new growth mechanism and develop an analytical solution for the steady state. The model allows for atoms that diffuse via the liquid to the side surface but demands that the majority of these atoms be transported to the end caps to feed axial growth. The analysis shows that, for a large radius crystal, the redistribution of atoms by surface diffusion on the end caps requires a long relaxation time; hence, a nonequilibrium shape results. For an isolated Si3N4 crystal growing in a liquid environment, the shape of the end cap is largely determined by the ratio of the supersaturation to the equilibrium surface potential, which is inversely proportional to the crystal radius. A large shape distortion is predicted to occur during the growth stage for large‐radius crystals and during the coarsening stage for a population of crystals with a large size distribution. This mechanism ceases to operate when the liquid flux to the side surface is blocked, as in silicon nitride ceramics, but is otherwise insensitive to factors such as radial growth kinetics and liquid diffusivity.
Weibull Parameters and the Tensile Strength of Porous Phosphate Glass‐Ceramics
Authors: Pernot François , Etienne Pascal , Boschet Frédéric , Datas Lucien
Published: July 2010

The strengths of porous phosphate glass‐ceramic specimens, with relative densities ranging between 0.25 and 0.50, were measured by four‐point bending at room temperature. An analysis of the data, using Weibull statistics, indicated that such a treatment, usually performed on dense ceramics, can also be used on porous materials. In the sets studied, the nature of critical flaws was determined, which led to the proposal of a mechanism of fracture initiation in such porous materials.
Direct Coagulation Casting of Silicon Carbide Components
Authors: Si Wenjie , Graule Thomas J. , Baader Felix H. , Gauckler Ludwig J.
Published: July 2010

Direct coagulation casting is a novel near‐net‐shape method for forming ceramic green bodies from homogenous high‐solids‐loaded particle suspensions. It is based on the principle of the in situcoagulation of a powder suspension via a reaction‐rate‐controlled internal‐enzyme(urease)‐catalyzed reaction after casting. Low‐viscosity (<3 Pas) suspensions with a high solids loading (>62 vol%) of SiC, boron, and carbon powder mixtures with a high surface area (>7‐10 m2/g) have been prepared at pH = 10. Salt ions (up to 1‐2 mol/L) are created by the urease‐catalyzed decomposition of urea, to destabilize the suspensions. The coagulation kinetics and the strength of the wet green bodies have been investigated. The reaction rate is strongly dependent on the temperature (in the range of 5°‐30°C) and the enzyme concentration (for the range of 4‐16 units/g SiC) and is independent of the substrate (urea) concentration for urea concentrations of <2 wt%, based on the powder content. The resulting green bodies show no shrinkage during coagulation and 1%‐2% linear shrinkage during drying. The compressive strengths of the wet green bodies are as high as 60 kPa and increase as the coagulation time increases. The wet green strength of the coagulated suspensions scales with the solids content, according to a power law with an exponent of 11, in the range of 56‐61 vol% solids content. The possibilities of fabricating high‐solids‐containing complex SiC green and sintered components with homogenous microstructures and high sintered densities are demonstrated.
Indentation Determination of Fatigue Limits in Silicate Glasses
Authors: Sglavo Vincenzo M. , Green David J.
Published: July 2010

An experimental approach has been used to measure the threshold stress intensity factor (Kth) for subcritical crack growth in brittle materials using indentation cracks. The data show that Kth values existed in soda‐lime‐silica and soda‐alumina‐silica glasses that were tested in a neutral aqueous environment. For the former glass, tests also were performed in acidic and basic solutions. A threshold for subcritical crack growth was observed for acidic conditions but not for alkaline conditions.
Thermal Oxidation Kinetics of MoSi2‐Based Powders
Authors: Zhu Yuntian T. , Stan Marius , Conzone Samuel D. , Butt Darryl P.
Published: July 2010

The oxidation process of MoSi2 is very complex, and controversial results have been reported, especially for the early‐stage oxidation before the formation of passive SiO2 film. Most oxidation studies have been carried out on bulk consolidated samples, and the early stage of oxidation has not been studied. In this investigation, very fine MoSi2 powder with an average particle size of 1.6 μm was used. Such a fine particle size makes it easier to study the early stages of oxidation since a significant portion of the powder is oxidized before the formation of passive SiO2 film. The oxidation kinetics of commercial MoSi2‐SiC and MoSi2‐Si3N4 powder mixtures were also studied for comparison. Weight changes were measured at discrete time intervals at 500° to 1100°C in 0.14 atm of oxygen. X‐ray diffraction was used to identify the phases formed during oxidation. Our results show the formation of MoO3 phase and an associated weight gain at low temperatures (500° and 600°C). At temperatures higher than 900°C, Mo5Si3 phase formed first and was subsequently oxidized to solid SiO2 and volatile MoO3, resulting in an initial weight gain followed by subsequent weight loss. A model based on the assumption that oxidation kinetics of both MoSi2 and Mo5Si3 are proportional to their fractions in the system describes the experimental data well.
Processing of Lightweight, High‐Strength Porcelains Using an Alumina Cement to Replace Feldspars and Clays
Authors: Tai Weon‐Pil , Kimura Kunio , Jinnai Kazuhiko
Published: July 2010

New lightweight, high‐strength porcelain bodies, using only nonplastic raw materials such as glass microspheres, quartz, and alumina cement, were fabricated and the effect of quartz particle size was investigated. Decreases in the green strength, relative to an increasing content of glass microspheres, were attributed to the decrease in the density and the relative decrease in the volume of alumina cement. The phases in the fired body were glass, α‐quartz, cristobalite, anorthite, and a small amount of α‐alumina. The large quartz particles (10–32 μm in size) could not be densified to closed porosity, because of underfiring, whereas smaller quartz particles (4–10 μm in size) permitted densification to closed porosity at 1300°C. The high flexural strength when using medium‐sized quartz particles (6–20 μm, content of 30 wt%) was attributed to a stronger prestress and higher density that was due to better vitrification.
Nonisothermal Synthesis of Yttria‐Stabilized Zirconia Nanopowder through Oxalate Processing: I, Characteristics of Y‐Zr Oxalate Synthesis and Its Decomposition
Authors: Vasylkiv Oleg , Sakka Yoshio
Published: July 2010

To obtain powder with a composition of 3 mol% Y2O3–97 mol% ZrO2, a process of Y‐Zr oxalate powder production has been optimized, to produce an oxalate with minimal particle size. The methodology of the nonisothermal decomposition of Y‐Zr oxalate has been explained. Characteristics of the nonisothermal decomposition of different oxalates have been studied. Nanocrystalline Y2O3‐stabilized ZrO2 (YSZ) powder with a narrow size distribution of primary particles and aggregates was produced. The zirconia powder that was obtained from the smallest oxalate powder via nonisothermal decomposition had a particle size of 8–10 nm. The YSZ powder was weakly aggregated, with a narrow aggregate‐size distribution of 70–90 nm.
Fabrication of Long Lengths of Epitaxial Buffer Layers on Biaxially Textured Nickel Substrates Using a Continuous Reel‐to‐Reel Dip‐Coating Unit
Authors: Paranthaman M. Parans , Chirayil Thomas G. , List Fred A. , Cui Xingtian , Goyal Amit , Lee Dominic F. , Specht Eliot D. , Martin Patrick M. , Williams Robert K. , Kroeger Donald M. , Morrell Jonathan S. , Beach David B. , Feenstra Ron , Christen David K.
Published: July 2010

A low‐cost, nonvacuum, solution precursor route has been developed to produce epitaxial oxide buffer layers of Eu2O3 or La2Zr2O7 on biaxially textured Ni (100) tapes. A reel‐to‐reel continuous dip‐coating unit consisting of a constant‐tension tape transport system attached to a controlled atmosphere furnace was fabricated. Nickel tapes were pulled through a 2‐methoxyethanol solution of europium methoxyethoxide/acetate or lanthanum zirconium methoxyethoxide. The double‐sided dip‐coated tapes were then annealed in a preheated furnace at 1000°–1100°C with a high flow rate of Ar/H2 (4%) gas. The dip‐coated buffers were dense, continuous, crack‐free, and epitaxial with a single cube texture. A critical current (Jc) of >1 MA/cm2 at 77 K and self‐field was obtained for YBa2Cu3O7‐δ (YBCO) films with a layer sequence of YBCO (ex situ BaF2 process)/CeO2 (sputtered)/YSZ (sputtered)/Eu2O3 (dip‐coated)/nickel. We have produced 1–2 m lengths of epitaxial buffer layers on textured nickel substrates using a nonvacuum process for the first time.
Study on the Effects of Lanthanum Doping on the Microstructure and Dielectric Properties of 0.9Pb(Mg1/3Nb2/3)O3–0.1PbTiO3
Authors: Winter Michael R. , Pilgrim Steven M. , Lejeune Martine
Published: July 2010

Lead magnesium niobate (Pb(Mg1/3Nb2/3)O3, or PMN) is a relaxor ferroelectric with many potential applications. As a relaxor ferroelectric, PMN displays a diffuse phase transition and its temperature of maximum relative permittivity (Tm) shifts to higher temperatures as the frequency increases. When 10 mol% of lead titanate (PbTiO3, or PT) is added, a solid solution is formed with aTmvalue near ambient temperature. These properties can be manipulated to serve many functions, such as applications in transducers, actuators, and active vibration‐control systems. The purpose of this experiment was to examine the effect of lanthanum doping on the microstructure and dielectric properties of a 0.9PMN–0.1PT solid solution. Lanthanum was added in concentrations of 0.0, 0.5, and 1.0 mol%. The samples were fired under different lead atmosphere conditions, to examine the effect of lead depletion. The presence of lanthanum had no effect on the grain structure of the fired samples; however, the grain size did increase when lead zirconate (PbZrO3) was added to the system to maintain a high partial pressure of lead. The addition of lanthanum also created a weak grain‐boundary phase, which led to intergranular fracture. Lanthanum doping decreased the maximum permittivity by ∼17% and decreased theTmvalue by 10°C for every 0.5 mol% of lanthanum that was added. The diffuseness of the permittivity‐versus‐temperature curve was described using both the fractional power parameter γ and the parameter δ, a la Smolenskii. Both parameters increased as lanthanum was added to the system, which indicated a broader transition. Lanthanum addition also decreased the high‐field polarization but did not have a conclusive effect on induced microstrain. Aging was not observed under any of the examined conditions.
Spark Plasma Sintering of Tungsten Bronze Sr2−xCaxNaNb5O15 (x= 0.1) Piezoelectric Ceramics: I, Processing and Microstructure
Authors: Xie Rong‐Jun , Akimune Yoshio , Wang Rui‐Ping , Matsuo Kazuo , Sugiyama Tatsuo , Hirosaki Naoto
Published: July 2010

Tungsten bronze Sr2−xCaxNaNb5O15 (SCNN, x= 0.1) piezoelectric ceramics were prepared by a novel super‐fast sintering technique, i.e., spark plasma sintering (SPS). Sintering was conducted at temperatures ranging from 1000° to 1200°C under vacuum under 35 MPa. The heating rate varied from 30° to 300°C/min and the soaking time was in the range of 5 to 60 min. The microstructure and the phase identification were analyzed via scanning electron microscopy (SEM) and X‐ray diffraction (XRD). The density of the sintered ceramics increased with an increase in sintering temperature as well as in heating rate. Materials with a near‐theoretical density could be attained by sintering at 1200°C for 5 min with a heating rate of 300°C/min, exhibiting a homogeneous and fine‐grained microstructure (grain size about 2.7 μm) and a uniform translucency. A tetragonal tungsten bronze phase was identified in ceramics sintered at temperatures above 1200°C, whereas the tungsten bronze phase transformed to a SrNb2O6‐type phase in the materials sintered at temperatures below 1200°C. XRD patterns demonstrated a preferred crystallographic orientation of the SCNN grains with their c‐axes perpendicular to the pressing direction.
The Fluidity Gradient in Erythrocyte Membranes in Hereditary Spherocytosis: a Spin Label Study
Authors: Jansson Sten‐Erik , Johnson Riia , Gripenberg Johan , Vuopio3 Pekka
Published: July 2010

Summary. The fluidity gradient and sulphydryl groups in erythrocyte ghost membranes from healthy subjects and from seven patients with hereditary spherocytosis (HS) Lvere studied by spin label techniques. The mobility of the stearic acid spin labels was lower in the spherocyte membranes, indicating greater stability of the phospholipid layer in these membranes than in those of matched controls. This stabilization was most distinct in the intermediate and deep membrane layers. No clear differences were observed in the protein sulphydryl groups. It is suggested that the decreased cellular deformability characterizing spherocytes reflects altered lipid organization or lipid‐protein interaction in the interior of the cell membrane.
Factor VII Deficiency: Immunological Characterization of Genetic Variants and Detection of Carriers
Authors: Mariani G. , Mazzucconi M. G. , Hermans J. , Ciavarella N. , Faiella A. , Hassan H. J. , Mannucci P. M. , Nenci G. G. , Orlando M. , Romoli D. , Mandelli F.
Published: July 2010

Summary. Twenty‐one patients with congenital factor VII deficiency belonging to 16 different kindreds were investigated. The existence of three immunochemical variants on the ground of factor VII activity (VII:C) and factor VII‐related antigen (VII:Ag) levels (VII−, VII+ and VIIR) was established. There was no correlation between the presence of factor VII:Ag and either the clinical picture or the specific function as studied with the Km calculations.

Genetically the mode of inheritance is the same whatever the immunological variant, but the identification of carriers is simplified when the presence of factor VII‐related antigen is assayed throughout a kindred.
The Platelet Count and Mean Platelet Volume
Authors: Giles C.
Published: July 2010

Summary. The Coulter Model S‐Plus Counter provides a measure of the platelet count and the mean platelet volume (MPV). An analysis of 5000 unselected blood specimens showed an inverse relationship between the number of circulating platelets and their MPV. In nearly 95% of normal adults the platelet count varied from 150 to 450 × 109/1 and the MPV from 7·0 to 10·5 fl. Thrombocytosis was found in iron deficiency anaemia, after trauma and acute blood loss and in rheumatoid arthritis. Although there is a normal platelet distribution in pregnancy, patients with pre‐eclampsia and uncomplicated hypertension in late pregnancy tended to have lower platelet counts and larger platelets than controls. A variable platelet pattern was found in infection, renal failure and treated malignant disease.
Aspiration of Bone Marrow from Laboratory Rats
Authors: Archer R. K. , Riley J. , Gwilliam R. V. E.
Published: July 2010

Summary. Bone marrow aspiration biopsies were made from the proximal end of the femur of rats using a newly developed needle.
Haemorrhagic Thrombocytopathy Associated with Dilatation of the Platelet—Membrane Complex
Authors: Green David , Ts'ao Chung‐hsin , Cohen Isaac , Rossi Ennio C.
Published: July 2010

Summary.

We evaluated eight patients from four families because of a history of excessive bleeding. Most patients had prolonged bleeding times, absent secondary wave of platelet aggregation in response to epinephrine, collagen and adenosine diphosphate (ADP), and defective 14C‐serotonin release and platelet factor 3 availability. These findings are characteristic of a platelet release defect. Electron‐microscopic examination of the platelets of seven patients revealed a common abnormality. From 30% to 70% of the platelets in any given sample exhibited a prominent membrane complex and dilated, tortuous surface‐connected canalicular system (‘swiss‐cheese’ platelet). In two patients there was coincident storage‐pool disease, but the remainder had adequate dense bodies and a normal ratio of ATP to ADP. SDS‐polyacrylamide gel electrophoresis of platelet proteins and glycoproteins showed no abnormalities. The patency of the canalicular system was demonstrated in one patient by the observation that dense bodies appeared in the cannaliculi and outside the platelets following collageninduced aggregation of polylysine‐treated platelets. Since platelet‐aggregation responses to the calcium ionophore A23187 were normal, we conclude that the defective platelet function in these patients may be due to impaired calcium mobilization from the morphologically abnormal membrane complex.
Coagulation Abnormalities following Intensive Plasma Exchange on the Cell Separator
Authors: Chirnside Ann , Urbaniak S. J. , Prowse C. V. , Keller A. J.
Published: July 2010

Summary.

The effects of intensive plasma exchange on the circulating levels of coagulation factors I, II, V, VII, VIII, IX, X and antithrombin III were determined. During courses of daily exchange marked cumulative reductions of coagulation factors may occur, particularly in the case of factors I, II and X, although usually remaining above the levels considered adequate for haemostasis. The extent of cumulative reduction and subsequent recovery differed for patients with different diseases. While antithrombin III levels were reduced during plasma exchange the results suggest that this may be partly due to consumption as well as physical removal.

The very low incidence of haemorrhagic sequelae and absence of thrombotic events following plasma exchange at this Centre is explained by the maintenance of adequate levels of coagulation factors and of antithrombin III even during courses of daily plasma exchange.
Dosage and control of oral anticoagulants: an international collaborative survey
Authors: Poller L. , Taberner D. A.
Published: July 2010

Summary.

An international survey of oral anticoagulant dosage has been carried out comparing the mean dosage prescribed in hospitals in 23 countries. In addition, participants using the Quick prothrombin time test were asked to assess the adequacy of dosage of a lyophilized test plasma which was mid‐therapeutic using the British Comparative Thromboplastin (BCT).

The overall mean dosage proved similar for the groups of laboratories using the Quick test and human brain thromboplastin and Thrombotest although wide differences existed between individual centres. The survey indicated that these discrepancies were due partly to the adoption of different intensities of anticoagulation. In addition, local differences in patients’response to anticoagulants were apparent, e.g. North American centres prescribed a higher mean dose with a more intense therapeutic range than Europeans. Hong Kong physicians appear to prescribe a much lower dose than the rest of the world although the intensity of their treatment is comparable, whereas South African hospitals give moderate doses of warfarin despite a conservative therapeutic range. Such geographical variation in response would invalidate standardization of anticoagulant treatment based on the mean dosage approach.
A new approach for the antenatal diagnosis of β‐thalassaemia: a double labelling immunofluorescence microscopy technique
Authors: Thorpe Susan J. , Huehns E. R.
Published: July 2010

Summary. A new approach to the antenatal diagnosis of β‐thalassaemia major (homozygous β‐thalassaemia) has been developed. Using rhodamine‐labelled antibodies directed against γ‐globin, fetal erythrocytes can be identified in fetal blood samples contaminated with maternal cells, and using fluorescein‐labelled antibodies directed against β‐globin, the presence of β‐chains (and thus Hb‐A) may be determined in the same cells by double labelling immunofluorescence microscopy. The results obtained using this technique on blood samples from fetuses at risk for β‐thalassaemia major show that if fetal β‐chains are detected immunochemically the fetus is normal or heterozygous for β‐thalassaemia and over 85% of the fetuses unaffected by β‐thalassaemia major may be identified in this way. The technique is rapid, applicable to small numbers of fetal erythrocytes heavily contaminated with maternal cells and eliminates the necessity of determining chain synthesis ratios in those cases where β‐chains are detected immunochemically.
Decreased T helper cells in the myelodysplastic syndromes
Authors: Bynoe A. G. , Scott C. S. , Ford P. , Roberts B. E.
Published: July 2010

Summary. The myelodysplastic syndromes (MDS) are disorders in which the abnormalities are thought to be confined to cells of the myeloid series. However, examination of peripheral blood from 56 patients with MDS showed that the majority had low lymphocyte counts. In a detailed study of 25 patients, using OKT3, OKT4 and OKT8 monoclonal antisera together with SRBC rosettes, it was shown that there is a consistent and significant reduction in peripheral blood T lymphocytes. This decrease was primarily confined to the OKT4‐defined helper subpopulation. There is a consequent relative increase in the OKT8‐defined subset but in absolute numbers however, suppressor cells are reduced compared to normal particularly in those patients with lymphopenia. No correlations between T cell abnormalities and the different morphological groups of MDS were found. The possible implications of the reversed helper/suppressor ratio in the pathogenesis of MDS are discussed.
Modifications of granulocyte subpopulations and of their adherence property during filtration leukapheresis in man
Authors: Silvani C.M. , Tedesco F. , And M. Marconi , Sirchia G.
Published: July 2010

Summary. Polymorphonuclear leucocytes (PMN) isolated from the peripheral blood of 23 blood donors undergoing filtration leukapheresis were examined with regard to their number, expression of membrane receptors for rabbit IgG or human C3b and their ability to adhere to nylon fibres. All the donors showed an early granulocytopenia followed by a gradual return of PMN into the circulation, but differed in the number of PMN appearing in the rebound phase. Evaluation of rosette forming cells (RFC) and cells adhering to nylon fibres in this phase led to the recognition of two main groups of donors. In one of these groups the number of PMN, RFC and adhering cells remained unchanged compared to the pre‐apheresis values. The other group showed marked leucocytosis accompanied by a relative increase in the number of non‐RFC and non‐adhering cells. Possible mechanisms involved in the changes of PMN subpopulations are discussed.
Globin chain synthesis ratios in sideroblastic anaemia
Authors: Peters Rowayda E. , May Alison , Jacobs Allan
Published: July 2010

Summary. Globin synthesis ratios were measured on reticulocytes from nine patients with primary acquired sideroblastic anaemia (SA), four patients with hereditary or congenital SA, two patients with secondary acquired SA and three patients with iron deficiency (ID). Ten of the samples from patients with SA and all the samples from patients with ID had normal ratios. Samples from three patients had significantly abnormal ratios, one from a patient with SA and acquired Hb H disease (α/β 0–26), one from a patient with secondary acquired SA (α/β 0–88), and one from a patient who went on to develop acute myeloblasts leukaemia (α/β 1–36). Globin synthesis was stimulated by 100 μ haem similarly in normal, SA and ID reticulocytes. Any limitation of globin synthesis in SA and ID is therefore not easily reversible by adding haem. Inhibition of haem synthesis in nonsideroblastic reticulocytes using 4 mM isonicotinic acid hydrazide for 1 h incubation affected neither total globin synthesis nor the α/β ratio. These results contradict the view that decreased haem synthesis decreases globin chain synthesis and decreases the α/β globin chain synthesis ratios in human reticulocytes. Previously reported findings that haem could reverse globin chain synthesis inhibition in SA were good evidence for a primary deficiency of haem synthesis in the erythroblasts of these patients. Our inability to substantiate these findings emphasizes the need for a re‐evaluation of the aetiology of sideroblastic anaemia.
A NEW DNA POLYMORPHISM IN THE β‐GLOBIN GENE CLUSTER CAN BE USED FOR ANTENATAL DIAGNOSIS OF β‐THALASSAEMIA
Authors: Old J. M. , Wainscoat J. S.
Published: July 2010

Summary. Restriction endonuclease analysis of the human β‐globin gene cluster has revealed a new DNA polymorphism at a Pvu II recognition site approximately 3.5 kilobases from the 3′ end of the Aγglobin gene. In patients from the Mediterranean area, the Pvu II polymorphism was associated equally with both normal and β‐thalassaemia chromosomes. In patients of Indian and Pakistani origin the polymorphism was almost exclusively associated with only the normal chromosome. Therefore this site may prove very useful for the antenatal diagnosis of β‐thalassaemia by acting as a genetic marker for the normal chromosome in linkage analysis of family members.
Arachidonic acid metabolism by platelets of differing size
Authors: Jakubowski Joseph A. , Thompson Craig B. , Vaillancourt Raymond , Valeri C. Robert , Deykin Daniel
Published: July 2010

Summary. The relationship between mean platelet volume (MPV) and platelet arachidonic acid metabolism was examined by studying the ability of human platelets of different size to incorporate and metabolize tritiated arachidonic acid ([3HIAA). Platelet phospholipids were labelled with [jH]AA and the platelets were then fractionated into size‐dependent subpopulations by counterflow centrifugation. The incorporation of [jH]AA increased through the fractions proportional to the MPV. After thrombin stimulation the per cent of total jH‐radioactivity released from the platelets decreased as the MPV increased. However, fractionation of the released %‐radioactivity by HPLC (high performance liquid chromatography) demonstrated that MPV had no significant influence on the per cent of total platelet 3H‐radioacti‐vity released as cyclooxygenase products or as HETE (12‐hydroxyeicosatetraenoic acid) but that the release of unmetabolized [3H]AA decreased as MPV increased. In separate experiments using unlabelled platelets the absolute release of thromboxane BL (TXB2) after collagen‐ and thrombin‐induced aggregation was measured by radioimmunoassay and was found to increase in proportion to the MPV. These results demonstrate that the release of arachidonic acid metabolites is qualitatively similar in platelets of different size. However, the absolute ability of platelets to incorporate arachidonic acid, convert it to active metabolites and release them is proportional to their volume. The ability of platelets to release unmetabolized arachidonic acid varies inversely with their MPV.
Iron loading in congenital dyserythropoietic anaemias and congenital sideroblastic anaemias
Authors: Cazzola Mario , Barosi Giovanni , Bergamaschi Gaetano , Dezza Laura , Palestra Pietro , Polino Grazia , Ramella Simona , Spriano Paolo , Ascari Edoardo
Published: July 2010

Summary. The relationship between body iron status, degree of anaemia, erythroid expansion, age and sex has been studied in eight patients with congenital dyserythropoietic anaemia (CDA) and two patients with congenital sideroblastic anaemia, who had received no or very few blood transfusions and no medicinal iron during the course of their illness. All patients had increased iron stores. Iron load was mild in three women in the reproductive age and severe in two men, in middle age, who had evidence of parenchymal organ dysfunction. Iron loading, as judged by the plasma ferritin concentration, was independent of the degree of anaemia while it was closely related to the patient's age and the degree of increase in the total erythropoietic activity. It is concluded that patients with CDA or congenital sideroblastic anaemia are at high risk of developing haemochromatosis in middle age. Prophylactic phlebotomy or iron chelation therapy should be considered for such patients.
Graft rejection following HLA matched T‐lymphocyte depleted bone marrow transplantation
Authors: Patterson J. , Prentice H. G. , Brenner M. K. , Gilmore M. , Janossy G. , Ivory K. , Skeggs D. , Morgan H. , Lord J. , Blacklock H. A. , Hoffbrand A. V. , Apperley J. F. , Goldman J. M. , Burnett A. , Gribben J. , Alcorn M. , Pearson C. , Mcvickei I. , Hann I. M. , Reid C. , Wardle D. , Gravett P. J. , Bacigalupo A. , Robertson A. A. G.
Published: July 2010

Summary. Bone marrow graft rejection following HLA‐matched bone marrow transplantation (BMT) for leukaemia has been a rare problem. However, with the introduction of T‐lymphocyte depleted BMT, graft rejection is recognized as a new complication. At the Royal Free Hospital (RFH) in London T‐depletion is achieved using two monoclonal antibodies with complement mediated lysis. The methodology was extended to other centres and in total 56 patients have received T‐depleted, HLA matched BMT. Twelve of 56 patients have had graft rejection. At the RFH three of 41 (7%) patients have had rejection whereas at collaborating centres nine of 15 (60%) patients have had rejection. We have investigated these rejections in order to identify factor(s) responsible. Rejection was not restricted by patient or donor characteristics, nor disease status. Patient management, chemotherapy conditioning, efficiency of T‐depletion, graft versus host disease (GvHD), and infection post BMT, were not consistently implicated. The major difference between the RFH and all other centres was in the radiotherapy (RT) conditioning: The RFH prescribed a single fraction of 7‐5 Gy total body irradiation (TBI) whilst collaborating centres gave 10 or 12 Gy fractionated TBI. We conclude that the different incidence of rejection (7% v. 60%) relates primarily to the RT conditioning although the mechanisms(s) of rejection remain unknown. We conclude that where T‐depleted BMT is used, compensation by more intensive RT conditioning is required in order to avert graft rejection.
Ultrastructure and cytogenetics in seven cases of acute promyelocytic leukaemia (APL)
Authors: Pearson E. C. , Matthews J. G. , Hayhoe F. G. J.
Published: July 2010

Summary. In the seven cases of acute promyelocytic leukaemia (APL) presented here we have studied the ultrastructural and cytogenetic features which are thought to be of particular significance in this disease. On the basis of our findings from the seven cases of APL described in detail, and our unreported results obtained for a large number of myeloid leukaemias other than APL, we conclude the following. Stellate rough endoplasmic reticulum, certain inclusion bodies and Auer rods having a tubular substructure are, if present, probably diagnostic of APL. However, these structures are not always observed in APL. Inflated rough endoplasmic reticulum is highly indicative of APL while slender cytoplasmic projections, convoluted or lobed nuclei and conspicuous bundles of cytoplasmic fibrils are very common in the abnormal promyelocytes of this disease. There is a strong correlation between the presence of conspicuous bundles of cytoplasmic fibrils and convoluted or lobed nuclei. Most of the APL cases showed the characteristic translocation t(15;17) and we could find no ultrastructural difference between the cases with the translocation and the single example of a normal karyotype.
Complement activation in vitro by antiplatelet antibodies in chronic immune thrombocytopenic purpura
Authors: Tsubakio T. , Tani P. , Curd J. G. , Mcmillan R.
Published: July 2010

Summary. Many chronic ITP patients have increased amounts of platelet‐associated IgG, C3, C4 and C9, suggesting in vivo complement activation. In this study, we assessed the ability of various antiplatelet antibodies (APA) to activate and deposit complement proteins and to cause platelet lysis in vitro. Platelet sensitization with rabbit APA, anti‐PlA1 antibody (one patient), anti‐HLA antibody (two patients) and ITP autoantibodies (four patients) resulted in the deposition of C4 and C3 onto platelets in an amount proportional to the quantity of antibody‐containing sera used to sensitize the platelets. Although C9 deposition onto platelets could not be quantitatively demonstrated on platelets sensitized with ITP serum, platelet lysis (51 Cr release) was noted after incubation with each of three ITP sera and complement. When compared, ITP autoantibodies, anti‐HLA and anti‐PlAi antibodies activated complement to a similar degree. We conclude that some autoantibodies in chronic ITP activate the classical complement pathway. The demonstration of in vitro platelet lysis by autoantibodies and complement suggests that in vivo platelet lysis may occur in some chronic ITP patients.