Impact of pump-phase noise in PPLN-based optical parametric amplifier and wavelength converter for digital coherent transmission.

Wideband signal amplification and optical signal processing with a high gain using an optical parametric amplifier based on a periodically poled LiNbO3 (PPLN) waveguide is attractive for constructing wideband optical fiber networks. We experimentally investigate the transfer characteristics of the phase noise of a pump laser in χ(2)-based optical parametric amplification and wavelength conversion on the basis of second-harmonic-generation and differential-frequency-generation processes. We also evaluate the effect of the transferred phase noise on signal quality in dispersion-unmanaged digital coherent fiber transmission systems. We show that the phase noise is transferred only to the wavelength-converted idler and does not affect the amplified signal even by using a pump laser with a MHz-order linewidth. We also show that the phase noise transferred to the idler light can have a similar impact on signal quality as equalization-enhanced phase noise (EEPN) in digital coherent transmission. The signal penalty including EEPN was evaluated with several pump lasers and at symbol rates of 32, 64, and 96 Gbaud. We also propose a method of using correlated pump lights between a wavelength converter pair to cancel out the transfer of phase noise.

Comparison of Slow-Infusion Magnetic Resonance Angiography with Sequential K-Space Filling and Computed Tomography Angiography to Detect the Adamkiewicz Artery.

BACKGROUND: Radiographic detection of the Adamkiewicz artery (AKA) before aortic surgery helps to avoid spinal cord ischemia (SCI). We applied magnetic resonance angiography (MRA) using gadolinium enhancement (Gd-MRA) by means of the slow-infusion method with sequential k-space filling and compared AKA detectability with that of computed tomography angiography (CTA). METHODS: A total of 63 patients with thoracic or thoracoabdominal aortic disease (30 with aortic dissection [AD] and 33 with aortic aneurysm) who underwent both CTA and Gd-MRA to detect AKA were evaluated. The detectability of the AKA using Gd-MRA and CTA were compared among all patients and subgroups based on anatomical features. RESULTS: The detection rates of the AKAs using Gd-MRA and CTA were higher in all 63 patients (92.1% vs. 71.4%, P = 0.003). In AD cases, the detection rates using Gd-MRA and CTA were higher in all 30 patients (93.3% vs. 66.7%, P = 0.01) as well as in 7 patients whose AKA originated from false lumens (100% vs. 0%). In aneurysm cases, the detection rates using Gd-MRA and CTA were higher in 22 patients whose AKA originated from the nonaneurysmal parts (100% vs. 81.8%, P = 0.03). In clinical, SCI was observed in 1.8% of cases after open or endovascular repair. CONCLUSIONS: Despite the longer examination time and more complicated imaging techniques compared to those of CTA, the high spatial resolution of slow-infusion MRA may be preferable for detecting AKA before performing various thoracic and thoracoabdominal aortic surgeries.

Morphological changes in vertebral artery dissections observed on 4D flow magnetic resonance images: case report.

The morphology of vertebral artery (VA) dissections can change in the clinical course. A 58-year-old female with a 2-week headache was diagnosed with left VA dissection. Hemodynamic stress on the right VA detected on 4D flow MRI scans resulted in increased wall shear stress but the vessel was morphologically unchanged. Subsequent MRA revealed right VA dissection. Her bilateral dissections were treated conservatively and no neurological abnormality developed. Serial 4D flow MRI may be useful for observing morphological changes in VA dissections and help to clarify the mechanism(s) underlying VA dissections.

Impact of age-associated increase in 2'-O-methylation of miRNAs on aging and neurodegeneration in Drosophila.

MicroRNAs (miRNAs) are 20- to ∼24-nucleotide (nt) small RNAs that impact a variety of biological processes, from development to age-associated events. To study the role of miRNAs in aging, studies have profiled the levels of miRNAs with time. However, evidence suggests that miRNAs show heterogeneity in length and sequence in different biological contexts. Here, by examining the expression pattern of miRNAs by Northern blot analysis, we found that Drosophila miRNAs show distinct isoform pattern changes with age. Surprisingly, an increase of some miRNAs reflects increased 2'-O-methylation of select isoforms. Small RNA deep sequencing revealed a global increase of miRNAs loaded into Ago2, but not into Ago1, with age. Our data suggest increased loading of miRNAs into Ago2, but not Ago1, with age, indicating a mechanism for differential loading of miRNAs with age between Ago1 and Ago2. Mutations in Hen1 and Ago2, which lack 2'-O-methylation of miRNAs, result in accelerated neurodegeneration and shorter life span, suggesting a potential impact of the age-associated increase of 2'-O-methylation of small RNAs on age-associated processes. Our study highlights that miRNA 2'-O-methylation at the 3' end is modulated by differential partitioning of miRNAs between Ago1 and Ago2 with age and that this process, along with other functions of Ago2, might impact age-associated events in Drosophila.

Water-in-CO2 Microemulsions Stabilized by an Efficient Catanionic Surfactant.

To facilitate potential applications of water-in-supercritical CO2 microemulsions (W/CO2 µEs) efficient and environmentally responsible surfactants are required with low levels of fluorination. As well as being able to stabilize water-CO2 interfaces, these surfactants must also be economical, prevent bioaccumulation and strong adhesion, deactivation of enzymes, and be tolerant to high salt environments. Recently, an ion paired catanionic surfactant with environmentally acceptable fluorinated C6 tails was found to be very effective at stabilizing W/CO2 µEs with high water-to-surfactant molar ratios (W0) up to ∼50 (Sagisaka, M.; et al. Langmuir 2019, 35, 3445-3454). As the cationic and anionic constituent surfactants alone did not stabilize W/CO2 µEs, this was the first demonstration of surfactant synergistic effects in W/CO2 microemulsions. The aim of this new study is to understand the origin of these intriguing effects by detailed investigations of nanostructure in W/CO2 microemulsions using high-pressure small-angle neutron scattering (HP-SANS). These HP-SANS experiments have been used to determine the headgroup interfacial area and volume, aggregation number, and effective packing parameter (EPP). These SANS data suggest the effectiveness of this surfactant originates from increased EPP and decreased hydrophilic/CO2-philic balance, related to a reduced effective headgroup ionicity. This surfactant bears separate C6F13 tails and oppositely charged headgroups, and was found to have a EPP value similar to that of a double C4F9-tail anionic surfactant (4FG(EO)2), which was previously reported to be one of most efficient stabilizers for W/CO2 µEs (maximum W0 = 60-80). Catanionic surfactants based on this new design will be key for generating superefficient W/CO2 µEs with high stability and water solubilization.

[A Case of Advanced Gastric Cancer of an Elderly Patient Responding Effectively to Pembrolizumab].

A 96-year-old man was admitted to our hospital because of dysphagia. After examination, he was diagnosed with type 3 advanced gastric cancer in the antrum with duodenal invasion. A gastrojejunostomy was performed because of dissemination in the pelvic floor. He was put on pembrolizumab after surgery because the microsatellite instability test showed positive results. The therapeutic response was PR. Pembrolizumab can improve the outcomes in elderly patients with unresectable advanced gastric cancer.

[Case of Hyperammonemia Induced by High-Dose Fluorouracil].

A case of hyperammonemia induced by chemotherapy, including high-dose fluorouracil(5-FU), for advanced unresectable large intestinal cancer has been reported. This case involved an 81-year-old female who was diagnosed with pT4bcN2M1 (multiple hepatic metastases; stage Ⅳ; KRAS: mutant)after emergency surgery for sigmoid colon cancer and diffuse peritonitis. Post-operation, the 4 courses of mFOLFOX6 plus Bmab therapy was started for advanced unresectable recurrent large intestinal cancer; 48 hours later, she developed consciousness disorder(JCS Ⅲ-300). The disorder promptly disappeared after discontinuation of high-dose 5-FU. Because high-dose 5-FU was inferred to be the main cause of hyperammonemia, XELOX plus Bmab therapy was started as a post-treatment. She did not develop hyperammonemia; therefore, 8 courses were administered. The patient is being followed-up now.

The microRNA miR-34 modulates ageing and neurodegeneration in Drosophila.

Human neurodegenerative diseases have the temporal hallmark of afflicting the elderly population. Ageing is one of the most prominent factors to influence disease onset and progression, yet little is known about the molecular pathways that connect these processes. To understand this connection it is necessary to identify the pathways that functionally integrate ageing, chronic maintenance of the brain and modulation of neurodegenerative disease. MicroRNAs (miRNA) are emerging as critical factors in gene regulation during development; however, their role in adult-onset, age-associated processes is only beginning to be revealed. Here we report that the conserved miRNA miR-34 regulates age-associated events and long-term brain integrity in Drosophila, providing a molecular link between ageing and neurodegeneration. Fly mir-34 expression exhibits adult-onset, brain-enriched and age-modulated characteristics. Whereas mir-34 loss triggers a gene profile of accelerated brain ageing, late-onset brain degeneration and a catastrophic decline in survival, mir-34 upregulation extends median lifespan and mitigates neurodegeneration induced by human pathogenic polyglutamine disease protein. Some of the age-associated effects of miR-34 require adult-onset translational repression of Eip74EF, an essential ETS domain transcription factor involved in steroid hormone pathways. Our studies indicate that miRNA-dependent pathways may have an impact on adult-onset, age-associated events by silencing developmental genes that later have a deleterious influence on adult life cycle and disease, and highlight fly miR-34 as a key miRNA with a role in this process.

Optical pump phase locking to a carrier wave extracted from phase-conjugated twin waves for phase-sensitive optical amplifier repeaters.

In this paper, an optical phase-locked loop assisted by sum-frequency and second-harmonic generation (SS-OPLL) for frequency nondegenerate optical parametric phase-sensitive amplifier repeaters is experimentally demonstrated. First, theoretical derivations show that carrier extraction from phase-conjugated twin waves (PCTWs) and reference light generation are achieved by sum-frequency generation; therefore, the SS-OPLL circuit enables optical phase locking between PCTWs and a pump wave by a simple architecture based on a balanced OPLL. Then, optical phase locking between 20-Gbit/s quadrature phase-shift keying PCTWs and an individual pump source is experimentally demonstrated. Experimental results indicate that phase errors were reduced during the SS-OPLL operation.

Simultaneous nonlinearity mitigation in 92 × 180-Gbit/s PDM-16QAM transmission over 3840 km using PPLN-based guard-band-less optical phase conjugation.

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.

Rapid spectrum measurement at 3 µm over 100 nm wavelength range using mid-infrared difference frequency generation source.

We demonstrate a broadband rapid scanning light source in the 3-µm region by using difference frequency generation (DFG). The DFG source consists of a module with quasi-phase-matched LiNbO3 ridge waveguides, a 1-µm-band wide swept range laser for the pump source, and a 1.5-µm continuous wave laser for the signal source. The sweep rate and the tuning bandwidth of this source are 20 kHz and 100 nm, respectively. This source enables us to evaluate the temperature dependence of absorbance of methane gas.

Dual wavelength 3.2-µm source for isotope ratio measurements of (13)CH(4)/(12)CH(4).

Difference frequency generation using one 1.58-µm and two 1.06-µm distributed feedback Bragg-grating laser diodes and a ridge-type PPLN alternately provide two 3.2-µm coaxial waves resonant with individual isotopic transitions separated by 13 cm(-1). The ν(3) band R(6) A(2) allowed transition of (13)CH(4) and the ν(3) band R(6) A(2) weakly allowed transition of (12)CH(4) are an ideal pair for isotope ratio measurements. The (13)CH(4)/(12)CH(4) isotope ratio is determined for three sample gases with a relative uncertainty of 0.7 ‰, and it is confirmed that the temperature dependence is smaller than the uncertainty.

Sub-Doppler resolution mid-infrared spectroscopy using a difference-frequency-generation source spectrally narrowed by laser linewidth transfer.

The spectral linewidth of a 3.28 µm difference-frequency-generation source has been reduced to 3.5 kHz using a laser linewidth transfer technique [Opt. Express21, 7891 (2013)]. We use an optical frequency comb with a broad servo bandwidth to transfer a narrow linewidth of a pump laser, a 1.06 µm Nd:YAG laser, to a signal laser, a 1.57 µm external-cavity laser diode. This source enables us to record the Lamb dip of the ν3 band R(2) E transition of methane with a molecular spectral linewidth of 21 kHz while the frequency axis is absolutely calibrated.

Design of cavity-enhanced absorption cell for reducing transit-time broadening.

To reduce the linewidth of Lamb dips, we introduce a cavity-enhanced absorption cell (CEAC) coupled with a Gaussian beam with a 1.9-mm 1/e(2) radius at the beam waist for the reduction of transit-time broadening. We state that transit-time broadening depends only on the beam radius at the beam waist. This fact is useful for the design of the CEAC, and a pair of concave and convex mirrors is thereby employed. We have carried out sub-Doppler resolution spectroscopy of the ν(3) band of CH(4) and the ν(1) band of CH(3)D using a difference-frequency-generation source and the CEAC, and the recorded Lamb dips narrow to 80 kHz (HWHM).

A biochemical study of the distribution of collagen and its crosslinks in knee ligaments and the patellar tendon.

PURPOSE: The purpose of this study was to investigate biochemical differences in collagen crosslinks from different locations within the ligaments and a tendon of the human knee. MATERIALS AND METHODS: The anterior cruciate ligament (ACL), posterior cruciate ligament (PCL), medial collateral ligament (MCL), lateral collateral ligament (LCL), and patellar tendon (PT) were obtained from 24 cadavers (13 men and 11 women) whose average age at the time of death was 84.8 years. Ligaments and PT samples were obtained from the femoral and tibial insertions and the midsubstance. Hydroxyproline (Hyp) and collagen crosslinks, including pyridinoline (Pyr) and pentosidine (Pen), were compared among the different sites. RESULTS: The midsubstance Hyp concentration was greater than at the femoral and tibial insertions in the ACL (p = 0.00124 and 0.000255, respectively) and PCL (p = 0.00036 and 0.042, respectively). The Pyr:collagen ratio did not differ among sites in any of the ligaments or PT. The Pen:collagen ratio at the midsubstance was greater than at the femoral and tibial insertions in the ACL (p = 0.00022 and 0.00025, respectively) and LCL (p = 0.000081 and 0.000021, respectively) and was greater at the femoral insertion in the MCL (p = 0.00010). CONCLUSIONS: The mature collagen crosslink Pyr was not different in distribution in knee ligaments and the PT. Pen increased at the midsubstance ligaments and the PT. As increased Pen may represent ligament degeneration, this may indicate that degeneration may progress more rapidly at the midsubstance than at the insertion sites of a ligament.

[Second-line FOLFIRI plus bevacizumab for patients with metastatic colorectal cancer after resection of the primary lesion].

The efficacy and safety of bevacizumab(BV), combined with infusional 5-fluorouracil/leucovorin(5-FU/LV)plus irinotecan(FOLFIRI)as the second-line treatment for metastatic colorectal cancer(mCRC)after resection of the primary lesion, have not been fully clarified. We examined clinical results of 35 patients on BV plus FOLFIRI at our hospital, and investigated the efficacy of BV plus FOLFIRI in mCRC patients who failed oxaliplatin-containing regimens(26 patients were treated with BV at a dose of 5mg/kg, 3 patients with BV 10mg/kg, and 6 patients had BV increased from 5mg/kg to 10mg/kg). The average frequency of BV plus FOLFIRI treatment was 13. 9 times, and the average length of treatment was 10. 0 months. The overall response rate was 17. 1%(CR 1 patient, PR 5 patients, SD 21 patients, PD 8 patients). The median PFS was 11. 0 months for FOLFIRI plus BV after first-line chemotherapy, and the median OS was 23. 0 months. The adverse events were 77. 1%(>Grade 3, 55. 5%)and the BV-associated adverse event was grade 3 hypertension(2 patients). The FOLFIRI plus BV regimen is an active and well-tolerated second-line chemotherapy treatment for patients with mCRC after resection of the primary lesion.

Genetic and functional odorant receptor variation in the Homo lineage.

Humans, Neanderthals, and Denisovans independently adapted to a wide range of geographic environments and their associated food odors. Using ancient DNA sequences, we explored the in vitro function of thirty odorant receptor genes in the genus Homo. Our extinct relatives had highly conserved olfactory receptor sequence, but humans did not. Variations in odorant receptor protein sequence and structure may have produced variation in odor detection and perception. Variants led to minimal changes in specificity but had more influence on functional sensitivity. The few Neanderthal variants disturbed function, whereas Denisovan variants increased sensitivity to sweet and sulfur odors. Geographic adaptations may have produced greater functional variation in our lineage, increasing our olfactory repertoire and expanding our adaptive capacity. Our survey of olfactory genes and odorant receptors suggests that our genus has a shared repertoire with possible local ecological adaptations.

Antagonistic interactions between odorants alter human odor perception.

The olfactory system uses hundreds of odorant receptors (ORs), the largest group of the G-protein-coupled receptor (GPCR) superfamily, to detect a vast array of odorants. Each OR is activated by specific odorous ligands, and like other GPCRs, antagonism can block activation of ORs. Recent studies suggest that odorant antagonisms in mixtures influence olfactory neuron activities, but it is unclear how this affects perception of odor mixtures. In this study, we identified a set of human ORs activated by methanethiol and hydrogen sulfide, two potent volatile sulfur malodors, through large-scale heterologous expression. Screening odorants that block OR activation in heterologous cells identified a set of antagonists, including ß-ionone. Sensory evaluation in humans revealed that ß-ionone reduced the odor intensity and unpleasantness of methanethiol. Additionally, suppression was not observed when methanethiol and ß-ionone were introduced simultaneously to different nostrils. Our study supports the hypothesis that odor sensation is altered through antagonistic interactions at the OR level.

WAVY LEAF1, an ortholog of Arabidopsis HEN1, regulates shoot development by maintaining MicroRNA and trans-acting small interfering RNA accumulation in rice.

In rice (Oryza sativa), trans-acting small interfering RNA (ta-siRNA) is essential for shoot development, including shoot apical meristem (SAM) formation and leaf morphogenesis. The rice wavy leaf1 (waf1) mutant has been identified as an embryonic mutant resembling shoot organization1 (sho1) and sho2, homologs of a loss-of-function mutant of DICER-LIKE4 and a hypomorphic mutant of ARGONAUTE7, respectively, which both act in the ta-siRNA production pathway. About half of the waf1 mutants showed seedling lethality due to defects in SAM maintenance, but the rest survived to the reproductive phase and exhibited pleiotropic phenotypes in leaf morphology and floral development. Map-based cloning of WAF1 revealed that it encodes an RNA methyltransferase, a homolog of Arabidopsis (Arabidopsis thaliana) HUA ENHANCER1. The reduced accumulation of small RNAs in waf1 indicated that the stability of the small RNA was decreased. Despite the greatly reduced level of microRNAs and ta-siRNA, microarray and reverse transcription-polymerase chain reaction experiments revealed that the expression levels of their target genes were not always enhanced. A double mutant between sho and waf1 showed an enhanced SAM defect, suggesting that the amount and/or quality of ta-siRNA is crucial for SAM maintenance. Our results indicate that stabilization of small RNAs by WAF1 is indispensable for rice development, especially for SAM maintenance and leaf morphogenesis governed by the ta-siRNA pathway. In addition, the inconsistent relationship between the amount of small RNAs and the level of the target mRNA in waf1 suggest that there is a complex regulatory mechanism that modifies the effects of microRNA/ta-siRNA on the expression of the target gene.

[Current state of treatment for advanced gastric cancer].

The radical treatment of gastric cancer is complete resection of the tumor by surgery. For advanced gastric cancer, a multidisciplinary approach has been attempted to improve patient prognosis. Potentially resectable and curable advanced gastric cancer is treated with routine surgery, followed by postoperative adjuvant chemotherapy. For highly advanced gastric cancer, extended radical surgery or preoperative adjuvant chemotherapy have been attempted. Laparoscopic gastrectomy for advanced gastric cancer has not been widely used because of the difficult surgical technique involved, but enhanced magnification in the surgical field is expected to improve the accuracy of the lymph node dissection procedure. In future, the significance of currently available treatments should be investigated. The key treatment for advanced gastric cancer at present is surgery.