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Various kinds of surface modifications of titanium scaffolds have been attempted for the purpose of inducing their bone-bonding ability. Among them, chemical and heat treatments are simple, inexpensive, and easily applied uniformly, even for the inner surface of the pores of medical devices having a complex shape. In this chapter, some simple chemical and heat treatments that are effective for inducing bone-bonding as well as osteoconduction and osteoinduction are described.

A bioactive material is one that elicits a specific biological response at the interface of the material which results in the formation of a bond between the tissues and the material. A common characteristic of bioactive glasses, bioactive glass-ceramics, and bioactive ceramics is that their surface develops a biologically active hydroxy carbonate apatite (HCA) layer which bonds with collagen fibrils. The HCA phase that forms on bioactive implants is equivalent chemically and structurally to the mineral phase of bone. It is that equivalence which is responsible for interfacial bonding1–3.

Background and aim: Helicobacter pylori infection and gastric atrophy are both risk factors for gastric cancer. We aimed to elucidate the natural history of gastric cancer development according to H pylori infection and gastric atrophy status. Subjects and methods: A total of 9293 participants in a mass health appraisal programme were candidates for inclusion in the present prospective cohort study: 6983 subjects revisited the follow up programme. Subjects were classified into four groups according to serological status at initial endoscopy. Group A (n = 3324) had “normal” pepsinogen and were negative for H pylori antibody; group B (n = 2134) had “normal” pepsinogen and were positive for H pylori antibody; group C (n = 1082) had “atrophic” pepsinogen and were positive for H pylori antibody; and group D (n = 443) had “atrophic” pepsinogen and were negative for H pylori antibody. Incidence of gastric cancer was determined by annual endoscopic examination. Results: Mean duration of follow up was 4.7 years and the average number of endoscopic examinations was 5.1. The annual incidence of gastric cancer was 0.04% (95% confidence interval (CI) 0.02–0.09), 0.06% (0.03–0.13), 0.35% (0.23–0.57), and 0.60% (0.34–1.05) in groups A, B, C, and D, respectively. Hazard ratios compared with group A were 1.1 (95% CI 0.4–3.4), 6.0 (2.4–14.5), and 8.2 (3.2–21.5) in groups B, C, and D, respectively. Age, sex, and “group” significantly served as independent valuables by multivariate analysis. Conclusions: The combination of serum pepsinogen and anti- H pylori antibody provides a good predictive marker for the development of gastric cancer.

Ubiquitin carboxyl-terminal hydrolase-L1 (UCH-L1) is a restrictedly expressed enzyme in neural and reproductive tissues, and it is considered to have a significant role in reproduction. In the present study, we investigated the localization of UCH-L1 in placenta of cynomolgus monkeys (Macaca fascicularis). UCH-L1 protein was detected in cytotrophoblasts of chorionic plate and villi, and decidual cells of decidua basalis in cynomolgus monkey placenta, and the amount of UCH-L1 protein in whole placenta increased as pregnancy progressed. These results supported that UCH-L1 is necessary for placental and fetal development in primate placenta. This is the first report to demonstrate the presence of UCH-L1 in primate placenta, and the cynomolgus monkey may be a useful model for the study of the functions of the ubiquitin-proteasome system in human pregnancy.

Domain-specific Web search engines are effective tools for reducing the difficulty experienced when acquiring information from the Web. Existing methods for building domain-specific Web search engines require human expertise or specific facilities. However, we can build a domain-specific search engine simply by adding domain-specific keywords, called "keyword spices," to the user's input query and forwarding it to a general-purpose Web search engine. Keyword spices can be effectively discovered from Web documents using machine learning technologies. The paper describes domain-specific Web search engines that use keyword spices for locating recipes, restaurants, and used cars.

XPS analysis on single damascene (SD) patterned wafers was performed to study the modification of materials, especially the sidewall, during etching and strip. LKD-5109, MSQ-type materials (k≈2.2) were used as ILD, SiC/SiO2 as top hard mask (HM), and SiC as bottom liner. The etching in Ar/CF4/CH2F2/O2 creates a CFx polymer passivation layer on all patterned surfaces. The etched sidewall surface consists of two regions; a thin skin layer of CFx polymer and CF-rich SiOC layer behind. An N2/O2 strip removes CFx polymer and CF-rich layer efficiently (less than 1 at.% fluorine content). Instead of fluorine, CN-rich layers containing 11-20 at.% nitrogen were observed for all surfaces. After N2/O2 strip, the sidewall consists of two regions; a few nanometers of CN rich SiOC layer at the surface and several tens of nanometers of a C-depleted oxide type layer. N2/H2 strip provides a thinner C-depleting oxide type layer than either N2/O2 and CF4/O2 strips. However, the N2/H2 strip cannot eliminate fluorine contamination more than the N2/O2 strip.

Increasing the circuit density is driving the need for lower permittivity interlayer dielectrics (ILD) to reduce the capacitance between long parallel lines. JSR's LKD-5109, an MSQ-based material, is one of such low-k materials for the 65-nm node. The feasibility of integrating LKD-5109 in a single inlaid structure has been investigated. Thermal stability, chemical compatibility to stripping agents and CMP slurries are verified. A single damascene structure incorporating a dual CVD hard mask has been attempted and electrical results have been evaluated.

The 435 MHz beat signal between two modes of a He–Ne laser (633 nm) has been detected in the current of a scanning tunneling microscope (STM), using a silver probe to enhance the sensitivity using its plasmon resonance. The difference frequency between this optical beat and a radio frequency voltage applied to the junction has also been detected in the STM current. The difference frequency and heterodyne signals, as well as the direct current (dc) probe expansion, fit a calculation of modulated and dc thermal expansion of the probe tip, once one assumes that a surprisingly large fraction of the laser beam is absorbed at a small structure at the probe end. The beat signal due to current rectification is not observed for the experimental conditions, but the potential for utilizing the plasmon resonance to obtain such a signal using a silver probe is evaluated for other, feasible conditions where it might provide exceptional sensitivity.

We have devised a new in situ monitoring method for the amount of stratified compaction in borehole drilled several hundred meters underground. This newly developed epoch-making monitoring system differs from conventional monitoring methods for land subsidence in that it is designed to continuously monitor the amounts of displacement in several intervals separately, using optical fibers fitted in the sensor assembly. This report presents results from a deep observation well. This is a continued report from the previous one on EISOLS 2010.

Some ceramics bond to living bone through a bone-like apatite layer which is formed on their surfaces in the living body. The formation of the apatite layer is induced by SiOH or TiOH groups on their surfaces. These findings provide us with a biomimetic process with which to form a bone-like apatite layer on metals and organic polymers. Titanium metal and its alloys form a thin alkali titanate layer on their surfaces when they are subjected to alkaline solution and heat treatments. Thus, treated metals form a dense, uniform bone-like apatite layer on their surfaces in acellular simulated body fluid (SBF) with ion concentrations nearly equal to those of human blood plasma. Organic polymers form apatite nuclei on their surfaces when they are placed on CaOSiO2-based glass grains soaked in SBF. Thus, treated polymers form a dense, uniform bone-like apatite layer on their surfaces in SBF or other solutions highly supersaturated with respect to the apatite. The thickness of the apatite layer increases with increasing soaking time in the solution. The composition and structure of the apatite can be controlled by ion concentrations in the solution. The adhesive strengths of the apatite layer to the metal substrates are very high, and those to the polymer substrates can be considerably increased by glow discharge pretreatment of the substrates.

To study the pathophysiology of hyperlipidemia in nephrotic syndrome, we compared lipid metabolism in the nephrotic stage (stage 1) and in stage 2, when albuminuria had subsided, in 11 patients with minimal-change disease treated with corticosteroid. High-density lipoprotein (HDL) levels were decreased and HDL contained more cholesterol and triglyceride per unit of protein in stage 1 in the patients than in age-matched healthy controls. The urinary protein level was positively correlated only with low-density lipoprotein (LDL) levels, suggesting that the increased albumin clearance stimulated LDL production. Serum cholesterol levels were positively correlated with apolipoprotein E levels and were negatively correlated with lecithin-cholesterol acyltransferase activity in the nephrotic stage; the opposite correlations were seen in controls. Although triglycerides in HDL had normalized at stage 2, triglycerides in LDL and very-low-density lipoprotein did not return toward normal until stage 3, when serum cholesterol levels were normalized.

Computer-aided detection/diagnosis (CAD) is emerging as an innovative interdisciplinary technology for medical service. The traditional concept of automated computer diagnosis is encountered with a significant barrier because computerized medical systems cannot fully replace human doctors with the comparable level of performance. By contrast, CAD is becoming widely adopted in clinical work because it offers complementary computing power to enhance doctor's competence for medical examination. 4 state-of-the-art CAD technologies were presented in the special session of medical image processing and CAD at ICCH 2012 as reported in this short paper. Those technologies will be briefly introduced here to show the current trend of development of CAD and to demonstrate how CAD helps in medical care.

ObjectivesThe aim of the study is to determine factors affecting ischaemic wound healing and role of the angiosome concept in bypass surgery.DesignSingle-centre, retrospective clinical study.Materials and methodsA total of 249 consecutive critical ischaemic limbs with tissue loss in 228 patients who underwent distal bypasses from 2003 to 2009 were reviewed. A total of 81% of patients were diabetic, and 49% of patients had dialysis-dependent renal disease (end-stage renal disease, ESRD). Distal targets of bypasses were the crural artery (57%) and the pedal artery (43%).ResultsThe complete healing of ischaemic wounds was achieved in 211 limbs (84.7%). ESRD (odds ratio (OR) 0.127, p

Bioactive layers, which induce apatite formation on their surfaces in the living body and bond to living bone through this apatite layer, can be formed on various kinds of metals and polymers by simple chemical and heat treatments. They are easily and uniformly formed even on irregular inner surfaces of porous materials. Their functions can be varied by incorporating different ions into the bioactive layers through the chemical treatments. Metals and organic polymers formed with these novel bioactive layers on their surfaces are used in various applications in the orthopedic and dental fields, such as hip and knee joints, spinal fusion devices, and dental implants, because of their high fracture toughnesses and ductility, properties that are lacking in bioactive ceramics, as well as high bioactivities. Formation of different kinds of bioactive layers on metals and polymers by various methods, and the structure, properties, and clinical applications of the resultant products are reviewed in this chapter.

This study investigated the in vitro effects of bioactive titanium surfaces on osteoblast differentiation. Three titanium substrates were tested: a commercially pure titanium (Cp Ti), an alkali- and heat-treated titanium (AH Ti), and an apatite-formed titanium (Ap Ti) generated by soaking AH Ti in a simulated body fluid. Chemical evaluation of the surface reactivity was analysed at nanometre scale by X-ray photoelectron spectroscopy (XPS), and at micrometre scale by energy dispersive X-ray microanalysis (EDX). It showed that the estimated proportion of the surface covered by adsorbed serum proteins differed between the three substrates and confirmed the bioactivity of AH Ti, illustrated by surface calcium and phosphate deposition when immersed in biological fluids. Mouse calvaria osteoblasts were cultured on the substrates for 15 days with no sign of cytotoxicity. Enzyme immunoassay and Real-Time RT-PCR were used to follow osteoblast differentiation through the production of osteocalcin (OC) and expression of several bone markers. At day 15, a significant up-regulation of Runx2, Osx, Dlx5, ALP, BSP, OC and DMP1 mRNA levels associated with an increase of OC production were observed on AH Ti and Ap Ti when compared to Cp Ti. These results suggest that bioengineered titanium has a great potential for dental applications in enhancing osseointegration.

The radio frequency glow discharge in Ar at 13.56 MHz has been investigated by using time- and space-resolved emission spectroscopy with a resolution of 0.2 ns. The relative net excitation rate is also obtained by deconvoluting the emission profile considering the effect of the lifetime. From these results, the authors are able to guess the electron transport and the temporal structure of the discharge. ArI(3p5 to 1s4), ArI(2p2 to 1s5) and ArII(4p4D7/2 to 4s4P5/2) lines are selected for observation. The electrons with low energy, epsilon >14.57 eV, are transported corresponding to the phase of the current. The electrons with higher energy, M>35.05 eV, are observed at the phase corresponding to the applied voltage only when the aluminium electrode is used under the present experimental conditions. It is confirmed that the high-energy electrons are secondary electrons emitted from the electrode. The RF discharge in Ar at 13.56 MHz has two modes with a hysteresis loop as the function of input energy.

Lung volume reduction surgery (LVRS) is performed as surgical therapy for severe pulmonary emphysema. In assessing diagnostic imaging indications, emphysematous change is the strongest in the thoracic computed tomography (CT), while the accumulation decrease is most remarkable in ventilation scintigram and lung perfusion scintigram. Preoperative evaluation of imaging using multidetector-row CT (MDCT) and scintigram were performed, and the multiplanar reconstruction (MPR) image of the MD CT and the single photon emission CT (SPECT) image of the scintigram were fused by the workstation. It was possible to evaluate the excision and the range of LVRS easily by looking at the fused image, and it was useful in deciding on the surgical approach. It is believed that accurate, comprehensible imaging information contributed to an improvement in the surgical outcome of LVRS.

The spread and progress of thoracoscopic surgery has been remarkable. There are many important organs and blood vessels in the mediastinal space, thus, as inadvertent injury invites serious consequences, it is necessary to understand the anatomical position of existing structures. When enucleating the thymoma under a thoracoscope, one of the blood vessels to be careful about is the thymic vein. Therefore, we examined whether the thymic vein could be confirmed using a multidetector-row computed tomography (MD CT). We believed we could understand the anatomical position of the thymic vein by analyzing the high resolution slice data provided in MD CT using a work station. The diameter of the thymic is from a little less than 1 mm to 3 mm, and there were individual variations in position and the number of the vein. The thymic vein flowed into the left brachiocephalic vein in many cases. In some cases, the thymic vein flowed into the right internal thoracic vein or superior vena cava. It appears that visualization of the thymic vein could provide useful data when performing thoracoscopic thymectomy.

One-lung anesthesia is a method of anesthesia performed by inserting the tip of a bronchial tube into either the right main bronchus or the left main bronchus. The right bronchial tube is a special structure. Since the distance of the carina to the right upper lobe bronchus is short, a side hole is made to prevent blockading of the right upper lobe bronchus, and the cuff is attached aslant to it. When inserting a bronchial tube into the right main bronchus, care is required to prevent the occurrence of atelectasis though a gap in the bronchial tube. We evaluated the structure of a trachea and a bronchus using the multidetector-row computed tomography (MD CT), and tried to select the right bronchial tube most suitable for each structure. There are individual differences in the structure of a trachea and a bronchus. By creating a 3-dimensional image of a trachea and a bronchus, the structure could be easily grasped, and therefore selection of the most appropriate bronchial tube according to the structure was possible.

To achieve effective k value less than 3.0, we investigated spin-on dielectric stack damascene integration scheme with electron beam (EM) cure. By using porous-MSQ (k=2.3) as ILD and dense-MSQ (k=2.9) as hard mask (HM), effective k value could be lowered, and by EB curing the full dielectric stack only once, mechanical strength for both ILD and HM were improved and a reduced thermal budget was obtained. In addition, a low damage resist strip process for the low-k materials was evaluated. These elements of BEOL technology have applicability to 45nm technology node and beyond.

Metallic materials implanted into bone defects are generally encapsulated by a fibrous tissue. Some metallic materials such as titanium and tantalum, however, have been revealed to bond to the living bone without forming the fibrous tissue, when they were subjected to NaOH solution and heat treatments. Thus treated metals form bone tissue around them even in muscle, when they take a porous form. This kind of osteoconductive and osteoinductive properties are attributed to sodium titanate or tantalate layer on their surfaces formed by the NaOH and heat treatments. These layers induce the deposition of bonelike apatite on the surface of the metals in the living body. This kind of bioactive metals are useful as bone substitutes even highly loaded portions, such as hip joint, spine and tooth root.

A dense and uniform layer of highly bioactive apatite can be formed in arbitrary thickness on any kind and shape of organic polymer substrates by the following biomimetic process. The substrate is first placed in contact with granular particles of CaO, SiO2-based glass soaked in a simulated body fluid with ion concentrations nearly equal to those of human blood plasma for forming apatite nuclei, and then soaked in another fluid highly supersaturated with respect to the apatite for making the apatite nuclei grow. In the present study, the polymer substrates were pretreated with ultraviolet (UV) light, and then subjected to the biomimetic process described above. By UV irradiation, the induction period for the apatite nucleation of poly(ethylene terephthalate) (PET), poly-ether sulphone (PESF), polyethylene (PE), poly(methyl methacrylate) (PMMA) and polyamide 6 (N6) substrates were reduced form 24 h to 10 h. The adhesive strengths of the apatite layer to the substrates increased from 2.5-3.2 MPa to 4.5-6.0 MPa for PET, PESF and PMMA, and from about 1.0 MPa to 4.0-6.5 MPa for PE and N6 substrates. These results have been explained by assuming that silicate ions, which induce apatite nucleation, are easily adsorbed on the substrates due to the formation of polar groups, with an improved hydrophilic nature, on the polymer surfaces by UV irradiation.

The bioactivity of a range of glass-ceramic apatite-wollastonite (A-W) - polyethylene composites (AWPEXs) with glass-ceramic A-W volume percentages ranging from 10 to 50, has been investigated in an acellular simulated body fluid (SBF) with ion concentrations similar to those of human blood plasma. The formation of a biologically active apatite layer on the composite surface after immersion in SBF was demonstrated by thin-film X-ray diffraction (TF-XRD) and field-emission scanning electron microscopy (FE-SEM). An apatite layer was formed on all the composites, with the rate of formation increasing with an increase in glass-ceramic A-W percentage. For composites with glass-ceramic A-W filler contentsor=30 vol %, the apatite layer was formed within 12 h of immersion, which is a comparable time for apatite formation on monolithic glass-ceramic A-W. Inductively coupled plasma atomic emission spectroscopy (ICP-AES) demonstrated that the apatite formation on AWPEX samples with 50 vol % filler content occurred in a manner similar to that seen on pure glass-ceramic A-W, in that the calcium, silicon, and magnesium ion concentrations increased and, conversely, a decrease was observed in the phosphate ion concentration. These results indicate that a suitable in vitro response was achieved on a composite incorporating particulate glass-ceramic A-W with a particularly favorable response being observed on the AWPEX sample with 50 vol % filler content.

It has been confirmed that the apatite nucleation is induced by silanol (Si-OH) groups formed on the surfaces of materials and/or silicate ions adsorbed on them. It was previously shown that apatite nuclei are formed on organic polymers when the polymers are placed on CaO, SiO2-based glass particles soaked in a simulated body fluid (SBF) with ion concentrations nearly equal to those of human blood plasma, and that they grow spontaneously to form a dense and uniform apatite layer together with high adhesive strength to the substrates when the polymers are soaked in another solution with ion concentrations 1.5 times the SBF. In the present study, silanol groups bonded covalently to the surface of the silicone substrate were formed and its apatite-forming ability was examined. When silicone substrates were treated with 5 or 10 M NaOH with pH 7.25 at 36.5 degrees C for more than 3 h, silanol groups were formed on the surfaces of the substrates. When thus NaOH-treated substrates were soaked in 1.5SBF at 36.5 degrees C, a bone-like apatite was formed on the substrates in a short period.

The prerequisite for an artificial material to bond to living bone is the formation of bonelike apatite on its surface in the body. This apatite can be reproduced on its surface even in an acellular simulated body fluid with ion concentrations nearly equal to those of the human blood plasma. The present authors previously showed that the tantalum metal subjected to a NaOH treatment to form a sodium tantalate hydrogel layer on its surface forms the bonelike apatite on its surface in SBF in a short period. The gel layer as-formed on the metal is, however, not resistant against abrasion, and hence thus-treated metal is not useful for clinical applications. In the present study, effects of thermal treatment on the mechanical properties and apatite-forming ability of the NaOH-treated tantalum metal were investigated. The sodium tantalate gel on the NaOH-treated tantalum was dehydrated to convert into amorphous sodium tantalate by a thermal treatment at 300 degrees C in air environment and into crystalline sodium tantalates by the thermal treatment at 500 degrees C. Resistivity of the gel layer against both peeling-off and scratching was significantly improved by the thermal treatment at 300 degrees C. The high apatite-forming ability of the sodium tantalate hydrogel was a little decreased by the thermal treatment at 300 degrees C, but appreciably decreased by the thermal treatment at 500 degrees C. It is believed that the tantalum metal subjected to the 0.5 M-NaOH treatment and the subsequent thermal treatment at 300 degrees C is useful as implants in dental and orthopaedic fields, since it shows high bioactivity as well as high fracture toughness.

A chemically durable glass microsphere containing a large amount of phosphorus is useful for in situ irradiation of cancers, since they can be activated to be a beta-emitter with a half-life of 14.3 d by neutron bombardment. When the activated microspheres are injected to the tumors, they can irradiate the tumors directly with beta-rays without irradiating neighboring normal tissues. In the present study, P+ ion was implanted into silica glass microspheres of 25 microm in average diameter at 50 keV with nominal doses of 2.5 x 10(16) and 3.35 x 10(1)6 cm(-2). The glass microspheres were put into a stainless container and the container was continuously shaken during the ion implantation so that P+ ion was implanted into them uniformly. The implanted phosphorus was localized in deep regions of the glass microsphere with the maximum concentration at about 50 nm depth without distributing up to the surface even for a nominal dose of 3.35 x 10(16) cm(-2). Both samples released phosphorus and silicon into water at 95 degrees C for 7 d. On the basis of the previous study on P+-implanted silica glass plates, the silica glass microspheres containing more phosphorus which is desired for actual treatment could be obtained, without losing high chemical durability, if P+ ion would be implanted at higher energy than 50 keV to be localized in deeper region.

Apatite layer was formed on polyethyleneterephthalate (PET) substrate by the following biomimetic process. The PET substrate was placed on granular particles of a CaO, SiO2-based glass in simulated body fluid (SBF) with ion concentrations nearly equal to those of human blood plasma to form apatite nuclei on their surfaces. The apatite nuclei was then grown into a continuous layer by subsequently soaking the substrate in SBF under air or CO2 atmosphere in which CO2 partial pressure in the ambient was adjusted to 14.8 kPa to increase the content of carbonate ion to a level nearly equal to that of blood plasma. The increase in the content of carbonate ions in SBF changed the Ca/P atomic ratio of the apatite from 1.51 to 1.63, content of CO(3)2- ions from 2.64 to 4.56 wt %, and lattice constants a from 94.32 to 94.23 nm and c from 68.70 to 68.83 nm, respectively. The Ca/P ratio and lattice constants of the apatite formed in SBF under CO2 atmosphere were approximately identical to those of bone apatite, i.e. Ca/P atomic ratio 1.65, content of CO(3)2- ion 5.80 wt % and lattice constants a 94.20 and c 68.80 nm. This indicates that an apatite with composition and structure nearly identical to those of bone apatite can be produced in SBF by adjusting its ion concentrations including the content of carbonate ions to be equal to those of blood plasma.

Polydimethylsiloxane (PDMS)-CaO-SiO(2) hybrids with starting compositions containing PDMS/(Si(OC(2)H(5))(4)+PDMS) weight ratio=0.30, H(2)O/Si(OC(2)H(5))(4) molar ratio=2, and Ca(NO(3))(2)/Si(OC(2)H(5))(4) molar ratios=0-0.2, were prepared by the sol-gel method. The apatite-forming ability of the hybrids increased with increasing calcium content in the Ca(NO(3))(2)/Si(OC(2)H(5))(4) molar ratio range 0-0.1. The hybrids with a Ca(NO(3))(2)/Si(OC(2)H(5))(4) molar ratio range 0.1-0.2 formed apatite on their surfaces in a simulated body fluid (SBF) within 12 h. The hybrid with a Ca(NO(3))(2)/Si(OC(2)H(5))(4) molar ratio of 0.10 showed an excellent apatite-forming ability in SBF with a low release of silicon into SBF. It also showed mechanical properties analogous to those of human cancellous bones. This hybrid is expected to be useful as a new type of bioactive material.

An Al- and V-free sodium titanate hydrogel layer with a graded structure where the sodium titanate gradually decreases toward the interior, was formed on the surface of Ti-6Al-4V alloy, when the alloy was exposed to 5M NaOH solution at 60 degrees C for 24 h. This gel layer was transformed into an amorphous sodium titanate layer without giving considerable change in the graded structure, except a little increase in the depth of the oxygen distribution by a heat treatment at 600 degrees C for 1 h. The sodium titanate layer formed Ti-OH groups on its surface by exchanging its Na+ ion with H3O+ ion in simulated body fluid when soaked in the fluid, and thus formed Ti-OH groups induced the apatite nucleation. The apatite layer also formed a graded structure toward the substrate. The strong bond of the apatite layer to the substrate was attributed to this graded structure.

Tantalum metal is a candidate for use as an implant material in high load-bearing bony defects, due to its attractive features such as high fracture toughness and high workability. This metal, however, does not have bone-bonding ability, i.e. bioactivity, and therefore the development of bioactive tantalum metal is highly desirable. It is known that the essential prerequisite for an artificial material to show bioactivity is to form a bonelike apatite layer on its surface in the body environment. The same type of apatite layer is formed in a simulated body fluid (SBF) with inorganic ion concentrations nearly equal to those of human blood plasma. The present authors previously showed that the apatite formation on tantalum metal in SBF was remarkably accelerated by treatment with 0.5 M-NaOH aqueous solution and subsequent firing at 300 degrees C, while untreated tantalum metal spontaneously formed the same apatite after a long soaking period. In the present study, the bonding strength of the apatite layer to the substrate was quantitatively evaluated in comparison with that to the untreated tantalum metal. Adhesive strength was measured as an estimation of bonding strength, and the surface microstructure of both the substrates was characterized in order to discuss the difference in the bonding strength in terms of surface structure. The apatite layer formed on the NaOH- and heat-treated tantalum metal shows higher adhesive strength than that formed on the untreated metal. The amorphous sodium tantalate layer formed on the tantalum metal by NaOH and heat treatments, has a smooth graded structure where its concentration gradually changes from the surface into the interior metal. Smooth graded structure with complex of apatite is constructed after soaking in SBF. The higher bonding strength of the apatite layer formed on the treated metal is attributed to its smooth graded structure.

The effect of the amount of a water-soluble, lactose, on cephalexin (CEX) release from bioactive bone cement consisting of bisphenol-alpha-glycidyl methacrylate (bis-GMA), triethylene-glycol dimethacrylate (TEGDMA) resin and apatite- and wollastonite-containing glass-ceramic (A-W GC) powder was investigated. A-W GC powder containing 5% CEX and lactose powders hardened within 5 min after mixing with bis-GMA/TEGDMA resin, and furthermore its compressive strength was expected to be higher than that of polymethylmethacrylate cement. In vitro CEX release from bioactive bone cement pellets in a simulated body fluid at pH 7.25 and 37 degrees C continued for more than 2 wk. The drug-release rate increased with increasing amount of lactose powder in the mixture. CEX release profiles followed the Higuchi equation in the initial stage, but not in later stages. As hydroxyapatite was precipitated out on the cement surface, the CEX release rate decreased. The micropore distribution of the cements measured by mercury porosimetry also supported the variation in drug release due to cement porosity being mainly a result of the dissolution of lactose in the cements. These results suggest that the rate of CEX release from bioactive bone cement could be controlled by varying the amount of lactose in the cement system.

Crack- and pore-free transparent monolithic disks of polydimethylsiloxane (PDMS)- modified CaO-SiO2-TiO2 hybrids were obtained by hydrolysis and polycondensation of PDMS, tetraethoxysilane, tetraisopropyltitanate and calcium nitrate. The product as-dried at 60 degrees C formed an apatite on its surface in a simulated body fluid (SBF) within only one day, indicating its high bioactivity. The apatite-forming ability decreased slightly by a heat treatment below 250 degrees C. The bending strength of the product was about 11 MPa, independent of the heat treatment. This average strength value is comparable to that of the human cancellous bone. Young's modulus of the products increased from 100 to 500 MPa with increasing heat treatment temperature from 60 to 250 degrees C, but its values were within the range of those of the human cancellous bone. The strain at failure of the products decreased with increasing heat treatment temperature. Failure strains went down to the magnitudes exhibited by the human cancellous bone, when the products were heat treated in the temperature range from 150 to 250 degrees C. Thus, highly bioactive hybrids with mechanical properties analogous to those of the human cancellous bone were obtained. This new kind of bioactive hybrid may be useful as a bone-repairing material.

Some ceramics, such as Bioglass, sintered hydroxyapatite, and glass-ceramic A-W, spontaneously form a bone-like apatite layer on their surface in the living body, and bond to bone through the apatite layer. These materials are called bioactive ceramics, and are clinically important for use as bone-repairing materials. However, they cannot be used at high-load sites, such as is found in femoral and tibial bones, because their fracture toughness values are not as high as that of human cortical bone. Titanium metal and its alloys have high fracture toughness, and form a sodium titanate layer on its surface when soaked in a 5 M-NaOH solution at 60 degrees C for 24 h, followed by a heat treatment at 600 degrees C for 1 h. On moving toward the metal interior, the sodium titanate layer gradually changes into the pure metal within a distance of 1 microm from the surface. The mechanical strength of the titanium metal or a titanium alloy is not adversely affected by these chemical and thermal treatments. The titanium metal and its alloys resulting from the above treatment can release Na+ ions from its surface into a surrounding body fluid via an ion exchange reaction with H3O+ ions, resulting in many Ti-OH groups forming on its surface. These Ti-OH groups initially combine with Ca2+ ions to form amorphous calcium titanate in the body environment, and later the calcium titanate combines with phosphate ions to form amorphous calcium phosphate. The amorphous calcium phosphate eventually transforms into bone-like apatite, and by this process the titanium metals are soon tightly bonded to the surrounding living bone through the bone-like apatite layer. The treated metals have already been subjected to clinical trials for applications in artificial total hip joints. Metallic tantalum has also been found to bond to living bone after it has been subjected to the NaOH and heat treatment to form a sodium tantalate layer on its surface.

The feasibility of integrating low-k spin-on dielectrics into a Cu damascene structure using JSR's LKD-5109 (k = 2.2) has been investigated. The chemical vapor deposited embedded etch-stop (ES) and dual hard-mask (HM) are replaced by JSR's spin-on dielectrics (organic FF-02 and MSQ type LKD-2022). In this study, the capability of FF-02 as an ES and as a chemical mechanical polishing (CMP) stop has been verified. In addition to electrical and mechanical film properties of FF-02, the chemical compatibility and removal rate to CMP slurries are investigated. Finally, the first successful single damascene (SD) integration with spin-on dual HM and ES is demonstrated and its electrical results including Raphael's model simulation of the k-value are reported.

In this article the dual damascene (DD) patterning has been examined for a full spin-on stack of a low-K material in K-value of 2.2 generation, i.e. LKD-5109 with dual low-K spin-on hard masks (SoHM). Compared to conventional CVD-deposited dual hard masks (dHM), the top spin-on HM has a wider range of thickness for which standing waves in the resist can be prevented. Furthermore, an etch selectivity has been obtained of more than 30 for LKD-5109 towards organic SoHM using fluorocarbon chemistries. Through the design of dHM structure and etch process development, it was possible to reduce the number of steps using an in-situ resist ash and organic SoHM strip during etching. A DD 0.2 /spl mu/m trench/via structure was successfully etched.

In this paper, a system with "multi-base-station in a cell" using single frequency network (SFN) orthogonal frequency division multiplex (OFDM) is proposed as a basic concept of the 4th generation mobile system (4G). The proposed system image consists of several cells in a larger cell and it works as follows: first, a sub-base station (S-BS) is set to transmit partially at the place where the received signal power is below the desired one, because of increase of path loss while operating at high frequency, and under shadowing; secondly, base stations (BSs) and S-BSs transmit the same information at the same time by SFN-OFDM, so paths having in good condition may exist. However, at a receiver the timing offset in arrival between paths of BSs and S-BSs leads to inter-symbol interference (ISI) which is the largest considerable problem. So a "transmission delay control" scheme using position information from the Global Positioning System (GPS) is also proposed. We discuss the usefulness of the proposed system against path loss increase and shadowing, and furthermore confirm that the proposed scheme is effective in operation at high speed rate.

We have developed a bioactive bone cement that consists of apatite and wollastonite containing glass-ceramic (AW-GC) powder and bisphenol-a-glycidyl dimethacrylate (Bis-GMA)-based resin. In this study, we made three types of composite (designated AWC, HAC, and TCPC) consisting of AW-GC, hydroxyapatite (HA,) or beta-tricalcium phosphate (beta-TCP) powder as the inorganic filler and Bis-GMA-based resin as the organic matrix. The proportion by weight of the filler mixed into the cement was 70%. Rectangular plates (10 x 15 x 2 mm) of each composite were made and abraded with 2000 alumina powder. These composites were implanted into tibial metaphyses of rabbits. Specimens were prepared 10 and 25 weeks after implantation and examined using transmission electron microscopy (TEM). AWC was in direct contact with bone 10 weeks after implantation, and AW-GC particles were partially absorbed at the surface. HAC was in contact with partially mineralized extracellular matrix 10 weeks after implantation. In TCPC-implanted specimens, randomly oriented mineral was observed 10 weeks after implantation; however, collagenous extracellular matrix rarely was observed. In 25-week specimens, AW-GC particles were completely absorbed and replaced by new bone, and there was no intervening soft tissue. Both HAC and TCPC were in contact with bone at 25 weeks. These results indicate that AWC has higher bioactivity than either HAC or TCPC.

The purpose of this study was to elucidate the effect of amount of ceramic cement powder on drug release from bioactive bone cement. The associated bone-bonding strength was also investigated. The bioactive bone cement under investigation consisted of bisphenol-alpha-glycidyl methacrylate (Bis-GMA), triethylene-glycol dimethacrylate (TEGDMA) resin and a combination of apatite- and wollastonite-containing glass-ceramic (A-W GC) powder. A-W GC powder (50%, 70% and 80% w/w) containing 5% cephalexin (CEX) powder hardened within 5 min after mixing with Bis-GMA/TEGDMA resin. The compressive strength of the cement with or without drug increased with increasing the amount of ceramic powder. The compressive strength of the 80% ceramic cement without the incorporation of cephalexin was 194 MPa. This compressive strength was about 3 times higher than that for polymethylmethacrylate cement. After the cement was implanted in the proximal metaphysis of the tibiae of male rabbits, the failure load for the cement was found to increase with increasing of the amount of ceramic powder. This finding suggested that the cement formed a bonding with bone. In vitro CEX release from bioactive bone cement pellets in a simulated body fluid at pH 7.25 and 37 degrees C continued for more than 2 weeks. Drug release profile followed the Higuchi equation initially, but not at later stages. The drug release rate increased with increasing amount of ceramic powder in the mixture. Since the pore volume of the cement increased with increasing of amount of ceramic powder, the drug diffused in the pores between the ceramics particle and polymer matrix. As hydroxyapatite precipitated on the cement surface, the drug release rate decreased, as observed at the later release stage. These results suggest that varying the amount of ceramic powder in the cement system could control the drug release rate from bioactive bone cement.

The possibility of safe implementation of neoadjuvant chemotherapy using nedaplatin (254-S) was investigated with the aim of improving the therapeutic results in advanced esophageal cancer patients. The subjects had usually undergone two courses of 254-S, 80 or 100 mg/m2, preoperatively, at intervals of 4 weeks. After chemotherapy, responses were evaluated, and resection was undertaken 4 weeks after the final administration. The subjects were 10 patients with untreated esophageal cancer. As a result of evaluation of responses of main lesions to chemotherapy, a partial response (PR) was observed in 3 patients, and a minor response 3, showing an efficacy rate of 30%. Pathological findings before treatment were determined by staining of a cell cycle marker (Ki-67). The 3 patients who were evaluated as PR (clinical efficacy) showed high rates of positivity for Ki-67 of 47.4%, 52.7%, and 86%, respectively. There were no serious complications and no death related to operation. The observations suggested that 254-S, which has little or no side effects including nephrotoxicity, can become the standard remedy for esophageal cancer instead of CDDP in future.

In this study we have investigated the behavior of fetal rat osteoblasts, cultured up to 23 days, on a bioactive apatite-wollastonite (AW) glass-ceramic and on the same material on which a carbonated apatite layer had been formed by a biomimetic process (AWa). At the last day of culture, the specific activity of alkaline phosphatase activity, as determined biochemically, was about 30% greater on AWa compared with AW disks. After the cell layers had been scraped off, scanning electron microscopic (SEM) observations of the materials' surfaces revealed that mineralized bone nodules remained attached to both surfaces but in larger amounts on AWa. X-ray microanalysis indicated the presence of calcium (Ca) and phosphorus (P) in the bone tissue throughout the AWa surface and Ca, P, and silicon (Si) on the AW surface. The AW/ and AWa/bone interfaces also were analyzed after fracturing of the disks. The interfacial analysis showed firm bone bonding to the AW and AWa surfaces, confirmed by the X-ray microanalytic mappings. These results indicate the importance of surface composition in supporting differentiation of osteogenic cells and the subsequent apposition of bone matrix, which allows a strong bond of the bioactive materials to the bone. Furthermore, prefabrication of a biologic apatite layer by a method that mimics biomineralization could find application to bone-repairing materials.

Under high shear stress, the binding of von Willebrand factor (VWF) A1-loop domain to platelet glycoprotein (GP) Ib alpha occurs as the earliest event in thrombus formation. Therefore recombinant VWF A1-loop fragments could be of therapeutic use in blocking this interaction as competing ligands. We have prepared three homodimeric VWF A1-loop fragments [315 kD Fr III (a homodimer of amino acid [aa] residues 1-1365 of the subunit), 220 kD Fr (a homodimer of aa residues 1-708 of the subunit), and 116 kD Fr (a homodimer of aa residues 449-728 of the subunit) and two monomeric fragments [39/34 kD Fr (a monomer of aa residues 480/481-718 of the subunit] and His-rVWF465-728 (a monomer of aa residues 465-728 of the subunit)], and assessed their potency as inhibitors of botrocetin-induced VWF binding to GPIb alpha and high shear stress induced platelet aggregation mediated by intact VWE All these fragments completely inhibited botrocetin-induced VWF binding to GPIb alpha at a final concentration of 40-200 microM. The homodimeric A1-loop fragments also totally inhibited high shear stress induced platelet aggregation at a final concentration of 0.45-2.0 microM in the following order: 315 kD Fror = 220 kD Fr116 kD Fr. In contrast, the monomeric A1-loop fragments were only partial inhibitors of high shear stress induced platelet aggregation even at a final concentration of 20 microM, and their IC50s were 13-39 times higher than those of the homodimers. These results indicate that the homodimeric structure of the A1-loop fragment is important for optimal molecular interaction with GPIb alpha under high shear stress.