シリコンマイグレーションシーリングによるウェーハレベル高真空パッケージングのための重要プロセス技術の開発

Tohoku University博士（工学）要約のみthesi

Selective hypermethylation is evident in small intestine samples from infants with necrotizing enterocolitis

OBJECTIVE: Necrotizing enterocolitis (NEC) is the most common and lethal gastrointestinal disease affecting preterm infants. NEC develops suddenly and is characterized by gut barrier destruction, an inflammatory response, intestinal necrosis and multi-system organ failure. There is currently no method for early NEC detection, and the pathogenesis of NEC remains unclear. DESIGN: To further understand the molecular mechanisms that support NEC, we used solution phase hybridization and next-generation DNA sequencing of bisulfite converted DNA to perform targeted genome-wide analysis of DNA methylation at high read depth. RESULTS: We found that ileal samples from surgical NEC infants (n = 5) exist in a broadly hypermethylated state relative to their non-NEC counterparts (n = 9). These trends were not uniform, with hypermethylation being most consistently observed outside CpG islands and promoters. We further identified several biologically interesting gene promoters that displayed differential methylation in NEC and a number of biological pathways that appear dysregulated in NEC. We also found that DNA methylation patterns identified in ileal NEC tissue were correlated with those found and published previously in stool samples from NEC-affected infants. CONCLUSION: We confirmed that surgical NEC is associated with broad DNA hypermethylation in the ileum, and this may be detectable in stool samples of affected individuals. Thus, an epigenomic liquid biopsy of stool may have significant potential as a biomarker with respect to the diagnostic/predictive detection of NEC. Our findings, along with recent similar observations in colon, suggest that epigenomic dysregulation is a significant feature of surgical NEC. These findings motivate future studies which will involve the longitudinal screening of samples obtained prior to the onset of NEC. Our long-term goal is the development of novel screening, diagnostic and phenotyping methods for NEC

Monitoring of the central blood pressure waveform via a conformal ultrasonic device.

Continuous monitoring of the central-blood-pressure waveform from deeply embedded vessels, such as the carotid artery and jugular vein, has clinical value for the prediction of all-cause cardiovascular mortality. However, existing non-invasive approaches, including photoplethysmography and tonometry, only enable access to the superficial peripheral vasculature. Although current ultrasonic technologies allow non-invasive deep-tissue observation, unstable coupling with the tissue surface resulting from the bulkiness and rigidity of conventional ultrasound probes introduces usability constraints. Here, we describe the design and operation of an ultrasonic device that is conformal to the skin and capable of capturing blood-pressure waveforms at deeply embedded arterial and venous sites. The wearable device is ultrathin (240 μm) and stretchable (with strains up to 60%), and enables the non-invasive, continuous and accurate monitoring of cardiovascular events from multiple body locations, which should facilitate its use in a variety of clinical environments

Global hypermethylation of intestinal epithelial cells is a hallmark feature of neonatal surgical necrotizing enterocolitis

BACKGROUND: Necrotizing enterocolitis (NEC) remains one of the overall leading causes of death in premature infants, and the pathogenesis is unpredictable and not well characterized. The aim of our study was to determine the molecular phenotype of NEC via transcriptomic and epithelial cell-specific epigenomic analysis, with a specific focus on DNA methylation. METHODS: Using laser capture microdissection, epithelial cell-specific methylation signatures were characterized by whole-genome bisulfite sequencing of ileal and colonic samples at the time of surgery for NEC and after NEC had healed at reanastomosis (n = 40). RNA sequencing was also performed to determine the transcriptomic profile of these samples, and a comparison was made to the methylome data. RESULTS: We found that surgical NEC has a considerable impact on the epigenome by broadly increasing DNA methylation levels, although these effects are less pronounced in genomic regions associated with the regulation of gene expression. Furthermore, NEC-related DNA methylation signatures were influenced by tissue of origin, with significant differences being noted between colon and ileum. We also identified numerous transcriptional changes in NEC and clear associations between gene expression and DNA methylation. CONCLUSIONS: We have defined the intestinal epigenomic and transcriptomic signatures during surgical NEC, which will advance our understanding of disease pathogenesis and may enable the development of novel precision medicine approaches for NEC prediction, diagnosis and phenotyping

Gab2 Ablation Reverses the Stemness of HER2-Overexpressing Breast Cancer Cells

Background/Aims: HER2 has been implicated in mammary tumorigenesis as well as aggressive tumor growth and metastasis. Its overexpression is related to a poor prognosis and chemoresistance in breast cancer patients. Although Grb2-associated binding protein 2 (Gab2) is important in the development and progression of human cancer, its effects and mechanisms in HER2-overexpressing breast cancer are unclear. Methods: Clone formation and MTT assays were used to examine cell proliferation. To detect the effect of Gab2 on the stemness of breast cancer cells, we used flow cytometry, a sphere formation assay, real-time PCR, and western blot. An animal model was created to validate the effect of Gab2 on tumor growth in vivo. Tissue slides were analyzed by immunohistochemistry. Results: Knockdown of Gab2 suppressed PI3K/AKT and MAPK/ERK pathway activity. Gab2 ablation also reduced the stemness of HER2-overexpressing breast cancer cells. In vivo, knockdown of Gab2 inhibited tumor growth. Conclusion: This study unveils a potential function of Gab2 in HER2-overexpressing breast cancer cells. Gab2 might be a potential target in the clinical therapy of HER2-overexpressing breast carcinoma

Development of Critical Process Technologies for Wafer-Level High Vacuum Packaging Based on Silicon Migration Sealing

要約の

Effects Of The Ground Plane Size On Radiation Pattern Of Reconfigurable Slot-Ring Antennas

In general, the radiation pattern of an antenna array can be predicted by the array factor and the radiation pattern of the array element. However, the radiation pattern of a reconfigurable slot-ring antenna varies with ground plane size. To explore the reconfigurable slot-ring antenna array performance, the effects of the ground plane size on radiation pattern of the reconfigurable slot-ring antenna is studied herein. Since the geometries of the reconfigurable slot-ring antenna working at different frequency bands are similar, a single slotring antenna with different ground plane sizes at 6.27 GHz is studied. The number of ripples in the radiation pattern increases as the size of the ground plane increases, which are due to the edge diffraction. Both a slot-ring antenna unit cell with periodic boundary conditions and a 5×5 slot-ring antenna array are simulated in HFSS. The radiation pattern of the unit cell multiplying with the array factor agrees very well with that of the 5×5 array. It can be concluded that the radiation pattern distortion caused by the edge diffraction will not exist in array applications

Integration Of Slot Antenna With Evanescent-Mode Filter For Tunable Front-End Applications

An evanescent-mode cavity filter integrated with a slot antenna is presented herein. Evanescent-mode cavities are commonly used to design low-loss filters due to their high quality (Q) factors and small size. The integration of the slot antenna and evanescent-mode filter provides nearly-zero transition loss with reduced size. The filter/antenna is designed at the center frequency of 8.56 GHz with a fractional bandwidth of 2.86%. The center frequency of this filter/antenna is then tuned from 8.18 to 8.80 GHz by just changing the resonant frequency of the resonators. The impedance matching, filtering shape, and radiation pattern of the filter/antenna system are preserved across the entire tuning range. © 2013 IEEE

Vertical Integration Of High-Q Filter With Circularly Polarized Patch Antenna With Enhanced Impedance-Axial Ratio Bandwidth

Directly coupling antennas to filters can remove the transition loss between the two and reduce the size of radio frequency front ends. Circularly polarized (CP) patch antennas with a single feed are very popular in many applications due to their compact size and ease of design. However, a probe-fed CP patch antenna typically exhibits only 1%-2% useful fractional bandwidth by considering both impedance matching and axial-ratio (AR) bandwidths. Thick substrates were used to realize single-feed CP antennas with wider bandwidth. However, thick substrates may cause issues, such as surface wave excitation, mutual coupling, and low efficiency. In this paper, we present a new approach to enhance the impedance-AR bandwidth of probe-fed CP patch antennas without using thick substrates. By integrating CP patch antennas with cavity filters and sequentially rotating the CP filter/patch antenna elements to form a 2 × 2 array, an impedance-AR bandwidth of 8.3% is achieved with the thickness of the antenna layer to be 0.0292λ 0. In addition, a third-order Chebyshev filtering function is embedded in this antenna array to enhance the out-of-band interference rejection

Single-Sided Radiation Of A Fractal-Shaped Reconfigurable Dual-Band Slot-Ring Antenna Using Electromagnetic Band-Gap Surfaces

This paper provides a ground plane solution for the fractal-shaped reconfigurable dual-band slot-ring antenna by using the Electromagnetic Band-Gap (EBG) surfaces. The EBG surface is designed with an in-phase bandwidth from 1.7 to 3.0 GHz. A distance between the EBG and the antenna is selected to be 7. 5 mm. The EBG-backed reconfigurable slot-ring antenna operates at two frequency bands based on the status of the switches loaded on the antenna. The lower band is observed from 2.0 to 3.7 GHz while higher band is from 4.9 to 8.4 GHz. During both frequency bands, the backside radiation of the antenna is reduced by the EBG surface