LTCC-Based DC-DC Converter for Reduction of Switching Noise and Radiated Emissions

In this study, a low-temperature co-fired ceramic (LTCC)-based direct current (DC)-DC converter is proposed for reducing stray inductance and mitigating electromagnetic interference. The dominant radiating loop of the proposed LTCC-based DC-DC converter features a multilayer design, which helps suppress noise sources and reduce radiated emissions. The peak voltage of switching noise for the proposed DC-DC converter at the frequency of 500 kHz is approximately 8.98% lower than that of a conventional DC-DC converter. In addition, the radiated emission level of the proposed DC-DC converter is lower than that of the conventional DC-DC converter. In sum, the proposed LTCC-technology-based multilayer design reduces the peak voltage of switching noise and the radiated emission of the DC-DC converter

Current Input Pixel-Level ADC with High SNR and Wide Dynamic Range for a Microbolometer

A readout circuit incorporating a pixel-level analog-to-digital converter (ADC) is studied for two-dimensional medium wavelength infrared microbolometer arrays. The signal-to-noise ratio (SNR) and charge handling capacity of the unit cell circuit are improved by using the current input pixel-level ADC. The charge handling capacity of the integrator is appropriately extended to maximize the integration time regardless of the magnitude of the input current and low power supply voltage. The readout circuit was fabricated using a 0.35-μm 2-poly 4-metal CMOS process for a 640 × 512 array with a pixel size of 40 μm × 40 μm. The peak SNR and dynamic range are 77.1 and 80.1 dB, respectively, with a power consumption of 0.62 μW per pixel

Nonuniformity-Immune Read-In Integrated Circuit for Infrared Sensor Testing Systems

In this study, a novel IR projector driver that can minimize nonuniformity in electric circuits, using a dual-current-programming structure, is proposed to generate high-quality infrared (IR) scenes for accurate sensor evaluation. Unlike the conventional current-mode structure, the proposed system reduces pixel-to-pixel nonuniformity by assigning two roles (data sampling and current driving) to a single transistor. A prototype of the proposed circuit was designed and fabricated using the SK-Hynix 0.18 µm CMOS process, and its performance was analyzed using post-layout simulation data. It was verified that nonuniformity, which is defined as the standard deviation divided by the mean radiance, could be reduced from 21% to less than 0.1%

Cross-talk between the TM4SF5/FAK and the IL6/STAT3 pathways renders immune escape of human liver cancer cells

TM4SF5 overexpressed in hepatocellular carcinoma activates FAK during tumor cell migration. However, it remains unknown how TM4SF5 in hepatocellular carcinoma cells compromise with immune actions initiated by extracellular cytokines. Normal and cancerous hepatocytes with or without TM4SF5 expression were analyzed for the effects of cytokine signaling activity on TM4SF5/FAK signaling and metastatic potential. We found that IL6 was differentially expressed in hepatocytes depending on cancerous malignancy and TM4SF5 expression. IL6 treatment activated FAK and STAT3 and enhanced focal adhesion (FA) formation in TM4SF5-null cells, but it decreased TM4SF6-dependent FAK activity and FAformation in SNU761-TM4SF5 cells. STAT3 suppression abolished the IL6-mediated effects in normal Chang cells, but it did not recover the TM4SF5-dependent FAK activity that was inhibited by IL6 treatment in cancerous SNU761-TM4SF5 cells. In addition, modulation of FAK activity did not change the IL6-mediated STAT3 activity in either the Chang or SNU761 cell system. TM4SF5 expression in SNU761 cells caused invasive extracellular matrix degradation negatively depending on IL6/IL6R signaling. Thus, it is likely that hepatic cancer cells might adopt TM4SF5-dependent FAK activation and metastatic potential by lowering IL6 expression and thus avoiding its immunological action through the IL6-STAT3pathway.OAIID:oai:osos.snu.ac.kr:snu2014-01/102/0000003910/7SEQ:7PERF_CD:SNU2014-01EVAL_ITEM_CD:102USER_ID:0000003910ADJUST_YN:NEMP_ID:A078142DEPT_CD:375CITE_RATE:5.372FILENAME:83jh-mcb.pdfDEPT_NM:약학과SCOPUS_YN:YCONFIRM:

N-terminus-independent activation of c-Src via binding to a tetraspan(in) TM4SF5 in hepatocellular carcinoma is abolished by the TM4SF5 C-terminal peptide application

Active c-Src non-receptor tyrosine kinase localizes to the plasma membrane via N-terminal lipid modification. Membranous c-Src causes cancer initiation and progression. Even though transmembrane 4 L six family member 5 (TM4SF5), a tetraspan(in), can be involved in this mechanism, the molecular and structural influence of TM4SF5 on c-Src remains unknown. Methods: Here, we investigated molecular and structural details by which TM4SF5 regulated c-Src devoid of its N-terminus and how cell-penetrating peptides were able to interrupt c-Src activation via interference of c-Src-TM4SF5 interaction in hepatocellular carcinoma models. Results: The TM4SF5 C-terminus efficiently bound the c-Src SH1 kinase domain, efficiently to the inactively-closed form. The complex involved protein tyrosine phosphatase 1B able to dephosphorylate Tyr530. The c-Src SH1 domain alone, even in a closed form, bound TM4SF5 to cause c-Src Tyr419 and FAK Y861 phosphorylation. Homology modeling and molecular dynamics simulation studies predicted the directly interfacing residues, which were further validated by mutational studies. Cell penetration of TM4SF5 C-terminal peptides blocked the interaction of TM4SF5 with c-Src and prevented c-Src-dependent tumor initiation and progression in vivo. Conclusions: Collectively, these data demonstrate that binding of the TM4SF5 C-terminus to the kinase domain of inactive c-Src leads to its activation. Because this binding can be abolished by cell-penetrating peptides containing the TM4SF5 C-terminus, targeting this direct interaction may be an effective strategy for developing therapeutics that block the development and progression of hepatocellular carcinoma.Y

Snail1 induced in breast cancer cells in 3D collagen I gel environment suppresses cortactin and impairs effective invadopodia formation

AbstractAlthough an in vitro 3D environment cannot completely mimic the in vivo tumor site, embedding tumor cells in a 3D extracellular matrix (ECM) allows for the study of cancer cell behaviors and the screening of anti-metastatic reagents with a more in vivo-like context. Here we explored the behaviors of MDA-MB-231 breast cancer cells embedded in 3D collagen I. Diverse tumor environmental conditions (including cell density, extracellular acidity, or hypoxia as mimics for a continuous tumor growth) reduced JNKs, enhanced TGFβ1/Smad signaling activity, induced Snail1, and reduced cortactin expression. The reduced JNKs activity blocked efficient formation of invadopodia labeled with actin, cortactin, or MT1-MMP. JNKs inactivation activated Smad2 and Smad4, which were required for Snail1 expression. Snail1 then repressed cortactin expression, causing reduced invadopodia formation and prominent localization of MT1-MMP at perinuclear regions. MDA-MB-231 cells thus exhibited less efficient collagen I degradation and invasion in 3D collagen I upon JNKs inhibition. These observations support a signaling network among JNKs, Smads, Snail1, and cortactin to regulate the invasion of MDA-MB-231 cells embedded in 3D collagen I, which may be targeted during screening of anti-invasion reagents

Lysyl-tRNA synthetase–expressing colon spheroids induce M2 macrophage polarization to promote metastasis

Lysyl-tRNA synthetase (KRS) functions canonically in cytosolic translational processes. However, KRS is highly expressed in colon cancer, and localizes to distinct cellular compartments upon phosphorylations (i.e., the plasma membranes after T52 phosphorylation and the nucleus after S207 phosphorylation), leading to probably alternative noncanonical functions. It is unknown how other subcellular KRSs crosstalk with environmental cues during cancer progression. Here, we demonstrate that the KRS-dependent metastatic behavior of colon cancer spheroids within 3D gels requires communication between cellular molecules and extracellular soluble factors and neighboring cells. Membranous KRS and nuclear KRS were found to participate in invasive cell dissemination of colon cancer spheroids in 3D gels. Cancer spheroids secreted GAS6 via a KRS-dependent mechanism and caused the M2 polarization of macrophages, which activated the neighboring cells via secretion of FGF2/GROα/M-CSF to promote cancer dissemination under environmental remodeling via fibroblast-mediated laminin production. Analyses of tissues from clinical colon cancer patients and Krs-/+ animal models for cancer metastasis supported the roles of KRS, GAS6, and M2 macrophages in KRS-dependent positive feedback between tumors and environmental factors. Altogether, KRS in colon cancer cells remodels the microenvironment to promote metastasis, which can thus be therapeutically targeted at these bidirectional KRS-dependent communications of cancer spheroids with environmental cues

Correlations between Transmembrane 4 L6 Family Member 5 (TM4SF5), CD151, and CD63 in Liver Fibrotic Phenotypes and Hepatic Migration and Invasive Capacities

<div><p>Transmembrane 4 L6 family member 5 (TM4SF5) is overexpressed during CCl₄-mediated murine liver fibrosis and in human hepatocellular carcinomas. The tetraspanins form tetraspanin-enriched microdomains (TEMs) consisting of large membrane protein complexes on the cell surface. Thus, TM4SF5 may be involved in the signal coordination that controls liver malignancy. We investigated the relationship between TM4SF5-positive TEMs with liver fibrosis and tumorigenesis, using normal Chang hepatocytes that lack TM4SF5 expression and chronically TGFβ1-treated Chang cells that express TM4SF5. TM4SF5 expression is positively correlated with tumorigenic CD151 expression, but is negatively correlated with tumor-suppressive CD63 expression in mouse fibrotic and human hepatic carcinoma tissues, indicating cooperative roles of the tetraspanins in liver malignancies. Although CD151 did not control the expression of TM4SF5, TM4SF5 appeared to control the expression levels of CD151 and CD63. TM4SF5 interacted with CD151, and caused the internalization of CD63 from the cell surface into late lysosomal membranes, presumably leading to terminating the tumor-suppressive functions of CD63. TM4SF5 could overcome the tumorigenic effects of CD151, especially cell migration and extracellular matrix (ECM)-degradation. Taken together, TM4SF5 appears to play a role in liver malignancy by controlling the levels of tetraspanins on the cell surface, and could provide a promising therapeutic target for the treatment of liver malignancies.</p></div

The relationships of TM4SF5, CD151, and CD63 in the development of murine liver fibrosis and liver cancer.

<p>(A to D) Liver tissues from mice administrated with control vehicle or CCl₄ every other day for 2 weeks were used for RT-PCR analysis (A), harvested for whole extracts, prior to Western blots for the indicated proteins (B), used for Masson’s trichrome staining to determine collagen I expression (C), or processed for immunohistochemistry with double-staining for TM4SF5 and CD151 (D). (E) Human normal or liver tumor tissues were processed for Western blots or immunohistochemistry to identify CD151 (top), TM4SF5 (middle), and CD63 (bottom) and the nuclei were stained using DAPI. Scale bars depict 10 µm. Data represent three independent experiments.</p

Different collaborative effects of TM4SF5, CD151, and CD63 on migration and invasive ECM degradation.

<p>Transwell migration analyses (A to D) or ECM-degradation analyses (E to H) were performed using Chang-TGFβ1 cells transfected with the indicated shRNAs or plasmids. (A to D) The bottom chamber was filled with 10% FBS/DMEM-H. After 18 h, cells migrated to the bottom surface of the filter were stained and imaged. Representative images (at least 5 images) were counted to determine migration in each experimental condition. Mean ± standard deviation were graphed (A to C), and representative images of (C) were shown (D). (E to H) Chang-TGFβ1 cells transfected with shRNA or plasmids were reseeded onto coverslips precoated with Oregon Green 488-conjugated gelatin and incubated for 18 h in a CO₂ incubator. The dark-spotted ECM-degraded areas from more than 5 random images were counted for graphic presentations using mean ± standard deviation. Representative images in (H) are shown (G). * or ** depict <i>P</i> values less than 0.001 or 0.05 for statistical significance, respectively, whereas *** depicts <i>P</i> values greater than 0.05 for insignificance, and numbers in (B) represent the <i>P</i> values by Student’s <i>t</i>-tests. Data represent three independent experiments.</p