Homozygous null mutation of tumor suppressor
gene leads to severe neural diseases, metabolic disorders and early death in the newborns of humans, mice and rats. WWOX is frequently downregulated in ...the hippocampi of patients with Alzheimer's disease (AD).
analysis revealed that knockdown of WWOX protein in neuroblastoma cells results in aggregation of TRAPPC6AΔ, TIAF1, amyloid β, and Tau in a sequential manner. Indeed, TRAPPC6AΔ and TIAF1, but not tau and amyloid β, aggregates are present in the brains of healthy mid-aged individuals. It is reasonable to assume that very slow activation of a protein aggregation cascade starts sequentially with TRAPPC6AΔ and TIAF1 aggregation at mid-ages, then caspase activation and APP de-phosphorylation and degradation, and final accumulation of amyloid β and Tau aggregates in the brains at greater than 70 years old. WWOX binds Tau-hyperphosphorylating enzymes (e.g., GSK-3β) and blocks their functions, thereby supporting neuronal survival and differentiation. As a neuronal protective hormone, 17β-estradiol (E2) binds WWOX at an NSYK motif in the
-terminal SDR (short-chain alcohol dehydrogenase/reductase) domain. In this review, we discuss how WWOX and E2 block protein aggregation during neurodegeneration, and how a 31-amino-acid zinc finger-like Zfra peptide restores memory loss in mice.
Synthetic Zfra4-10 and WWOX7-21 peptides strongly suppress cancer growth in vivo. Hypothetically, Zfra4-10 binds to the membrane Hyal-2 of spleen Z cells and activates the Hyal-2/WWOX/SMAD4 signaling ...for cytotoxic Z cell activation to kill cancer cells. Stimulation of membrane WWOX in the signaling complex by a WWOX epitope peptide, WWOX7-21, is likely to activate the signaling. Here, mice receiving Zfra4-10 or WWOX7-21 peptide alone exhibited an increased binding of endogenous tumor suppressor WWOX with ERK, C1qBP, NF-κB, Iba1, p21, CD133, JNK1, COX2, Oct4, and GFAP in the spleen, brain, and/or lung which led to cancer suppression. However, when in combination, Zfra4-10 and WWOX7-21 reduced the binding of WWOX with target proteins and allowed tumor growth in vivo. In addition to Zfra4-10 and WWOX7-21 peptides, stimulating the membrane Hyal-2/WWOX complex with Hyal-2 antibody and sonicated hyaluronan (HAson) induced Z cell activation for killing cancer cells in vivo and in vitro. Mechanistically, Zfra4-10 binds to membrane Hyal-2, induces dephosphorylation of WWOX at pY33 and pY61, and drives Z cell activation for the anticancer response. Thus, Zfra4-10 and WWOX7-21 peptides, HAson, and the Hyal-2 antibody are of therapeutic potential for cancer suppression.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Tumor suppressor WWOX inhibits cancer growth and retards Alzheimer’s disease (AD) progression. Supporting evidence shows that the more strongly WWOX binds intracellular protein partners, the weaker ...is cancer cell growth in vivo. Whether this correlates with retardation of AD progression is unknown. Two functional forms of WWOX exhibit opposite functions. pY33-WWOX is proapoptotic and anticancer, and is essential for maintaining normal physiology. In contrast, pS14-WWOX is accumulated in the lesions of cancers and AD brains, and suppression of WWOX phosphorylation at S14 by a short peptide Zfra abolishes cancer growth and retardation of AD progression. In parallel, synthetic Zfra4-10 or WWOX7-21 peptide strengthens the binding of endogenous WWOX with intracellular protein partners leading to cancer suppression. Indeed, Zfra4-10 is potent in restoring memory loss in triple transgenic mice for AD (3xTg) by blocking the aggregation of amyloid beta 42 (Aβ42), enhancing degradation of aggregated proteins, and inhibiting activation of inflammatory NF-κB. In light of the findings, Zfra4-10-mediated suppression of cancer and AD is due, in part, to an enhanced binding of endogenous WWOX and its binding partners. In this perspective review article, we detail the molecular action of WWOX in the HYAL-2/WWOX/SMAD4 signaling for biological effects, and discuss WWOX phosphorylation forms in interacting with binding partners, leading to suppression of cancer growth and retardation of AD progression.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
While a broadband metamaterial perfect absorber (MPA) has been implemented and proposed intensively in recent years, an ultra-broadband perfect absorber with polarization selectivity has not been ...realized in literature. In this work, we propose a configuration of polarization-selective (PS) MPA with ultra-wide absorption bandwidth. The aluminum wire grid is integrated on top of the ultrathin-metal-dielectric stacking. The transverse electric (TE) wave is blocked due to the requirement of zero tangential electric field at the metal surface. The transverse magnetic field can pass the aluminum wire-grids because the normal electric field can be supported by the surface charge density at the metal surface, and full absorption of the TM wave is accomplished by the metal-dielectric stacking beneath. Theoretical calculation using rigorously coupled wave analysis demonstrates the wavelength selectivity from λ = 1.98μm to λ = 11.74μm where the TE absorption is <0.04 while TM absorption is >0.95, using 300 nm thick aluminum (Al) wire grid with 16-pair SiO
/Ti stacking. Additionally, the design is wavelength scalable by adjusting the dielectric thickness (t
) and the wire grid period (P) and height (t). The experimental result is demonstrated using Al grids and Ti/SiO
, and the measured result fully supports the calculated prediction.
WW domain containing oxidoreductase, designated WWOX, FOR or WOX1, is a known pro-apoptotic factor when ectopically expressed in various types of cancer cells, including glioblastoma multiforme ...(GBM). The activation of sonic hedgehog (Shh) signaling, especially paracrine Shh secretion in response to radiation, is associated with impairing the effective irradiation of cancer cells. Here, we examined the role of Shh signaling and WOX1 overexpression in the radiosensitivity of human GBM cells. Our results showed that ionizing irradiation (IR) increased the cytoplasmic Shh and nuclear Gli-1 content in GBM U373MG and U87MG cells. GBM cells with exogenous Shh treatment exhibited similar results. Pretreatment with Shh peptides protected U373MG and U87MG cells against IR in a dose-dependent manner. Cyclopamine, a Hedgehog/Smoothened (SMO) inhibitor, reversed the protective effect of Shh in U87MG cells. Cyclopamine increased Shh plus IR-induced H2AX, a marker of DNA double-strand breaks, in these cells. To verify the role of Shh signaling in the radiosensitivity of GBM cells, we tested the effect of the Gli family zinc finger 1 (Gli-1) inhibitor zerumbone and found that it could sensitize GBM cells to IR. We next examined the role of WOX1 in radiosensitivity. Overexpression of WOX1 enhanced the radiosensitivity of U87MG (possessing wild type p53 or WTp53) but not U373MG (harboring mutant p53 or MTp53) cells. Pretreatment with Shh peptides protected both WOX1-overexpressed U373MG and U87MG cells against IR and increased the cytoplasmic Shh and nuclear Gli-1 content. Zerumbone enhanced the radiosensitivity of WOX1-overexpressed U373MG and U87MG cells. In conclusion, overexpression of WOX1 preferentially sensitized human GBM cells possessing wild type p53 to radiation therapy. Blocking of Shh signaling may enhance radiosensitivity independently of the expression of p53 and WOX1. The crosstalk between Shh signaling and WOX1 expression in human glioblastoma warrants further investigation.
While there have been many studies using machine learning (ML) algorithms to predict process outcomes and device performance in semiconductor manufacturing, the extensively developed technology ...computer-aided design (TCAD) physical models should play a more significant role in conjunction with ML. While TCAD models have been effective in predicting the trends of experiments, a machine learning statistical model is more capable of predicting the anomalous effects that can be dependent on the chambers, machines, fabrication environment, and specific layouts. In this paper, we use an analytics-statistics mixed training (ASMT) approach using TCAD. Under this method, the TCAD models are incorporated into the machine learning training procedure. The mixed dataset with the experimental and TCAD results improved the prediction in terms of accuracy. With the application of ASMT to the BOSCH process, we show that the mean square error (MSE) can be effectively decreased when the analytics-statistics mixed training (ASMT) scheme is used instead of the classic neural network (NN) used in the baseline study. In this method, statistical induction and analytical deduction can be combined to increase the prediction accuracy of future intelligent semiconductor manufacturing.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Compared with conventional solar cells, thermophotovoltaics (TPV) can be more efficient and, thus, exceeds the detailed balance efficiency limit. In particular, the emitter of TPV is a critical ...design since it determines whether the thermalization loss can be reduced and whether the sub-band-gap radiation can be suppressed, as far as the photovoltaic (PV) process is concerned. In this paper, we propose a selective planar emitter composed of alternating ultrathin metal and dielectric layers. An aperiodic dielectric stacking is designed to tailor the emission spectrum by shaping the emission peak and by adjusting the emission wavelength. We show that the peak emission wavelength (λ emission ) is adjustable from λ = 1500 nm to λ = 2500 nm. Furthermore, the long-wavelength cutoff is very sharp for our proposed emitter structure, and the absorption is suppressed to 0.1 beyond the cutoff. The preliminary experiment is also conducted to fulfill the concept of a fully planar ultrathin refractory metal emitter design, and the result is similar to the calculated ones. We believe that the planar thermal emitter based on ultrathin metals and aperiodic dielectric stacking is very promising for future thermal emission applications since it requires no lithography and etching, provides strong peak emission power, and possesses wide wavelength scalability.
Hyaluronidase HYAL-2 is a membrane-anchored protein and also localizes, in part, in the lysosome. Recent study from animal models revealed that both HYAL-1 and HYAL-2 are essential for the metabolism ...of hyaluronan (HA).
deficiency is associated with chronic thrombotic microangiopathy with hemolytic anemia in mice due to over accumulation of high molecular size HA. HYAL-2 is essential for platelet generation. Membrane HYAL-2 degrades HA bound by co-receptor CD44. Also, in a non-canonical signal pathway, HYAL-2 serves as a receptor for transforming growth factor beta (TGF-β) to signal with downstream tumor suppressors WWOX and SMAD4 to control gene transcription. When SMAD4 responsive element is overly driven by the HYAL-2-WWOX-SMAD4 signaling complex, cell death occurs. When rats are subjected to traumatic brain injury, over accumulation of a HYAL-2-WWOX complex occurs in the nucleus to cause neuronal death. HA induces the signaling of HYAL-2-WWOX-SMAD4 and relocation of the signaling complex to the nucleus. If the signaling complex is overexpressed, bubbling cell death occurs in WWOX-expressing cells. In addition, a small synthetic peptide Zfra (zinc finger-like protein that regulates apoptosis) binds membrane HYAL-2 of non-T/non-B spleen HYAL-2
CD3
CD19
Z lymphocytes and activates the cells to generate memory anticancer response against many types of cancer cells
. Whether the HYAL-2-WWOX-SMAD4 signaling complex is involved is discussed. In this review and opinion article, we have updated the current knowledge of HA, HYAL-2 and WWOX, HYAL-2-WWOX-SMAD4 signaling, bubbling cell death, and Z cell activation for memory anticancer response.
In the past, perfect metamaterial absorbers (PMAs) have required nanolithography patterning to boost broadband absoprtion. Tapered structures, in particular, are shown to achieve close-to-unity ...absorption over broadband using adiabatic light coupling. A nontapered PMA is desirable due to the fact that it is easier to fabricate using regular lithography techniques. This facilitates the scalability to large-area photonic applications such as thermophotovoltaics. In this work, we propose a fully planarized design with ultrathin metallic films for broadband PMAs. The design provides close-to-unity absorbance over a wide spectral range and is wavelength scalable from middle ultraviolet to long wavelength infrared. The planarized design is extremely easy to fabricate, and it requires no lithography nor etching. The design can be used with different moderate-extinction metals such as tungsten, titanium, tantalum, and nickel. The physics is that the thin layer of the moderate-extinction metal allows photons to penetrate through itself. The insertion of the dielectric between thin metal layers is necessary to spatially separate the ultrathin metallic thin film to boost the effect of thin-film absorption. As far as the bandwidth normalized to center wavelength is concerned, we believe that the experimental result demonstrated here shows the broadest bandwidth to date.
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