Addition of Synthetic Biomaterials to Deproteinized Bovine Bone Mineral (DBBM) for Bone Augmentation—A Preclinical In Vivo Study

(1) Aim: To investigate the effect of synthetic bone substitutes, α-tricalcium phosphate (α-TCP) or bi-layered biphasic calcium-phosphate (BBCP) combined with deproteinized bovine bone mineral (DBBM), on bone formation. (2) Methods: Thirty critical size defects were randomly treated with the following five different treatment modalities: (1) negative control (NC, empty), (2) DBBM, (3) α-TCP + DBBM (1:1), (4) BBCP 3%HA/97%α-TCP + DBBM (1:1), and (5) BBCP 6%HA/94%α-TCP + DBBM (1:1). The samples, at four weeks post-surgery, were investigated by micro-CT and histological analysis. (3) Results: A similar level of new bone formation was demonstrated in the DBBM with α-TCP bone substitute groups when compared to the negative control by histomorphometry. DBBM alone showed significantly lower new bone area than the negative control (p = 0.0252). In contrast to DBBM, the micro-CT analysis revealed resorption of the α-TCP + DBBM, BBCP 3%HA/97%α-TCP + DBBM and BBCP 6%HA/94%α-TCP + DBBM, as evidenced by a decrease of material density (p = 0.0083, p = 0.0050 and p = 0.0191, respectively), without changing their volume. (4) Conclusions: New bone formation was evident in all defects augmented with biomaterials, proving the osteoconductive properties of the tested material combinations. There was little impact of the HA coating degree on α-TCP in bone augmentation potential and material resorption for four weeks when mixed with DBBM.     

The Detection of Immunity against WT1 and SMAD4P130L of EpCAM+ Cancer Cells in Malignant Pleural Effusion

Malignant pleural effusion (MPE) provides a liquid tumor microenvironment model that includes cancer cells and immune cells. However, the characteristics of tumor antigen-specific CD8⁺ T cells have not been investigated in detail. Here, we analyzed MPE samples taken from a patient with pancreatic cancer who received a dendritic cell vaccine targeting Wilms’ Tumor 1 (WT1) antigen over the disease course (two points at MPE^1st and 2^nd, two months after MPE1^st). Epithelial cell adhesion molecule (EpCAM)⁺ cancer cells (PD-L1⁻ or T cell immunoglobulin mucin-3, TIM-3⁻), both PD-1 or TIM-3 positive CD8⁺ T cells, and CD14⁺CD68⁺CD163⁺TIM-3⁺ macrophages increased from the MPE^1st to MPE^2nd. The ratio of WT1-specific cytotoxic lymphocytes (WT1-CTLs) to MPE CD8⁺ T cells and IFN-γ secretion of WT1-CTLs were reduced with disease progression. Coincidentally, the fraction of central memory T (T_CM) of WT1-CTLs was decreased. On the other hand, CD8⁺ T cells in response to SMAD4^P130L, which is homogeneously expressed in EpCAM⁺ cancer cells, were detected using in vitro expansion with the HLA-A*11:01 restrictive SVCVNLYH neoantigen. Furthermore, the CD8⁺ T cell response to SMAD4^P130L was diminished following remarkably decreased numbers of CD8⁺ T_CM in MPE samples. In conclusion, CD8⁺ T cells responding to WT1 or SMAD4^P130L neoantigen expressed in EpCAM⁺ pancreatic cancer cells were detected in MPE. A tumor antigen-specific immune response would provide novel insight into the MPE microenvironment.     

Hydrogen incorporation in tungsten deposits growing by deuterium plasma sputtering

Tungsten deposits were produced by sputtering method using hydrogen isotope RF plasma, and the density and the incorporated components in the deposits were investigated. The density changed in the range from 14.2 g/cm³ to 6.1 g/cm³, and hydrogen isotope retention changed in the range from 0.25 to 0.05 as (H + D)/W by the difference of deposition conditions. Both the density and hydrogen isotope retention tended to decrease with an increase of pressure. Even though a deuterium gas was used for producing tungsten deposits, not only deuterium but also hydrogen, oxygen and water vapor were incorporated in the deposits. It is considered that the incorporation of these components originated in water vapor unintentionally existing in the vacuum chamber.     

Computation of mutual entropy in quantum markov chains

There are several damping phenomena in quantum optics. Such phenomena have been usually explained by open systems. In statistical physics, open system dynamics have been used to study the irreversibility and the approach to equilibrium. In this paper, the dynamical change of the mutual entropy for an open system, frequently studied in the quantum optics literature, is rigorously computed through a model of quantum Markov chain. In particular, the concrete formula of Stinespring expression for such a model is obtained and applied to the derivation of the mutual entropy, and some computational results are presented.     

Highly reliable copper dual-damascene interconnects with self-formed MnSi/sub x/O/sub y/ barrier Layer

Copper (Cu) dual-damascene interconnects with a self-formed MnSi/sub x/O/sub y/ barrier layer were successfully fabricated. Transmission electron microscopy shows that approximately 2-nm thick and continuous MnSi/sub x/O/sub y/ layer was formed at the interface of Cu and dielectric SiO/sub 2/, and that no barrier was formed at the via bottom because no oxygen was at the via bottom during annealing. No leakage-current increase was observed, and electron energy loss analysis shows that no Cu was in SiO/sub 2/, suggesting that MnSi/sub x/O/sub y/ layer has sufficient barrier properties for Cu, and that the concept of self-forming barrier process works in Cu dual-damascene interconnects. Via chain yield of more than 90% and 50% reduction in via resistance were obtained as compared with physical vapor deposited tantalum barrier, because there is no barrier at the via bottom. In addition, no failure in the stress-induced voiding measurement was found even after a 1600-h testing. No failure in electromigration (EM) testing was found, as the electron flow is from the lower level interconnects through via up to upper level interconnects even after 1000-h testing. At least, four times EM lifetime improvement was obtained in the case of electron flow from upper level interconnect through via down to lower level interconnects. Significant EM lifetime improvement is due to no flux divergence site at the via bottom, resulting from there being no bottom barrier at the via.     

Indoor and outdoor concentrations of Japanese cedar pollens and total suspended particulates: A case study at a kindergarten in Japan

Japanese cedar pollinosis (JCP) caused by allergenic cedar and cypress pollens is one of major economic and health issues in Japan. The present study reported here aimed to provide basic data to understand the status of early life exposures to airborne cedar and cypress pollens in school settings. In particular, the study investigated relationships between indoor and outdoor concentrations of airborne cedar and cypress pollens and total suspended particulates (TSP) in a kindergarten in Japan. Overall, outdoor concentrations of the airborne pollens and TSP were higher than the indoor concentrations, i.e., indoor to outdoor (I/O) ratios of 0.043–0.055 and 0.545 for the airborne pollens and TSP, respectively. The smaller I/O ratios for the pollens were expected because the larger pollen grains (20–30 μm in diameter) were less likely penetrated to indoor environment than for smaller airborne particulates. The present study also found increased TSP concentrations during the pollen season was likely attributed to increased airborne pollen concentrations. By understanding the status of indoor and outdoor concentrations of airborne cedar and cypress pollens in school settings, early life exposures to these allergenic pollens should be effectively minimized to prevent subsequent progression to JCP symptoms.     

An improved shift-invariant artificial neural network for computerized detection of clustered microcalcifications in digital mammograms

A shift-invariant artificial neutral network (SIANN) has been applied to eliminate the false-positive detections reported by a rule-based computer aided-diagnosis (CAD) scheme developed in our laboratory. Regions of interest (ROIs) were selected around the centers of the rule-based CAD detections and analyzed by the SIANN. In our previous study, background-trend correction and pixel-value normalization were used as the preprocessing of the ROIs prior to the SIANN. A ROI is classified as a positive ROI, if the total number of microcalcifications detected in the ROI is greater than a certain number. In this study, modifications were made to improve the performance of the SIANN. First, the preprocessing is removed because the result of the background-trend correction is affected by the size of ROIs. Second, image-feature analysis is employed to the output of the SIANN in an effort to eliminate some of the false detections by the SIANN. In order to train the SIANN to detect microcalcifications and also to extract image features of microcalcifications, the zero-mean-weight constraint and training-free-zone techniques have been developed. A cross-validation training method was also applied to avoid the overtraining problem. The performance of the SIANN was evaluated by means of ROC analysis using a database of 39 mammograms for training and 50 different mammograms for testing. The analysis yielded an average area under the ROC curve (A(z)) of 0.90 for the testing set. Approximately 62% of false-positive clusters detected by the rule-based scheme were eliminated without any loss of the true-positive clusters by using the improved SIANN with image feature analysis techniques.     

Evaluation of glomerular filtration rate by camera-based method in both children and adults

We describe a method to evaluate glomerular filtration rate (GFR) in both children and adults using 99mTc-diethylenetriamine pentaacetic acid (DTPA) and a gamma camera. METHODS: Renal scintigraphy with 99mTc-DTPA was performed in 40 children and 92 adults with various degrees of renal function. The percent renal uptake at 2-2.5 min after tracer arrival in the kidney was determined with background subtraction and correction for soft-tissue attenuation and was correlated by linear regression analysis with GFR measured from two blood samples. A perirenal region of interest was used for background subtraction. Renal depth was computed using the equations determined or validated on the basis of CT measurements, and the attenuation coefficient was set at 0.12. The obtained regression equation was used to predict GFR. Renal function was also assessed by the Gates' method. RESULTS: Percent renal uptake was closely correlated with GFR normalized for body surface area in all patients (y = 15.958x - 2.94; r = 0.939). GFR was successfully predicted using the regression equation in both children and adults. Gates' method severely overestimated GFR in children and provided less accurate values even in adults than our method. CONCLUSION: The method presented here requires neither blood sampling nor additional imaging and allows estimation of GFR in both children and adults.     

Device modeling and simulations toward sub-10 nm semiconductordevices

This paper overviews the fundamental problems encountered in device modeling and simulations of sub-10 nm Si metal-oxide-semiconductor field-effect-transistors (MOSFETs). We focus on the two fundamental problems: the quantum effects and the effects associated with the long-range Coulomb potential. It is pointed out that these problems are profoundly related to the basic principles of device physics and even pose a question on the validity of the basic transport equation which the present device simulations are based on. We also review various approaches and methods taken to tackle those problems