ABSTRACT
The prevalent human pathogen, mumps virus (MuV; orthorubulavirus parotitidis) causes various complications and serious sequelae, such as meningitis, encephalitis, deafness, and impaired fertility. Direct-acting antivirals (DAAs) targeting MuV which can prevent mumps and mumps-associated complications and sequelae are yet to be developed. Paramyxoviridae family members, such as MuV, possess viral surface hemagglutinin-neuraminidase (HN) protein with sialidase activity which facilitates efficient viral replication. Therefore, to develop DAAs targeting MuV we synthesized MuV sialidase inhibitors. It is proposed that the viral HN has a single functional site for N-acetylneuraminic acid (Neu5Ac) binding and sialidase activity. Further, the known MuV sialidase inhibitor is an analog of Neu5Ac-2,3-didehydro-2-deoxy-N-acetylneuraminic acid (DANA)-which lacks potency. DANA derivatives with higher MuV sialidase inhibitory potency are lacking. The MuV-HN-Neu5Ac binding site has a hydrophobic cavity adjacent to the C4 position of Neu5Ac. Exploiting this, here, we synthesized DANA derivatives with increasing hydrophobicity at its C4 position and created 3 novel sialidase inhibitors (Compounds 1, 2 and 3) with higher specificity for MuV-HN than DANA; they inhibited MuV replication step to greater extent than DANA. Furthermore, they also inhibited hemagglutination and the MuV infection step. The insight-that these 3 novel DANA derivatives possess linear hydrocarbon groups at the C4-hydroxyl group of DANA-could help develop highly potent sialidase inhibitors with high specificity for MuV sialidase, which may function as direct-acting MuV-specific antivirals.
ABSTRACT
Equine influenza virus strains of Florida sublineage clade 1 (Fc1) have been circulating in North America. In this study, virus neutralization assays were performed to evaluate antigenic differences between Fc1 vaccine strains and North American Fc1 strains isolated in 2021-2022, using equine antisera against A/equine/South Africa/4/2003 (a vaccine strain recommended by the World Organisation for Animal Health) and A/equine/Ibaraki/1/2007 (a Japanese vaccine strain). Antibody titers against four North American Fc1 strains isolated in 2021-2022 were comparable to those against the homologous vaccine strains. These results suggest that current Fc1 vaccine strains are effective against North American strains from 2021-2022.
Subject(s)
Horse Diseases , Influenza A Virus, H3N8 Subtype , Influenza Vaccines , Orthomyxoviridae Infections , Vaccines , Animals , Horses , Florida , North AmericaABSTRACT
We propose a high-throughput and precise waveguide-dimensional-measurement method consisting of a generative adversarial network (GAN) and curve-fitting-based dimensional calculator using sidewall functions. The GAN can learn the differences between low-magnification (LM) and high-magnification (HM) optical microscope images taken with different objective lenses at different magnifications over the same area. The LM and HM images of the waveguides are captured using an optical microscope at magnifications of 500× and 2000×, respectively. We obtained a standard deviation of the waveguide widths of approximately 0.8 pixels (â¼ 42â nm), and confirmed precise width measurement using super-resolution images at the same imaging throughput as with an LM microscope.
ABSTRACT
While ultrahigh-baud-rate optical signals are effective for extending the transmission distance of large capacity signals, they also reduce the number of wavelengths that can be arranged in a band because of their wider bandwidth. This reduces the flexibility of optical path configuration in reconfigurable optical add/drop multiplexing (ROADM) networks. Particularly in colorless, directionless and contentionless (CDC)-ROADM, the effect reduces the add/drop ratio at a node. Multiband ROADM systems are an effective countermeasure for overcoming this issue, but they make the node configuration more complicated and its operation more difficult. In this paper, we analyze the challenges of C + L band CDC-ROADM and show that optical switch devices that operate over multiple bands are effective in meeting them. For this purpose, we built a C + L band CDC-ROADM node based on C + L band wavelength-selective switches and multicast switches and confirmed its effectiveness experimentally. In particular, to simplify the node configuration, we propose a reduction in the number of optical amplifiers used for node loss compensation and experimentally verify its feasibility.
ABSTRACT
Vertebrate Hox clusters are comprised of multiple Hox genes that control morphology and developmental timing along multiple body axes. Although results of genetic analyses using Hox-knockout mice have been accumulating, genetic studies in other vertebrates have not been sufficient for functional comparisons of vertebrate Hox genes. In this study, we isolated all of the seven hox cluster loss-of-function alleles in zebrafish using the CRISPR-Cas9 system. Comprehensive analysis of the embryonic phenotype and X-ray micro-computed tomography scan analysis of adult fish revealed several species-specific functional contributions of homologous Hox clusters along the appendicular axis, whereas important shared general principles were also confirmed, as exemplified by serial anterior vertebral transformations along the main body axis, observed in fish for the first time. Our results provide insights into discrete sub/neofunctionalization of vertebrate Hox clusters after quadruplication of the ancient Hox cluster. This set of seven complete hox cluster loss-of-function alleles provide a formidable resource for future developmental genetic analysis of the Hox patterning system in zebrafish.
Subject(s)
Genes, Homeobox/genetics , Multigene Family , Zebrafish/genetics , Zebrafish/physiology , Animals , CRISPR-Cas Systems , Embryonic Development/genetics , Evolution, Molecular , Female , Gene Duplication , Gene Expression Regulation, Developmental , Male , Mutation , Skeleton/anatomy & histology , Skeleton/growth & development , Species Specificity , X-Ray Microtomography , Zebrafish/embryologyABSTRACT
We propose a waveguide frontend with integrated polarization diversity optics for a wavelength selective switch (WSS) array with a liquid crystal on silicon switching engine to simplify the free space optics configuration and the alignment process in optical modules. The polarization diversity function is realized by the integration of a waveguide-type polarization beam splitter and a polarization rotating half-wave plate in a beam launcher using silica-based planar lightwave circuit technology. We confirmed experimentally the feasibility of using our proposed waveguide frontend in a two-in-one 1 × 20 WSS. The experimental results show that the fabricated waveguide frontend provides a polarization diversity function without any degradation in optical performance.
ABSTRACT
We propose a novel simple space division multiplexing (SDM) node which is rearrangeble nonblocking, and effectively utilizes enhanced network resources through SDM. The proposed node can reduce a number of ports of wavelength selective switches (WSSs) and a number of WSS modules by modifying conventional multi-stage switches and employing integrated multiple arrayed WSSs. We experimentally actualized the newly proposed node, and demonstrate wavelength, core, and direction switching functions based on 127-Gbps Dual Polarization Quadrature Phase Shift Keying (DP-QPSK) signals. We also confirm the feasibility of the proposed SDM node through SDM transmission experiments using a 40-km multicore fiber and a multicore amplifier.
ABSTRACT
We experimentally demonstrated the simultaneous nonlinearity mitigation of PDM-16QAM WDM signals using complementary-spectrally-inverted optical phase conjugation (CSI-OPC). We achieved reserved-band-less, guard-band-less, and polarization independent OPC based on periodically poled LiNbO3 waveguides. By employing the CSI-OPC, 2.325-THz-band (93 × 25 GHz) complementary spectral inversion was achieved while retaining the original WDM bandwidth. A Q2-factor improvement of over 0.4 dB and a 5120 km transmission with a Q2-factor above the FEC limit were confirmed using a 10-channel WDM transmission at the signal band center and signal band edge. We then demonstrated the mitigation of the nonlinear impairments in a 3840 km long-haul WDM signal transmission for all 92-channel 180-Gbit/s PDM-16QAM quasi-Nyquist-WDM signals.
ABSTRACT
ß-Catenin signaling plays a pivotal role in the genesis of a variety of malignant tumors, but its role in breast cancer has not been fully elucidated. Here, we examined whether deregulation of ß-catenin signaling is related to the aggressive characteristics of certain types of breast cancers. Analysis of cytokine levels in MDA-MB-231 cells overexpressing a constitutively active form of ß-catenin (CAß-catenin) revealed a higher level of CCL5 expression. Cells transfected with CAß-catenin or stimulated with recombinant CCL5 exhibited increased cell invasion activity and spheroid formation in vitro. Furthermore, CAß-catenin-transfected MDA-MB-231 cells formed larger tumor masses that contained more Ki-67-positive cells and infiltrating lymphocytes than did the control cells. An inhibitor of CCR5 and a pan-CXCR neutralizing antibody dramatically reduced CAß-catenin-promoted activities. In addition to CCL5, 6-BIO, a chemical activator of ß-catenin, induced cell invasion and spheroid formation in MDA-MB-231 cells. Furthermore, high levels of nuclear ß-catenin accumulation were detected in breast cancer in patients with metastasis but not in those without metastasis. Nuclear ß-catenin localization is related to increased CCL5 production in breast cancer. These findings suggest that ß-catenin expression enhances tumor progression via chemokine production in breast cancers and that ß-catenin signaling is a critical regulator of the aggressive traits of breast cancers.
Subject(s)
Breast Neoplasms/metabolism , Chemokine CCL5/metabolism , Active Transport, Cell Nucleus , Animals , Breast Neoplasms/pathology , Cell Line, Tumor , Female , Humans , Mice, Nude , Neoplasm Transplantation , Up-Regulation , Wnt Signaling Pathway , beta CateninABSTRACT
For the development of the excimer probe responsible for DNA target, the deoxyuridine phosphoramidite derivative bearing the silylated pyrene attached at the C-5 position was prepared and incorporated into oligonucleotides. The modified oligonucleotides showed the excimer emission in the absence of the target DNA, on the other hands, the excimer emission was quenched in the presence of the target DNA. For the utilization of the fluorescence behavior, the novel molecular beacon probe containing the silylated pyrene-modified nucleoside at the stem region was designed and the fluorescence property of the probe found to show the responsibility for DNA target.
Subject(s)
DNA/analysis , Deoxyuridine/chemistry , Drug Design , Fluorescent Dyes/chemistry , Oligonucleotide Probes/chemistry , Organophosphorus Compounds/chemistry , Pyrenes/chemistry , Fluorescent Dyes/chemical synthesis , Molecular Structure , Oligonucleotide Probes/chemical synthesisABSTRACT
We propose arrayed optical amplifiers that share a single pump laser with the aim of realizing full-add/drop colorless, directionless, contentionless ROADM nodes and demonstrate its feasibility in experiments. The experimental results show that the fabricated arrayed optical amplifiers can be made to correspond properly to wavelength path reconfigurations by adjusting a splitting ratio of the variable splitter between the pump laser and eight EDFAs, and cause no significant penalty for 128-Gbit/s PDM-QPSK signal transmission.
ABSTRACT
We propose and demonstrate a multi-channel tunable optical dispersion compensator (TODC) that consists of an arrayed-waveguide grating (AWG) and liquid crystal on silicon (LCOS). By utilizing the AWG with a large angular dispersion and the LCOS with a flexible phase setting, we can construct a compact and flexible TODC that has a wide tuning range of chromatic dispersion. We confirmed experimentally that the TODC could realize channel-by-channel CD compensation for six WDM channels with a ± 800 ps/nm range and a 3 dB bandwidth of 24 GHz. We believe that the multi-channel operation of this TODC will help to reduce the cost and power consumption of high-speed optical transmission systems.
ABSTRACT
New anticancer drugs have been developed, and prediction of their effect is needed to perform tailor made chemotherapy. We investigated a selection of the predictive markers for oral adjuvant chemotherapy among 5-fluorouracil (5-FU) related genes. 5-FU related genes were examined by using a laser captured microdissection and real-time RT-PCR in 220 patients with invasive breast cancer. Sixty-six patients were treated with postoperative oral fluorouracil derivatives for 12 months or more, and we examined the prognosis of these patients according to the expression of 5-FU related genes. The median of thymidylate synthase (TS), dehydropyrimidine dehydrogenase (DPD), thymidine phosphorylase (TP) and orotate phosphoribosyltransferase (OPRT) mRNA values in the 220 specimens were determined for cut-off levels separating low and high gene expression. In 66 patients, 5-year disease-free survival (DFS) in the TP-high group (n=28) was significantly better than that in the TP-low group (n=38) (P=0.016). Of 220 patients, the 69 patients in TP-high group comprised 28 patients treated with oral fluorouracil derivatives and 41 patients with hormone therapy alone. The proportion of patients with lymph node involvement in the fluorouracil group was significantly greater than that in the hormone therapy alone group (P=0.003). Five-year DFS was not significantly different between the groups (P=0.80). Our results suggest that adjuvant oral fluorouracil chemotherapy may improve the prognosis of the patients with TP high expression breast cancer, and TP mRNA level in breast cancer may predict the effect of new oral fluorouracil derivatives for postoperative adjuvant chemotherapy.
Subject(s)
Breast Neoplasms/drug therapy , Fluorouracil/therapeutic use , Administration, Oral , Adult , Aged , Aged, 80 and over , Breast Neoplasms/metabolism , Breast Neoplasms/mortality , Chemotherapy, Adjuvant , Dihydrouracil Dehydrogenase (NADP)/genetics , Disease-Free Survival , Female , Fluorouracil/analogs & derivatives , Fluorouracil/metabolism , Humans , Middle Aged , Orotate Phosphoribosyltransferase/genetics , RNA, Messenger/analysis , Thymidine Phosphorylase/genetics , Thymidylate Synthase/geneticsABSTRACT
The correlations between mRNA expressions of 5-fluorouracil(5-FU)-related enzymes; thymidylate synthase(TS), dihydropyrimidine dehydrogenase(DPD), thymidine phosphorylase(TP), and orotate phosphoribosyltransferase (OPRT)in breast cancers, along with disease-free survival(DFS), were investigated in 35 patients treated with postoperative adjuvant chemotherapy using cyclophosphamide, methotrexate and 5-fluorouracil(CMF). The patients treated with CMF were divided into two groups, a lower group(L group)and a higher group(H group), according to the median value of the mRNA expression for each enzyme in 220 breast cancer specimens, which were resected between 1996 and 1998 in our institute. 5-year DFS was not significantly different between TS-L and H group(60% and 80%, p=0.38), DPD-L and H group(57.9% and 86.7%, p=0.088), and TP-L and H group(70% and 73.3%, p=0.89), respectively. 5-year DFS in the OPRT-H group(88.9%)was significantly better than that in the OPRT-L group(50%) (p=0.024). In the OPRT-H group, despite the fact that the proportion of patients with lymph node involvement in the CMF group was significantly higher than that in the postoperative adjuvant hormone therapy group, 5-year DFS was not significantly different between the two groups(p=0.10). Our results suggest that OPRT level was the significant predictive marker for DFS in the breast cancer patients treated with postoperative adjuvant chemotherapy using CMF.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Breast Neoplasms/drug therapy , Breast Neoplasms/genetics , Fluorouracil/therapeutic use , Adult , Aged , Aged, 80 and over , Breast Neoplasms/metabolism , Chemotherapy, Adjuvant , Cisplatin/therapeutic use , Disease-Free Survival , Female , Hormone Replacement Therapy , Humans , Methotrexate/therapeutic use , Middle Aged , RNA, Messenger/genetics , Treatment OutcomeABSTRACT
Because nipple discharge is caused by carcinoma as well as benign disease, identification of intraductal abnormalities with ductography is important. Ductography is an invasive mammographic examination in which contrast material is injected directly into the duct. Failure to cannulate or extravasation may occur. Ductography shows evidence of lesions, such as filling defects, duct obstruction, or wall irregularity, but it does not reveal the lesion itself. Furthermore, ductography produces a two-dimensional image, so it does not show the shape of the dilated duct or the precise location of the intraductal lesion in the breast. We applied three-dimensional (3D) heavily T2-weighted imaging with fat suppression of the breast to produce MR ductography. The dilated ducts are seen in 3D as tubular structures with high signal, and intraductal abnormalities are seen as signal defects. Furthermore, MR ductography can show an obstructed duct that cannot be seen on ductography. We also performed 3D breast MRI with the intravenous infusion of contrast material to show the lesion itself. Finally, we fused these 2 volume images into a single 3D fused image that not only shows the existence of intraductal abnormality, but reveals the shape, size, and extent of lesion, allowing us to understand easily the relationship between the ducts with dilation and any intraductal lesions in the breast. We herein introduce and describe this noninvasive method and discuss various factors related to its diagnostic use.
Subject(s)
Magnetic Resonance Imaging , Mammography , Nipples/diagnostic imaging , Nipples/pathology , Breast Neoplasms/diagnosis , Carcinoma, Ductal, Breast/diagnosis , Contrast Media/administration & dosage , Dilatation, Pathologic/diagnosis , Female , Humans , Image Processing, Computer-Assisted , Infusions, Intravenous , Papilloma, Intraductal/diagnosis , Sensitivity and Specificity , Ultrasonography, MammaryABSTRACT
We demonstrate and characterize symmetric [3x3] three-dimensional directional couplers fabricated in glass using a high-pulse energy femtosecond laser oscillator. The characteristics of the [3x3] directional couplers closely agree with the theoretical prediction, except for small errors caused by the fabrication process. We show that deviations from symmetry are dominated by vertical position errors of the coupling waveguide.
ABSTRACT
We propose a novel method for reducing the diffraction loss in an arrayed-waveguide grating. Our method introduces an interference fringe at the interface between slab and arrayed waveguides to relax the mode mismatch between them. We achieved a loss reduction of more than 0.42 dB with this method. Moreover, we provide an explanation of the loss-reduction mechanism of our method in terms of the point of imaging property of light.