Silicon based complementary metal-oxide-semiconductor field-effect-transistor (CMOSFET) technology has continued to progress unabated for last five decades despite various challenges arising due to ...extreme scaling. Pervasive use of Si technology is evident in a large spectrum of products ranging from high end mainframe and server computers for businesses to laptops, smartphones, and internet of things (IoT) for consumer-oriented products. There is an ever-increasing demand to improve Si device performance for the above described and future products. Strain engineering is one of the key aspects to improve transistor performance. In this review, we describe strain engineering in silicon based advanced CMOS technology, which has evolved from conventional two-dimensional (2D) MOSFET structure to 3D FinFET structure. The impact of shrinking dimensions of scaled FinFETs on channel strain engineering as well as options for strain engineering in future CMOS architecture are described. Finally, strain engineering in non-silicon based functional materials such as gallium nitride (GaN) and 2D materials will be briefly discussed.
In this paper, for the first time we demonstrate that horizontally stacked gate-all-around (GAA) Nanosheet structure is a good candidate for the replacement of FinFET at the 5nm technology node and ...beyond. It offers increased W eff per active footprint and better performance compared to FinFET, and with a less complex patterning strategy, leveraging EUV lithography. Good electrostatics are reported at L g =12nm and aggressive 44/48nm CPP (Contacted Poly Pitch) ground rules. We demonstrate work function metal (WFM) replacement and multiple threshold voltages, compatible with aggressive sheet to sheet spacing for wide stacked sheets. Stiction of sheets in long-channel devices is eliminated. Dielectric isolation is shown on standard bulk substrate for sub-sheet leakage control. Wrap-around contact (WAC) is evaluated for extrinsic resistance reduction.
Intra-articular injection of hyaluronan (HA) has been suggested to have a disease-modifying effect in osteoarthritis, but little is known about the possible mechanisms.
To investigate the effects of ...HA species of different molecular mass, including 800 kDa (HA800) and 2700 kDa (HA2700), on the expression of aggrecanases (ie, ADAMTS species), which play a key role in aggrecan degradation.
The effects of HA species on the expression of ADAMTS1, 4, 5, 8, 9 and 15 in interleukin 1alpha (IL1alpha)-stimulated osteoarthritic chondrocytes were studied by reverse transcription PCR and real-time PCR. Expression of ADAMTS4 protein and aggrecanase activity and signal transduction pathways of IL1, CD44 and intracellular adhesion molecule 1 (ICAM1) were examined by immunoblotting.
IL1alpha treatment of chondrocytes induced ADAMTS4, and HA800 and HA2700 significantly decreased IL1alpha-induced expression of ADAMTS4 mRNA and protein. IL1alpha-stimulated aggrecanase activity in osteoarthritic chondrocytes was reduced by treatment with HA2700 or transfection of small interfering RNA for ADAMTS4. A similar result was obtained when HA2700 was added to explant cultures of osteoarthritic cartilage. HA2700 neither directly inhibited nor bound to ADAMTS4. Downregulation of ADAMTS4 expression by HA2700 was attenuated by treatment of IL1alpha-treated chondrocytes with antibodies to CD44 and/or ICAM1. The increased phosphorylation of IL1 receptor-associated kinase-1 and extracellular signal-regulated protein kinase1/2 induced by the IL1alpha treatment was downregulated by enhanced IRAK-M expression after HA2700 treatment.
These data suggest that HA2700 suppresses aggrecan degradation by downregulating IL1alpha-induced ADAMTS4 expression through the CD44 and ICAM1 signalling pathways in osteoarthritic chondrocytes.
Radionuclide therapy (RNT) is an internal radiation therapy that can selectively damage cancer cells. Recently, the use of alpha-emitting radionuclides was initiated in RNT owing to its dose ...concentration and short range. In particular, 223Ra is widely used for bone metastasis of prostate cancer. Despite its potential for clinical applications, it is difficult to determine whether a drug has been properly delivered to the target lesion. As such, we propose a new method of monitoring nuclear gamma rays promptly and simultaneously emitted from 223Ra as alpha decay using a high-sensitivity Compton camera. We first observed a small bottle of 223Ra solution with a total radioactivity of 0.56 MBq. The reconstructed image converged at the correct position with a position resolution of ∼20 mm at a plane 10 cm in front of the camera. Next, we observed a phantom consisting of three spheres with diameters ranging from 13 to 37 mm filled with 223Ra solution (9 kBq/mL) and then surrounded by a ∼20-cm layer of water. A three-dimensional (3D) image was constructed by rotating the Compton camera around the phantom. Images were then acquired from eight directions at 30-min intervals, respectively. Although the image resolution remained limited at 351 keV, three spheres were resolved at the correct position in the 3D image with their relative intensities. Thirdly, we observed the body of a patient for 10 min and reconstructed almost the same accumulation as the image acquired by a single-photon emission computed tomography (SPECT) system for 30 min. While the spatial resolution of the Compton camera was worse, DOI-CC obtained a wider image in a shorter time. Finally, we discuss current problems and plans for improving sensitivity and angular resolution for future clinical applications.
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Considerable amounts of radioactive substances (mainly 137Cs and 134Cs) were released into the environment after the Japanese nuclear disaster in 2011. Some restrictions on residence areas were ...lifted in April 2017, owing to the successive and effective decontamination operations. However, the distribution of radioactive substances in vast areas of mountain, forest and satoyama close to the city is still unknown; thus, decontamination operations in such areas are being hampered. In this paper, we report on the first aerial gamma-ray imaging of a schoolyard in Fukushima using a drone that carries a high sensitivity Compton camera. We show that the distribution of 137Cs in regions with a diameter of several tens to a hundred meters can be imaged with a typical resolution of 2–5 m within a 10–20 min flights duration. The aerial gamma-ray images taken 10 m and 20 m above the ground are qualitatively consistent with a dose map reconstructed from the ground-based measurements using a survey meter. Although further quantification is needed for the distance and air-absorption corrections to derive in situ dose map, such an aerial drone system can reduce measurement time by a factor of ten and is suitable for place where ground-based measurement are difficult.
Proton therapy is a widely used and effective treatment for cancer. A high-dose concentration of proton beam reduces damage to normal tissues. However, it also requires a high accuracy of ...irradiation. PET is generally used to verify the proton range after irradiation, but, the distributions of positrons and the energy deposited by protons are not similar to each other. Recently, prompt gamma-ray imaging has attracted attention as a new, online imaging technique. In particular, 4.4 MeV gamma rays emitted from 12C* is one of the best probes to monitor the proton dose, however imaging techniques are far from established. We have developed a novel, 3-D position sensitive Compton camera based on Ce:GAGG scintillators coupled with multi-pixel photon counter (MPPC) arrays, thus making it optimized for imaging in the 1–10 MeV range. The angular resolution is 5 degrees (FWHM) at 4.4 MeV. We have established various methods to discriminate multiple-Compton and escape events, both of which can be critical backgrounds for precise imaging of prompt gamma rays. By irradiating a 70 MeV proton beam on the PMMA phantom, we demonstrated that 4.4 MeV gamma ray image is sharply concentrated on the Bragg peak, as was expected from the PHITS simulation.
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A new triclinic crystal form of human serum albumin (HSA), derived either from pool plasma (pHSA) or from a Pichia pastoris expression system (rHSA), was obtained from polyethylene glycol 4000 ...solution. Three-dimensional structures of pHSA and rHSA were determined at 2.5 Å resolution from the new triclinic crystal form by molecular replacement, using atomic coordinates derived from a multiple isomorphous replacement work with a known tetragonal crystal form. The structures of pHSA and rHSA are virtually identical, with an r.m.s. deviation of 0.24 Å for all Cα atoms. The two HSA molecules involved in the asymmetric unit are related by a strict local twofold symmetry such that the Cα atoms of the two molecules can be superimposed with an r.m.s. deviation of 0.28 Å in pHSA. Cys34 is the only cysteine with a free sulfhydryl group which does not participate in a disulfide linkage with any external ligand. Domains II and III both have a pocket formed mostly of hydrophobic and positively charged residues and in which a very wide range of compounds may be accommodated. Three tentative binding sites for long-chain fatty acids, each with different surroundings, are located at the surface of each domain.
Particle therapy is an advanced cancer therapy that uses a feature known as the Bragg peak, in which particle beams suddenly lose their energy near the end of their range. The Bragg peak enables ...particle beams to damage tumors effectively. To achieve precise therapy, the demand for accurate and quantitative imaging of the beam irradiation region or dosage during therapy has increased. The most common method of particle range verification is imaging of annihilation gamma rays by positron emission tomography. Not only 511-keV gamma rays but also prompt gamma rays are generated during therapy; therefore, the Compton camera is expected to be used as an on-line monitor for particle therapy, as it can image these gamma rays in real time. Proton therapy, one of the most common particle therapies, uses a proton beam of approximately 200 MeV, which has a range of ∼ 25 cm in water. As gamma rays are emitted along the path of the proton beam, quantitative evaluation of the reconstructed images of diffuse sources becomes crucial, but it is far from being fully developed for Compton camera imaging at present. In this study, we first quantitatively evaluated reconstructed Compton camera images of uniformly distributed diffuse sources, and then confirmed that our Compton camera obtained 3 %(1σ) and 5 %(1σ) uniformity for line and plane sources, respectively. Based on this quantitative study, we demonstrated on-line gamma imaging during proton irradiation. Through these studies, we show that the Compton camera is suitable for future use as an on-line monitor for particle therapy.
The morphogenesis and remodeling of bone depends on the integrated activity of osteoblasts that form bone and osteoclasts that resorb bone. We previously reported the isolation of a new cytokine ...termed osteoclastogenesis inhibitory factor, OCIF, which specifically inhibits osteoclast development. Here we report the cloning of a complementary DNA of human OCIF. OCIF is identical to osteoprotegerin (OPG), a soluble member of the tumor-necrosis factor receptor family that inhibits osteoclastogenesis. Recombinant human OPG/OCIF specifically acts on bone tissues and increases bone mineral density and bone volume associated with a decrease of active osteoclast number in normal rats. Osteoblasts or bone marrow-derived stromal cells support osteoclastogenesis through cell-to-cell interactions. A single class of high affinity binding sites for OPG/OCIF appears on a mouse stromal cell line, ST2, in response to 1,25-dihydroxyvitamin D3. An anti-OPG/OCIF antibody that blocks the binding abolishes the biological activity of OPG/OCIF. When the sites are blocked with OPG/OCIF, ST2 cells fail to support osteoclastogenesis. These results suggest that the sites are involved in cell-to-cell signaling between stromal cells and osteoclast progenitors and that OPG/OCIF inhibits osteoclastogenesis by interrupting the signaling through the sites.
In proton therapy, the delivered dose should be monitored to a high degree of accuracy to avoid unnecessary exposure to healthy tissues and critical organs. Although positron emission tomography ...(PET) is most frequently used to verify the proton range, the nuclear reactions between protons and nuclei that generate positrons do not necessarily correspond to the actual proton range. Moreover, such imaging must be conducted after the treatment irradiation, because a PET gantry cannot be used in conjunction with a proton therapy beam. In this paper, we studied one-dimensional (1D) and two-dimensional (2D) distributions of prompt gamma rays of various energies, to determine the most suitable energy window for online monitoring in proton therapy. After an initial simulation study using the particle and heavy ion transport code system (PHITS), we irradiated a poly(methyl methacrylate) (PMMA) phantom with a 70-MeV proton beam to mimic proton range verification in a clinical situation. Using a newly developed Compton camera, we have experimentally confirmed for the first time that 4.4-MeV gamma rays emitted from 12C and 16O match the exact position of the Bragg peak in proton range verification.
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