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Background: A growing body of evidence suggests that non-viral hepatocellular carcinoma (HCC) might benefit less from immunotherapy. Materials and methods: We carried out a retrospective analysis of prospectively collected data from consecutive patients with non-viral advanced HCC, treated with atezolizumab plus bevacizumab, lenvatinib, or sorafenib, in 36 centers in 4 countries (Italy, Japan, Republic of Korea, and UK). The primary endpoint was overall survival (OS) with atezolizumab plus bevacizumab versus lenvatinib. Secondary endpoints were progression-free survival (PFS) with atezolizumab plus bevacizumab versus lenvatinib, and OS and PFS with atezolizumab plus bevacizumab versus sorafenib. For the primary and secondary endpoints, we carried out the analysis on the whole population first, and then we divided the cohort into two groups: non-alcoholic fatty liver disease (NAFLD)/non-alcoholic steatohepatitis (NASH) population and non-NAFLD/NASH population. Results: One hundred and ninety patients received atezolizumab plus bevacizumab, 569 patients received lenvatinib, and 210 patients received sorafenib. In the whole population, multivariate analysis showed that treatment with lenvatinib was associated with a longer OS [hazard ratio (HR) 0.65; 95% confidence interval (CI) 0.44-0.95; P = 0.0268] and PFS (HR 0.67; 95% CI 0.51-0.86; P = 0.002) compared to atezolizumab plus bevacizumab. In the NAFLD/NASH population, multivariate analysis confirmed that lenvatinib treatment was associated with a longer OS (HR 0.46; 95% CI 0.26-0.84; P = 0.0110) and PFS (HR 0.55; 95% CI 0.38-0.82; P = 0.031) compared to atezolizumab plus bevacizumab. In the subgroup of non-NAFLD/NASH patients, no difference in OS or PFS was observed between patients treated with lenvatinib and those treated with atezolizumab plus bevacizumab. All these results were confirmed following propensity score matching analysis. By comparing patients receiving atezolizumab plus bevacizumab versus sorafenib, no statistically significant difference in survival was observed. Conclusions: The present analysis conducted on a large number of advanced non-viral HCC patients showed for the first time that treatment with lenvatinib is associated with a significant survival benefit compared to atezolizumab plus bevacizumab, in particular in patients with NAFLD/NASH-related HCC.

Background Aortic dissection (AD) is a fatal disease where the intimomedial layer of the aorta suddenly fail. Although it is widely accepted that hemodynamic stress on the aortic wall triggers its destruction that is further promoted by inflammatory response as exemplified by the infiltration of neutrophils and macrophages, molecular mechanism is unknown for the link of aortic wall stress, inflammation and tissue destruction. In general, mechanical stress to the tissue is converted to the cellular response through the cell adhesion molecules and the activation of focal adhesion kinase (Fak). Although it has been reported that Fak is involved in pathogenesis of aortic aneurysm by promoting migration and activation of macrophages, its role in AD is unknown. We hypothesized that Fak may be involved in AD pathogenesis. Purpose We investigated the involvement of Fak in AD pathogenesis, focusing on its role in inflammatory cells. Methods and results We created a mouse model of AD by continuous infusion of beta-aminopropionitrile, a collagen crosslink inhibitor, and angiotensin II (BAPN + Ang II). Immunostaining for activated Fak revealed that Fak was not activated in normal aorta, but was activated in the infiltrating inflammatory cells and in interstitial cells of the aortic wall after AD development. We examined the role of Fak by oral administration of PND-1186, a specific Fak inhibitor, in mouse AD model. Vehicle-treated group showed 63.6% mortality, whereas PND-1186-treated group showed 20% mortality (P Conclusions These findings proved that Fak plays a critical role in AD progression and death. Because Fak is dispensable for macrophages and granulocytes, other cell types, possibly aortic wall interstitial cells, may be regulated by Fak in AD pathogenesis. Deciphering the role of Fak would provide the fundamental understanding of AD pathogenesis. Funding Acknowledgement Type of funding sources: None.

Background & aims: Genome-wide association studies in primary biliary cholangitis (PBC) have failed to find X chromosome (chrX) variants associated with the disease. Here, we specifically explore the chrX contribution to PBC, a sexually dimorphic complex autoimmune disease. Methods: We performed a chrX-wide association study, including genotype data from 5 genome-wide association studies (from Italy, United Kingdom, Canada, China, and Japan; 5244 case patients and 11,875 control individuals). Results: Single-marker association analyses found approximately 100 loci displaying P < 5 × 10-4, with the most significant being a signal within the OTUD5 gene (rs3027490; P = 4.80 × 10-6; odds ratio [OR], 1.39; 95% confidence interval [CI], 1.028-1.88; Japanese cohort). Although the transethnic meta-analysis evidenced only a suggestive signal (rs2239452, mapping within the PIM2 gene; OR, 1.17; 95% CI, 1.09-1.26; P = 9.93 × 10-8), the population-specific meta-analysis showed a genome-wide significant locus in East Asian individuals pointing to the same region (rs7059064, mapping within the GRIPAP1 gene; P = 6.2 × 10-9; OR, 1.33; 95% CI, 1.21-1.46). Indeed, rs7059064 tags a unique linkage disequilibrium block including 7 genes: TIMM17B, PQBP1, PIM2, SLC35A2, OTUD5, KCND1, and GRIPAP1, as well as a superenhancer (GH0XJ048933 within OTUD5) targeting all these genes. GH0XJ048933 is also predicted to target FOXP3, the main T-regulatory cell lineage specification factor. Consistently, OTUD5 and FOXP3 RNA levels were up-regulated in PBC case patients (1.75- and 1.64-fold, respectively). Conclusions: This work represents the first comprehensive study, to our knowledge, of the chrX contribution to the genetics of an autoimmune liver disease and shows a novel PBC-related genome-wide significant locus.

Introduction Public health care acknowledges socioeconomic factors as one of the multiple facets to promote or protect individual or collective health. Understanding and being more acquainted with the dynamics carried out in riverside communities is fundamental to investing in policies aimed at fighting diseases and illnesses that are particular to those communities. Objective Describing socioeconomic characteristics, healthcare infrastructure, and occupational activities of population from riverside communities along Tapajós river, Brazil. Methodology A descriptive study with 96 residents of communities of Tapajós river, Brazil. Participants have answered a semi-structure questionnaire and the analyses were descriptive and the variable categories were expressed as frequencies. Results There was a predominance of male participants (77.09%), incomplete elementary school (58.51%), involved in agricultural sector (85.10%), with a family income up to 1 minimum wage (68.81%). However, only 21.50% have declared making their living exclusively out of agriculture. Seedlings and seeds are mainly obtained through an exchange system running inside the community. In relation to infrastructure, the water comes from artesian wells (68.88%) and 51.63% claim not treating water whatsoever. All interviewees mentioned the lack of a sewage system and residues are taken to a rudimentary cesspool (76.59%). Waste produced by the community is burned out (93.61%). The main difficulties pointed out by the interviewees were: transportation (44.94%), health (32.14%), communication (21.42%) and government cooperation (15.47%). Conclusions The communities in this project show similar structural dynamic based on subsistence family agriculture and poor infrastructure of basic services. The data collected can be the basis for future public policies aiming at the promotion of food production autonomy, economic autonomy, and improvement of health indicators of these communities. Key messages Contextualizing the structural dynamic of vulnerable populations is key to plan actions aimed at tackling and dealing with social determinants involved in the health-illness process. Contextualizing the structural dynamic of vulnerable populations is fundamental to guide strategies aimed at intervening in the social and health determinants.

The cation binding ability of pectin was explored for the preparation of a highly active CaO catalyst for soybean oil transesterification. The catalyst was prepared by the precipitation method using Na2CO3 and Ca(NO3)2 in the presence of pectin followed by calcination. The best catalyst, CaP-600, was prepared at 600 °C and was characterized by FTIR, TGA, BET, CO2-TPD and powder X-ray diffraction (PXRD). CaP-600 was characterized as CaO containing carbonaceous materials left from pectin combustion. At only 1 wt% CaP-600 loading, biodiesel conversion reaches 99% after 4 h with a methanol:oil = 7:1 M ratio. Importantly, the calcium content in the produced biodiesel was only 0.7 ppm, which implies a satisfactory compliance with the ASTM D6751 and EN 14,214 standards. To the best of our knowledge, this is the best CaO catalyst reported for biodiesel production in terms of efficiency and amount of calcium leached. For comparison, CaO prepared in the absence of pectin showed poor catalytic activity in the optimized reaction conditions, demonstrating that the presence of the biopolymer prior to the calcination step is crucial for the catalytic performance of the CaO particles. Possible rationales for the biopolymer role are discussed.

Work-related psychosocial factors have been associated with metabolic syndrome. However, no systematic reviews or meta-analyses have evaluated this association.A systematic literature search was conducted, using PubMed, Embase, PsycINFO, PsycARTICLES and the Japan Medical Abstracts Society. Eligible studies included those that examined the previously mentioned association; had a longitudinal or prospective cohort design; were conducted among workers; provided sufficient data for calculating odds ratios, relative risks or hazard ratios with 95% confidence intervals; were original articles in English or Japanese; and were published no later than 2016. Study characteristics, exposure and outcome variables and association measures of studies were extracted by the investigators independently.Among 4,664 identified studies, 8 were eligible for review and meta-analysis. The pooled risk of adverse work-related stress on metabolic syndrome onset was significant and positive (RR = 1.47; 95% CI, 1.22-1.78). Sensitivity analyses limiting only the effects of job strain and shift work also indicated a significant positive relationship (RR = 1.75; 95% CI, 1.09-2.79; and RR = 1.59; 95% CI, 1.00-2.54, P = 0.049 respectively).This study reveals a strong positive association between work-related psychosocial factors and an elevated risk of metabolic syndrome onset. The effects of job strain and shift work on metabolic syndrome appear to be significant.

This paper proposes using of a Savitzky-Golay digital differentiator (SGDD) in difference operation method (DOM) algorithm to detect QRS complex in an electrocardiographic monitoring system. Such modification enables using the SGDD low-pass feature to eliminate hardware filtering stages. Moreover, the SGDD also eliminates 60-Hz noise by choosing the proper window size and polynomial order. A Savitzky-Golay digital differentiator with thirteen samples window and third order polynomial, running at 360-Hz, increases the signal-to-noise ratio in 25 times. Performance has been evaluated by comparing the figures of merit for false positives, false negatives and true positives between both original DOM algorithm and the proposed modified one, showing notorious improvements.

Supplementary_Material_revised for Evaluation of genotoxicity and subchronic toxicity of standardized rose hip extract by A Nagatomo, M Oguri, N Nishida, M Ogawa, A Ichikawa, and Y Tanaka-Azuma in Human & Experimental Toxicology

A three years old ox was referred to the University of Zambia Veterinary Clinic with a large protruded mass in the mouth. The slow growing oral mass was noticed three months earlier and contained displaced, loosely embedded incisor teeth. On clinical examination the mass was firm, large, round and located anterio-dorsally in the mandible. Histo-pathologically, tumor mass composed of neoplastic osteoblasts exhibiting osteoid and immature trabecular bony production. Neoplastic cells were positive for osterix marker expression. Gross pathology, radiology, cytology, immunohistochemistry and histopathology confirmed the mass as a mandibular osteosarcoma. This is a first and rare case of mandibular osteosarcoma being reported in cattle from Zambia and should be included in differential diagnosis of oral mass in cattle.

This paper proposes a novel robust optimization approach by combination of sensitivity analysis and sigma level estimation in multi-objective problems. In order to obtain robust Pareto-optima within acceptable computational costs, we actively reuse the already calculated data for the sensitivity analysis in multipoint search algorithm. The sigma level estimation is also utilized to select the significant solutions from a large number of Pareto-optima based on both the robustness and the performance. Some numerical results that verify the effectiveness of the proposed methods are presented.

We have proposed a novel thermally assisted magnetic recording head for future hard disk drives using a “Focusing Waveguide” (waveguide-type spot size converter). The Focusing Waveguide, which has a small size enough to be integrated into a flying slider, can focus the spot diameter of incident light less than one tenth while the light propagate only 200 μm in the waveguide. The focused spot illuminates a plasmon antenna to generate an enhanced near-field spot for heating a very small region of a recording media. We fabricated the Focusing Waveguide and evaluated its focusing properties by means of SNOM measurement method. A measured spot size was 0.37 μm × 0.42 μm (FWHM, Incident spot size = 5 μm). Since a core of the Focusing Waveguide is made of silicon, wavelength of the incident light was set to be 1310 nm. In order to examine the plasmon enhancement of the gold plasmon antenna at this wavelength, FDTD simulations and SNOM measurement was conducted. The results have shown that the combination of a gold plasmon antenna and the silicon substrate gives the fairly good plasmon enhancement at the wavelength of 1310 nm.

In recent years, power electronics utilization in modern devices has experienced a large growth due to several applications. For this reason, undergraduate laboratory courses in this field should have modern equipment for measurement and analysis of electrical signals. With this, students will have the opportunity to understand theoretical concepts in practice. However, commercial equipment of this nature have high finance costs. This is an obstacle for undergraduate courses with financial restrictions. This paper presents the development and testing of a low-cost platform for electrical measurement and frequency spectrum analysis, conceived to improve power electronics education. Experimental results done with different types of loads, such as power electronics converters, demonstrated acceptable measurements when compared with commercial equipment.

X-linked lymphoproliferative syndrome type 2 is a rare hereditary immunodeficiency caused by mutations in the XIAP gene. This immunodeficiency frequently results in hemophagocytic lymphohistiocytosis, although hypogammaglobulinemia and dysgammaglobulinemia are also common.We identified 17 patients from 12 Japanese families with mutations in XIAP. The Glu349del mutation was observed in 3 patients, each from a different family. Interestingly, these patients exhibited dysgammaglobulinemia but not hemophagocytic lymphohistiocytosis. We conducted an immunological study of patients carrying Glu349del and other mutations to elucidate the pathogenic mechanisms of dysgammaglobulinemia in patients with mutations in the XIAP gene.We performed an immunological study of 2 patients carrying the Glu349del mutation and 8 patients with other mutations.Flow cytometry showed that the percentage of memory B cells in patients with a mutation in XIAP was lower than that observed in the healthy controls. The patients with the Glu349del mutation had a lower percentage of memory B cells than those with other mutations. Ig production was reduced in patients with the Glu349del mutation. Increased susceptibility to apoptosis was observed in the patients with other mutations. Susceptibility to apoptosis was normal in patients with Glu349del. Microarray analysis indicated that expression of Ig-related genes was reduced in patients with the Glu349del mutation and that the pattern was different from that observed in the healthy controls or patients with other mutations in XIAP.Patients carrying the Glu349del mutation in the XIAP gene may have a clinically and immunologically distinct phenotype from patients with other XIAP mutations. The Glu349del mutation may be associated with dysgammaglobulinemia.

Significant associations of HLA-DP alleles with chronic hepatitis B (CHB) infection are evident in Asian and Arabian populations, including Japanese, Han Chinese, Korean, and Saudi Arabian populations. Here, significant associations between CHB infection and five DPB1 alleles (two susceptibility alleles, DPB1(*) 05:01 and (*) 09:01, and three protective alleles, DPB1(*) 02:01, (*) 04:01, and (*) 04:02) were confirmed in a population comprising of 2582 Japanese individuals. Furthermore, odds ratios for CHB were higher for those with both DPB1 susceptibility alleles than for those with only one susceptibility allele; therefore, effects of susceptibility alleles were additive for risk of CHB infection. Similarly, protective alleles showed an additive effect on protection from CHB infection. Moreover, heterozygotes of any protective allele showed stronger association with CHB than did homozygotes, suggesting that heterozygotes may bind a greater variety of hepatitis B-derived peptides, and thus present these peptides more efficiently to T-cell receptors than homozygotes. Notably, compound heterozygote of the protective allele (any one of DPB1*02:01, *04:01, and *04:02) and the susceptible allele DPB1*05:01 was significantly associated with protection against CHB infection, which indicates that one protective HLA-DPB1 molecule can provide dominant protection. Identification of the HLA-DPB1 genotypes associated with susceptibility to and protection from CHB infection is essential for future analysis of the mechanisms responsible for immune recognition of hepatitis B virus antigens by HLA-DPB1 molecules.

This study investigated whether an intestinal epithelial culture method can be applied to mouse and human esophageal cultures. The esophagi harvested from 1-day-old mice and adult humans were maintained in collagen gels. A commercially available culture medium for human embryonic stem cells was used for the human esophageal culture. We discovered that the intestinal epithelial culture method can be successfully applied to both mouse and human esophageal cultures. The long-term cultured esophageal organoids were rod-like luminal structures lined with myofibroblasts. We discovered that regeneration of the esophageal mucosal surface can be almost completely achieved in vitro, and the advantage of this method is that organoid cultures may be generated using host-derived fibroblasts as a niche. This method is a promising tool for mouse and human research in intestinal biology, carcinogenesis, and regenerative medicine.

Twisted nematic liquid crystal displays (TN-LCDs), doped with the nanoparticles of metal, such as Pd, Ag, or Ag-Pd, which are protected with ligand molecules, such as nematic liquid crystal, exhibit a frequency modulation (FM) electro-optical (EO) response with short response time of milliseconds (ms) or sub-ms order together with the ordinary rms voltage response. These devices are called FM/AM-TN-LCDs; they are distinct from the ordinary LCDs featured by the amplitude modulation (AM) response. The phenomena of the FM/AM LCDs may be attributed to the dielectric dispersion of a heterogeneous dielectric medium known as the Maxwell-Wagner effect. It is experimentally shown that the frequency range spreads from several tens hertz to several tens kilohertz and the spectrum is more or less centered about the dielectric relaxation frequency. We formulated a theory based on an equivalent circuit model to evaluate the dielectric relaxation frequency and the dielectric strengths; and we succeeded in explaining the dependence of the dielectric relaxation frequency on the concentration of nanoparticles and the their dielectric and electrical properties, whereas conventional theories based on electromagnetic theory are unable to explain this concentration dependence. This paper reports on the experimental results of the EO effects and the dielectric spectroscopy including the dielectric relaxation times and the dielectric strengths of nematic liquid crystal, 5CB (4-pentyl-4'-cyanobiphenyl), doped with the metal nanoparticles of I'd alone and Ag-Pd composite; and discusses how the observed dielectric relaxation frequency or dielectric relaxation time depend on the concentration of the doped nanoparticles and also their electrical and dielectric properties

In the present study, to evaluate the effect of pore size on bone ingrowth, we fabricated lotus stem-type titanium implants each with 4 square holes (diagonal length: 500, 600, 900 and 1200 μm) by using the rapid prototyping process with selective laser melting. These were then subjected to chemical and heat treatments to induce bioactivity. There were significant differences between bone ingrowth on the bioactive-treated and untreated implants. There were no significant differences for bone ingrowth among all holes in both implants. However, in both implants, the 1200-μm was found to be the best for bone invasion in the early stages of growth. On the other hand, both 500and 600-μm were found to be suitable for bone ingrowth from 6 weeks to 26 weeks in treated implants. Thus, the simple architecture of the implants allowed effective investigation of the influence of the interconnective pore size on osteconduction.

Porous titanium (Ti) metal with a structure similar to that of human cancellous bone was fabricated by selective laser melting (SLM) process. SEM observation showed that the core part of the walls of the porous body was completely melted by the laser beam and weakly bonded with small Ti particles on its surface. These Ti particles were joined with the core part by heating above 1000 °C, with remaining micro cavities on their surfaces. Tensile strength of the as-prepared solid rod was 530MPa and gradually decreased with increasing temperatures to 400MPa at 1300 °C, whereas its ductility increased with increasing temperatures. NaOH treatment formed fine network structure of sodium hydrogen titanate (SHT) on the walls of the porous Ti metal. The SHT was transformed into hydrogen titanates by HCl treatment and finally anatase and rutile by the heat treatment. Thus treated porous Ti metal formed apatite on its surface in simulated body fluid (SBF) within 3 days.

High frequency, medium power gyrotrons (Gyrotron FU series) have been developed at Fukui University as radiation sources covering a broad band from millimeter to submillimeter wave region. They have already been applied to high frequency electron spin resonance and to submillimeter wave scattering in plasma. Many parameters of the gyrotron series could be useful for applications in several new areas. The development and some applications of the Gyrotron FU series are summarized in this paper.

Frequency modulation of the gyrotron output has been numerically simulated employing the approximation of weakly relativistic, mono-velocity electron beam as well as a quasi-empirical approach. The simulation results are compared to a first experiment in the 300 GHz region performed with a submillimeter-wave gyrotron named "Gyrotron FU IV". The modulation amplitude of 30 MHz has been achieved by a 120 V modulation of the accelerating voltage resulting in the variation of the relativistic electron mass and in the corresponding modulation of the electron cyclotron frequency. Calculated amplitudes of frequency modulation are in reasonable agreement with the experimental results.

The cavity of the newest gyrotron, Gyrotron FU IVA in the high frequency series of Fukui University gyrotrons (the Gyrotron FU series) is designed to minimize the mode conversion from the main cavity mode to the higher modes. In this paper, the experimental results are compared with simulations for the complete gyrotron oscillator. The gyrotron has an additional advantage to cover the wide frequency range in submillimeter wave region.

Boron nitride films were prepared at 1 atm by r.f. thermal plasma chemical vapour deposition from the gas systems of Ar-BF3-N2 (or NH3, NF3)-H2, Ar-BCl3-N2 (or NH3, NF3)-H2, and Ar-B2H6-N2 (or NH3)-H2. The appearance and the deposition rate of the films changed drastically with the composition of the feed gas. Only from the Ar-BF3-N2(-NF3) gas, were transparent and smooth films obtained, while from other gas systems, white flaky or powder-like deposits formed. The structure of these films was basically sp2-bonded turbostratic BN, and the formation of cubic BN was not confirmed.

Recently, single nucleotide polymorphisms (SNPs) have been used to identify genes or genomic regions responsible for economic traits, including genetic diseases in domestic animals, and to examine genetic diversity of populations. In this study, we genotyped 70 chicken autosomal SNPs using DigiTag2 assay to understand the genetic structure of the Japanese native chicken breeds Satsumadori and Ingie, and the relationship of these breeds with other established breeds, Rhode Island Red (RIR), commercial broiler and layer. Five breeds, each consisting of approximately 20 chickens, were subjected to the assay, revealing the following: Average expected heterozygosities of broiler, Satsumadori, RIR, layer and Ingie were 0.265, 0.254, 0.244, 0.179 and 0.176, respectively. Phylogenetic analysis using the concatenated 70 autosomal SNP genotypes distinguished all chickens and formed clusters of chickens belonging to the respective breeds. In addition, the 2-D scatter plot of the first two principal components was consistent with the phylogenic tree. Taken together with the pairwise F(st) distances, broiler and RIR were closely positioned near each other, while Ingie was positioned far from the other breeds. Structure analysis revealed that the probable number of genetic clusters (K) was six and four with maximum likelihood and ΔK values, respectively. The clustering with maximum likelihood revealed that, in addition to the clustering of the other five breeds, the Satsumadori was subdivided into two genetic clusters. The clustering with ΔK value indicated that the broiler and Rhode Island Red were assigned to the same genetic cluster.

A method for multiresidue analysis of 48 pesticides (20 organophosphorus pesticides, 7 organochlorine pesticides, 14 organonitrogen pesticides, and 7 pyrethroid pesticides) permitted in Japan was systematically developed on the basis of capillary GC. Pesticides were simultaneously extracted with acetone from vegetable and fruit samples or with acetonitrile from lipid-containing crops and then re-extracted into ethyl acetate (test solution). Pesticides in the test solution were determined by capillary GC: Organophosphorus pesticides were directly determined by FPD-GC. Organonitrogen pesticides were determined by FTD-GC (NPD-GC) following cleanup by silica gel chromatography

Fifty-five patients with microcephaly (head circumference < -2SD) were identified. The 55 patients were divided into two groups, consisting of group 1 (34 cases) in which genetic causes were considered primary, and group 2 (21 cases) in which intrauterine and/or postnatal acquired factors were thought to be responsible. MRI abnormalities were present in 80% of the total series: 68 and 100% in groups 1 and 2, respectively. In group 1, migration abnormalities were the most prominent and mental retardation was the major neurological handicap, while in group 2, hydranencephaly and infarction secondary to brain circulatory derangements were the most frequently observed abnormalities, with severe multiple handicaps such as cerebral palsy, epilepsy and mental retardation seen. Head MRI was considered indispensable in the investigation of the causes of microcephaly and in determining the neurological prognosis of affected patients.

Many studies have shown that certain biomaterials with specific porous structures can induce bone formation in non-osseous sites without the need for osteoinductive biomolecules, however, the mechanisms responsible for this phenomenon (intrinsic osteoinduction of biomaterials) remain unclear. In particular, to our knowledge the type of pore structure suitable for osteoinduction has not been reported in detail. In the present study we investigated the effects of interconnective pore size on osteoinductivity and the bone formation processes during osteoinduction. Selective laser melting was employed to fabricate porous Ti implants (diameter 3.3mm, length 15 mm) with a channel structure comprising four longitudinal square channels, representing pores, of different diagonal widths, 500, 600, 900, and 1200 μm (termed p500, p600, p900, and p1200, respectively). These were then subjected to chemical and heat treatments to induce bioactivity. Significant osteoinduction was observed in p500 and p600, with the highest observed osteoinduction occurring at 5mm from the end of the implants. A distance of 5mm probably provides a favorable balance between blood circulation and fluid movement. Thus, the simple architecture of the implants allowed effective investigation of the influence of the interconnective pore size on osteoinduction, as well as the relationship between bone quantity and its location for different pore sizes.

This paper firstly presents fundamental modelling procedures which will be employed in production planning in process industries. Secondly, various optimization problems are discussed, which arise in the hierarchical levels of production planning. Then possible operations research methods to solve them are presented. Lastly, since there exist many combinatorial optimization problems in production planning activities, practical considerations of integer programming methods are discussed. Negative aspects of practical application of integer programming are also described.

The local effect of an interstitial hydrogenlike particle on localized f electrons was studied in PrPb3 by means of micro+ spin rotation and relaxation. Spontaneous micro+ spin precession with harmonic frequencies was observed for the first time in f electron compounds. We demonstrate that the signal is derived from a coupling between the micro+ spin and the hyperfine-enhanced nuclear spin of nearest neighbor (NN) 141Pr with Ising-like anisotropy. The signal also suggests a marked suppression of spin dynamics of the NN 141Pr in comparison with that of the bulk 141Pr. These facts strongly indicate modification of the f electronic state due to the interstitial charged particle.

The effect of the administration for 7 or 28 days of 50 mg/kg/day valproate (VPA) on carnitine metabolism and morphological changes of liver mitochondria in immature rats was evaluated. The dose of VPA was almost the same as that we clinically used. Carnitine concentrations in serum, red blood cells (RBC), muscle, liver and urine were measured. The rats treated with VPA for 7 days showed no significant change in carnitine concentration in each tissue examined or by morphology. In the serum, RBC and muscle of rats treated with VPA for 28 days, free carnitine levels decreased, while acylcarnitine levels and the ratio of acylcarnitine to free carnitine (acyl/free ratio) increased. Mitochondrial enlargement was also induced and urinary acyl/free ratio of VPA treated rats was higher than that of control rats after the 14th day of the treatment. These results suggest that carnitine deficiency and morphometric changes in mitochondria occur time dependent even if the dose of VPA is clinically appropriate.

A simulation code for an electron‐beam‐excited XeF(B→X) laser using Ar/Xe/F2 gas mixtures is described. The validity of the code was checked by comparing the computed results to those obtained in a previously reported experiment with a 65‐ns, 1.14‐MW/cm3 excitation pulse. Good agreement is demonstrated for sidelight fluorescence, laser waveforms, output power, and energy. Furthermore, the simulation code analysis suggests that the XeF laser can be operated effectively with low‐pressure (

This paper proposes the variables screening technique based on the stepwise multiple regression in multi-objective design optimization. This approach enables us to efficiently select the design variables that have a sufficient effect on machine performance. Some numerical results that demonstrate the validity of the proposed method are also presented

A new technique for distinguishing partial erasure from nonlinear transition shift (NLTS) is presented for the case of a dibit. Experimental results obtained by using the method show that the partial erasure of a square wave is twice as large as that of a dibit. Calculation of NLTS using a first-order approximation is not correct at high recording densities.

Background: Little information is available on the kinematics of the normal knee in deep flexion. The purpose of this study was to use magnetic resonance imaging to analyze the patellofemoral articulation in deep flexion. Methods: Axial scans were made of the patellofemoral joint of twenty healthy Japanese volunteers with the knee in approximately 90° of flexion, in maximum active flexion (mean [and standard deviation], 140° ± 10°), and in maximum passive flexion (mean, 156° ± 5°). A fat-suppressed, three-dimensional, fast low-angle shot sequence was used to visualize the articular cartilage. The patellofemoral contact area was determined on sequential images and was reconstructed three-dimensionally. Results: At 90° of flexion, the contact area on the patella was continuous over the medial and lateral facets in fourteen knees and was located in the proximal half of the articular surface. At maximum active and passive flexion, the odd facet engaged in fifteen and eighteen knees, respectively. At maximum passive flexion, the contact area of the lateral facet moved distally and decreased significantly (p = 0.0002). From 90° of flexion to maximum active flexion, the mean total contact area remained constant (3.43 ± 0.70 and 3.62 ± 0.72 cm 2, respectively); it then decreased significantly in maximum passive flexion (2.96 ± 0.78 cm 2, p = 0.04). Conclusions: The contact area on the patella was divided into two parts (the odd and lateral facets) and moved distally in deep knee flexion. The size of the contact area on the lateral facet significantly decreased in maximum passive flexion. Clinical Relevance: This study provides information that may be useful for the design of a knee prosthesis that permits a greater range of motion. Design modifications that include a smoother shape of the distal intercondylar notch to increase the contact area may be beneficial.

Recently, many studies have identified losses and gains of several chromosomal loci in human hepatocellular carcinoma (HCC) with fine microsatellite analysis and comparative genomic hybridization. Although distribution of aberrant chromosomal arms differs among HCCs, loss of 1p, 4q, 6q, 8p, 9p, 10q, 13q, 16q and 17p, and gain of 1q, 6p, 8q, 17q and 20q have been recurrently reported, and loss of 4q and 16q seems to occur preferentially in hepatitis B virus-related HCCs. Accumulation of these aberrant chromosomal regions is associated with tumor progression, and some chromosomal aberrations, such as loss of 1p, are frequently identified in well-differentiated HCCs and also detected even in dysplastic nodule and cirrhotic nodule. This evidence suggests that chromosomal instability (CIN) emerges at an early stage during hepatocarcinogenesis and is successively inherent to tumor cells, resulting in acquisition of malignant phenotype. The molecular basis of CIN is beginning to be explored; however, several mechanisms may be involved for CIN of HCC.

We performed photoreflectance (PR) and Raman-scattering measurements of long-range ordered Ga/sub 0.5/In/sub 0.5/P/GaAs heterointerfaces to investigate effects of the internal electric field on the carrier-modulation mechanism. The PR spectrum of an ordered Ga/sub 0.5/In/sub 0.5/P/GaAs heterointerface shows the Franz-Keldysh oscillation due to a strong internal electric field. However, the PR-signal amplitude for the ordered sample is /spl sim/1/20 of that for a disordered sample. Raman-scattering results of the ordered Ga/sub 0.5/In/sub 0.5/P/GaAs heterointerfaces reveal plasmon-phonon coupled modes due to the spontaneous electron accumulation. We suggest that the electron accumulation reduces the mean electric field for the PR modulation.

We evaluated the clinical usefulness of virtual CT gastroendoscopy (VCTGE).The subjects were 124 patients with endoscopically identified gastric lesions. VCTGE images were obtained using a GE-Navigator. We evaluated VCTGE in the visualization of gastric lesions for their presence and morphology.The detection rate of all gastric lesions by VCTGE was 76% (94 of 124 patients). The smallest detectable early gastric cancer was II c measuring 10 x 8 mm. The detection rates of each gastric lesion by VCTGE were 73% in early gastric cancer, and 90% in advanced gastric cancer. VCTGE imaging in the advanced gastric cancer was good in 12 (30%), fair in 25 (60%) and poor in 4 (10%). VCTGE imaging in early gastric cancer was good in 20 (46%), fair in 12 (27%) and poor in 12 (27%). The significance P level was 0.005 between the evaluation of the imaging of advanced and early gastric cancer.VCTGE visualized the characteristics of diverse gastric lesions and was considered useful for the detection and the diagnosis of these lesions.