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In the social amoeba Dictyostelium discoideum, the polyketide MPBD (4-methyl-5-pentylbenzene-1,3-diol) regulates the gene expressions of cAMP signaling to make cells aggregation-competent and also induces spore maturation. The polyketide synthase StlA is responsible for MPBD biosynthesis in D. discoideum and appears to be conserved throughout the major groups of the social amoeba (Dictyostelia). In this study, we analyzed the function of StlA in Polysphondylium violaceum by identifying the gene sequence and creating the knockout mutants. We found that Pv-stlA– mutants had defects only in cell aggregation but not in spore maturation, indicating that the function of StlA in inducing spore maturation is species-specific. We also found that MPBD could rescue the aggregation defect in Pv-stlA– mutants whereas the mutants normally exhibited chemotaxis to their chemoattractant, glorin. Our data suggest that StlA is involved in inducing aggregation in P. violaceum by acting on signaling pathways other than chemotaxis in P. violaceum.

Funding Acknowledgements Type of funding sources: None. Background Visually guided laser balloon (VGLB) has proven ample efficacy in achieving durable pulmonary vein (PV) isolation (PVI). Though the isolation area post-cryoballoon ablation has been reported to regress at the chronic phase, the shrinkage of the isolation area using VGLB during the chronic phase has not been described. Purpose This study aims to evaluate the differences in isolation areas created by VGLB between the acute and chronic phases using a high-resolution mapping system. Methods We assessed 26 patients who underwent a second procedure due to atrial fibrillation recurrence. Of them, 8 patients were treated with the third-generation VGLB and 18 patients were treated with the first-generation VGLB at the first session. In all patients, the voltage maps were created with high-resolution mapping catheters just after PVI (acute phase) and during the second session (chronic phase). With each map, the isolation area ( Results The isolation areas were re-evaluated at 8.3±6.6 months after the initial procedure. Twenty patients (76.9%) preserved persistent isolation lesions of all four PVs. Of them, the reduction of the isolation areas on the left- and right-sided PV antrum were 1.6±3.2 cm² (10.7±23.1% of the acute phase) and 4.8±3.6 cm² (27.8±18.9%), respectively. The analysis of the results revealed that the isolation area of the right-sided PV antrum yielded statistical shrinkage during the chronic phase (P=0.001), even though the electrical isolation was preserved. Conclusion After VGLB ablation, the isolation area of the right-sided PV antrum significantly regressed at the chronic phase, while the rate of durable PVI was high in line with the previous report.

Background Difficulties related to eating are often reported in children born preterm. The objective of this study was to quantitatively synthesize available data on the prevalence of problematic feeding in children under 4 years of age who were born preterm. Methods Literature was identified from PubMed, CINAHL, and PsycInfo. The search was limited to English language and publication years 2000–2020. To be included in the meta-analysis, the article had to report the prevalence of problematic oral feeding within a population of children born prematurely ( Results There were 22 studies that met inclusion criteria. Overall prevalence of problematic feeding (N = 4381) was 42% (95% CI 33–51%). Prevalence was neither significantly different across categories of gestational age nor by child age at the time of study. Few studies used psychometrically-sound assessments of feeding. Conclusion Problematic feeding is highly prevalent in prematurely-born children in the first 4 years of life regardless of degree of prematurity. Healthcare providers of children born preterm should consider screening for problematic feeding throughout early childhood as a potential complication of preterm birth. Systematic review registration number Not applicable.

Background and Aims: In gastrointestinal neuroendocrine tumors (GI-NETs), tumor size and grading based on cellular proliferative ability indicate biological malignancy but not necessarily clinically efficient prognostic stratification. We analyzed tumor size- and grading-based prevalence of lymphovascular invasion in GI-NETs to establish whether these are true biological malignancy indicators. Methods: We included 155 cases (165 lesions), diagnosed histologically with GI-NETs, that had undergone endoscopic or surgical resection. Patient age, sex, method of treatment, tumor size, invasion depth, lymphovascular invasion positivity according to Ki-67 index-based neuroendocrine tumor grading, distant metastases, and outcome were evaluated. The primary endpoints were the prevalence of lymphovascular invasion according to tumor size and grading. Results: Overall, 24.8% were positive for lymphovascular invasion. There was a high rate of lymphovascular invasion positivity even among grade 1 cases (22.8%). The rate of lymphovascular invasion was 3.4% for grade 1 cases Conclusions: GI-NETs ≤10 mm had a lymphovascular invasion prevalence exceeding 10%. The lymphovascular invasion impact in GI-NET development is incompletely understood, but careful follow-up, including consideration of additional surgical resection, is crucial in cases with lymphovascular invasion.

Background/Aim: Malignant lymphoma (ML) cases with overlapping gastrointestinal (GI) lesions are often encountered. We aimed to elucidate the importance of examining the GI tract in patients with ML and assess the overlap rate. Patients and Methods: We analysed 190 patients diagnosed with GI MLs. We compared the overlap rates among the different histopathological types. Results: Twenty-five (13.2%) patients had overlapping GI lesions in more than two segments. The overlap rates were 100% in mantle cell lymphomas (MCL), 27.6% in follicular lymphomas (FL), and 16.3% in diffuse large B-cell lymphomas (DLBCL). MCL, FL, and DLBCL cases showed significantly higher overlap rates than mucosa-associated lymphoid tissue lymphoma cases (p

The newly developed low-cost micro-electro-mechanical system (MEMS)-based acceleration sensors exhibit sufficient accuracy and stability to monitor the shaking of structures caused by an earthquake. We have developed a practical shaking-monitoring system using MEMS-based acceleration sensors and a 920 MHz multi-hop radio communication method that offers reliable radio wave communication, even within buildings. In this system, the base clock of each sensor unit must be closely synchronized to the master clock to minimize acceleration-induced phase synchronization error. In the proposed system, this error can be limited to three milliseconds in a system of multiple sensor units.

Main text Under the auspices of the Protein Analysis Working Group (PAWG) of the Comité Consultatif pour la Quantité de Matière (CCQM) a key comparison, CCQM-K115.2018, was coordinated by the Bureau International des Poids et Mesures (BIPM), the Health Sciences Authority (HSA) of Singapore and the Chinese National Institute of Metrology (NIM). Ten Metrology Institutes or Designated Institutes and the BIPM participated. Participants were required to assign the mass fraction of the hexapeptide of HbA0 (VE) present as the main component in the comparison sample for CCQM-K115.2018. The comparison samples were prepared by HSA/BIPM from synthetic VE purchased from a commercial supplier and used as provided without further treatment or purification. VE was selected to be representative of the performance of a laboratory's measurement capability for the purity assignment of chemically synthesized peptides of known sequence, without cross-links, up to 5 kDa and without modification. It was anticipated to provide an analytical measurement challenge representative for the value-assignment of compounds of broadly similar structural characteristics. The majority of participants used amino acid analysis (PICAA) with a correction for structurally-related peptide impurities approach as the amount of material that had been provided to each participant (25 mg) was insufficient to perform a full mass balance based characterization of the material by a participating laboratory. The coordinators, the BIPM, the HSA and the NIM, were the laboratories to use the mass balance approach as they had more material available. It was decided to propose KCRVs for both the VE mass fraction and the mass fraction of the peptide related impurities as indispensable contributor regardless of the use of PICAA, mass balance or any other approach to determine the VE purity. This allowed participants to demonstrate the efficacy of their implementation of the approaches used to determine the VE mass fraction. In particular, it allowed participants to demonstrate the efficacy of their implementation of peptide related impurity identification and quantification. More detailed studies on the identification/quantification of peptide related impurities revealed that the integrity of the impurity profile of the related peptide impurities obtained by the participant is crucial for the impact on accuracy of the VE mass fraction assignment. The assessment of the mass fraction of peptide impurities is based on the assumption that only the most consistent set of results is taken for the calculation of the KCRVPepImp. The sum of the combined cis/trans VE depsipeptide impurities (only identified/quantified by NRC and confirmed by BIPM and HSA) and mass fractions of peptide related impurities that have been identified by at least two participants have been used to establish the KCRVPepImp. The KCRVPepImp of 53.0 mg/g is associated with a corresponding expanded uncertainty of 17.3 mg/g (k = 2) providing a more realistic basis of evaluation for the capabilities of the participants to identify/quantify peptide related impurities. Inspection of the degree of equivalence plots for the mass fraction of peptide impurities and additional information obtained from the peptide related impurity profile indicates that in all cases the major related peptide impurity, VE depsipeptide, has not been identified. The VE depsipeptide impurity was initially and uniquely identified and quantified by the NRC by the use of 1H-NMR. The related peptide impurity mass fraction results of only four participants (NRC, LGC, LNE and HSA) are in agreement with the KCRVPepImp. The NRC has identified and quantified the VE depsipeptide whereas the LGC, LNE and HSA have not identified the VE depsipeptide but accounted for that contribution. The approach selected to obtain a KCRVVE for the mass fraction of VE is based on a mass balance calculation that takes into account the most consistent set of results for the peptide related impurities KCRVPepImp, TFA mass fraction and the water mass fraction. The KCRVVE for CCQM-K115.2018 is 613 mg/g with a corresponding expanded uncertainty of the KCRVVE of 20 mg/g (k = 2). To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database https://www.bipm.org/kcdb/. The final report has been peer-reviewed and approved for publication by the CCQM, according to the provisions of the CIPM Mutual Recognition Arrangement (CIPM MRA).

Optical conductivity [σ (ω)] of CeRhIn5 and YbNi3Ga9 have been measured at external pressures to 10 GPa and at low temperatures to 6 K. Regarding CeRhIn5, at ambient pressure the main feature in σ (ω) is a Drude peak due to free carriers. With increasing pressure, however, a characteristic midinfrared (mIR) peak rapidly develops in σ (ω), and its peak energy and width increase with pressure. These features are consistent with an increased conduction (c)- f electron hybridization at high pressure and show that pressure has tuned the electronic state of CeRhIn5 from very weakly to strongly hybridized ones. As for YbNi3Ga9, in contrast, a marked mIR peak is observed already at ambient pressure, indicating a strong c- f hybridization. At high pressures, however, the mIR peak shifts to lower energy and becomes diminished and seems to merge with the Drude component at 10 GPa. Namely, CeRhIn5 and YbNi3Ga9 exhibit some opposite tendencies in the pressure evolution of σ (ω) and electronic structure. These results are discussed in terms of the pressure evolution of c- f hybridized electronic states in Ce and Yb compounds, in particular in terms of the electron-hole symmetry often considered between Ce and Yb.

Objective To describe the range of symptoms of gastroesophageal reflux in healthy, full-term infants in the first 7 months of life. Design Cross-sectional, descriptive study. Median and percentile scores for the Infant Gastroesophageal Reflux Questionnaire–Revised (I-GERQ-R) were calculated for each of the following age groups of infants: 0 to 2, 2 to 4, 4 to 6, and 6 to 7 months. Psychometric properties, including internal consistency reliability and concurrent validity of the I-GERQ-R, were also tested. Setting Online. Participants Primary caregivers of 559 healthy, full-term (≥37 weeks gestational age) infants younger than 7 months. Measurements Participants were asked to answer questions about themselves, their family, and their infant and to complete the I-GERQ-R, the Infant Gastrointestinal Symptoms Questionnaire, and the Neonatal Eating Assessment Tool. Results Symptoms of gastroesophageal reflux decreased over the first 7 months of life. Scores in the 95th percentile decreased from 19 in infants 0 to 2 months old to 16.7 in infants 6 to 7 months old. Internal consistency reliability of the I-GERQ-R was acceptable (Cronbach’s α = .71). The I-GERQ-R had evidence of concurrent validity with the Infant Gastrointestinal Symptoms Questionnaire (rs = .69, p Conclusions Authors of prior studies used a cutoff score of 16 for the diagnosis of gastroesophageal reflux disease in infants younger than 18 months. Our results indicate that symptoms of reflux change with age over the first 7 months of life and that using more age-specific reference values may be more appropriate. Health care providers can use these age-specific percentile scores, together with clinical assessment, to identify significant symptomatology related to gastroesophageal reflux disease.

Immunogenic cell death is triggered by several cytotoxic agents inducing a release of damage-associated molecular patterns and by dying cells fostering an innate and an antigen-specific adaptive immune response. Combination strategies of immunoadjuvant chemotherapies and effective immunomodulators open new therapeutic perspectives for tumors not responding to current immunotherapies.

Proportional navigation (PN) is a well-known guidance law for a two-vehicle engagement. In the two-vehicle engagement, the miss distance (the closest distance between the two vehicles) is desired to be zero that can be achieved by annulling the line-of-sight (LOS) rate. The PN guidance law requires information of the LOS rate and, if it is available, the closing velocity (the relative approaching speed to the target). The PN guidance system may degrade the system performance due to target maneuvers. Such target maneuvers should be compensated with a guidance system. However, it is difficult to obtain accurate target information due to the target's unpredictable maneuvers, velocity changes, and so on. This paper proposes a novel guidance law based on the PN guidance law using only LOS rate information. The proposed guidance is referred to as uncertainty and disturbance-compensated intercept guidance. Potential of the proposed guidance law is demonstrated with some representative simulations. Robust performance of the proposed guidance system for a time-lag system is also shown with simulation results.

The superconducting property of Zr(1−x)Cox (x = 10–50 at.%) alloys and a Zr55Co30Al15 bulk metallic glass fabricated using techniques of rapid solidification was investigated. The Zr55Co30Al15 alloy crystallized by heat treatment in a vacuum atmosphere exhibited superconductivity of Tc,on = 2.4 K. This was attributable to the superconducting property of a crystalline Zr–Co alloy precipitated in the Zr55Co30Al15 alloy. The Tc,on of the crystalline Zr(1−x)Cox alloy was sensitive to the Co content. The increase of Co content for the Zr(1−x)Cox alloy led to the decrease of Tc,on. The Zr(1−x)Cox alloy exhibited superconductivity of a maximum Tc,on = 3.9 K for the Zr80Co20 alloy with superconducting nanocrystal particles embedded in the amorphous matrix.

The crystallization behavior of Ca 50 Mg 22.5 Cu 27.5 metallic glass in supercooled liquid has been examined using a technique of differential thermal analysis. Crystallization mechanism of the alloys during isothermal annealing in supercooled liquid was analyzed using the Johnson–Mehl–Avrami (JMA) equation. The experimental data of the isothermal crystallization was interpreted by the JMA model. The Avrami exponents for the ribbon and bulk alloys are 2.5 ± 0.5 and 2.3 ± 0.3, respectively. Both values of the Avrami exponent suggested that the crystal growth is controlled by a long-range diffusion process. The scaling law for crystallization of the alloys was also examined.

BACKGROUND AND AIM Magnifying endoscopy combined with narrow-band imaging (ME-NBI) has been used for differential diagnosis of various focal lesions. The aim of our study was to evaluate ME-NBI criteria for cancer diagnosis in superficial depressed gastric lesions in comparison to conventional white light endoscopy (WLE). PATIENTS AND METHODS ME-NBI and WLE images of 100 superficial gastric depressions (55 depressed cancers, 45 benign depressions) were independently evaluated by 11 endoscopists blinded to the diagnosis in each case. The presence or absence of predefined ME-NBI findings relating to microvasculature and fine mucosal structure (FMS) was recorded. A general diagnosis of benign or malignant also had to be given on the basis of a general assessment of features of color and shape as shown in the ME-NBI and WLE images, respectively, without regard to any prespecified criteria. RESULTS Multivariate and ROC analysis demonstrated that the triad of FMS disappearance, microvascular dilation, and heterogeneity appeared to be the best combination for diagnosis of gastric cancer. ME-NBI diagnosis with the triad attained a good specificity (85 %, theoretically calculated if all of the triad were positive), which was significantly ( P < 0.001) superior to WLE general diagnosis (65 %), and comparable with ME-NBI general diagnosis (80 %). The sensitivities of the three diagnoses (ME-NBI with the triad 69 %, WLE general diagnosis 71 %, ME-NBI general diagnosis 72 %) were comparably moderate. The kappa values (interobserver concordance) for ME-NBI diagnosis with the triad (0.47) and ME-NBI general diagnosis (0.48) were superior to the kappa value for WLE diagnosis (0.34). CONCLUSION The triad of FMS disappearance, microvascular dilation, and heterogeneity has good specificity for the diagnosis of superficial depressed gastric carcinoma, but the sensitivity needs to be improved.

TS-1 is a novel oral anticancer agent comprised of tegafur, a prodrug of 5- flurouracil, and two modulators. A phase i study of tS-1 plus carboplatin combination therapy was conducted to determine the maximum tolerated dose (MTD), recommended dose (RD), and dose limiting toxicities (DLT) in advanced non-small-cell lung cancer (NSClC). TS-1 was given orally at a dose of 80 mg/m(2)/day for 2 weeks, followed by a 2-week rest. Carboplatin was given intravenously on day 8 at a dose of 4.0, 5.0, 6.0 area under the curve (AUC) values. Fifteen patients with advanced NSClC were analyzed. the grade 3-4 toxicities observed during the first cycle were febrile neutropenia (6%), anemia (6%), anorexia (6%), and diarrhea (6%). these toxicities were reversible and manageable. The MTD for carboplatin was evaluated to be more than 6.0 AUC values, as one of six patients developed Dlt at this dose. the RD for carboplatin was estimated as 6.0 AUC values. Objective responses were seen in five patients (response rate 33%).

Background and aim: Gastric carcinogenesis involves CpG island hypermethylation (CIHM) of tumor-suppressor genes. Although the CIHM of these genes occurs in non-neoplastic gastric cells, it is unclear whether this epigenetic alteration is linked with aging and/or gastric cancer risk. We investigated this linkage in noncancerous gastric mucosa infected with H. pylori. Subjects and methods: Noncancerous corpus mucosa was endoscopically obtained from H. pylori-positive gastric cancer patients (n = 34), and age-matched H. pylori-positive noncancerous controls (n = 68). Genomic DNA retrieved from the mucosa was subjected to methylation-specific polymerase chain reaction for p16, Ecad, and DAPK genes. Linkage between CIHM and clinicopathologic factors was evaluated. Results: CIHM rates of DAPK, Ecad, and p16 promoters were significantly higher in noncancerous gastric mucosa of gastric cancer patients (91, 88, and 68%, respectively) than in noncancerous controls (71, 53, and 25%, respectively). Multivariate regression analysis showed a significant linkage between CIHM in noncancerous mucosa and coexistence of gastric cancer. Significant linkage between polymorphoneutrophil infiltration and CIHM was observed except for CIHM of p16. No linkage was observed between CIHM and other parameters, including age. High CIHM status (all three tested genes methylated) was associated with an increased risk of gastric cancer, with an odds ratio of 9.8 (95% confidence interval, 3.8–25.3). Conclusions: In a subset of the H. pylori-infected population, CIHM of tumor-suppressor genes in noncancerous gastric mucosa is linked with the risk of gastric cancer and polymorphoneutrophil infiltration, but not aging. CIHM is a potential marker of gastric cancer risk.

Quaternary Zr 47 Cu 40 Al 10 M 3 (M: IVA ∼ VIA), Zr 50 Cu 37 Al 10 M 3 (M: VIIA ∼ IB), and Zr 50 Cu 40 Al 7 M 3 (M: IIB∼) bulk glass alloys (BGAs) were examined to clarify the glassy structure of Zr 50 Cu 40 Al 10 BGA. The glass structural difference was evaluated by the volume change due to structural relaxation at the glass-transition temperature ( T g ); the volume shrinkage was estimated using density measurement. The results indicated that Pd, Ag, Pt, and Au, which are characterized by a filled d-shell electron structure, are effective for enhancing volume expansion in a glass structure. Furthermore, the volume changes in quaternary Zr–Cu–Al–M BGAs could be classified into two groups. This implies a difference in glass structure between the Zr 50 Cu 37 Al 10 M 3 (M = Pd, Ag, Pt, and Au) BGA and others examined in this study.

In order to clarify the relationship between the glass structure and mechanical properties, splat-cooled and tilt-cast Zr–Cu–Al glassy alloys were studied. The glass structure difference was estimated considering thermal factors (glass-transition temperature, crystallization temperature, etc.) and the volume change from the as-cast state to fully relaxed state. The compositional dependence of the tensile strength and Charpy-impact energy is closely related to that of the glass-transition temperature and volume change. We also examined the Poisson's ratio to find out ductile glassy alloys. As a result, solvent(Zr)-enriched off-eutectic glassy alloys show rather high Poisson's ratios.