Grapiprant is an analgesic and anti‐inflammatory drug in the piprant class that was approved in March 2016 by FDA's Center for Veterinary Medicine for the control of pain and inflammation associated ...with osteoarthritis (OA) in dogs. Grapiprant functions as a selective antagonist of the EP4 receptor, one of the four prostaglandin E2 (PGE2) receptor subtypes. The EP4 receptor mediates PGE2‐elicited nociception, and grapiprant has been shown to decrease pain in several rat inflammatory pain models. It was also effective in reducing pain associated with OA in humans, providing evidence for its mechanism of action in these species. The estimated canine efficacy dose of between 1.3 and 1.7 mg/kg, p.o. with a methylcellulose suspension, once a day, was predicted based on calculations from comparative affinity of grapiprant to the dog, rat, and human EP4 receptors, serum protein binding, effective doses defined in rat models of pain and inflammation, and human clinical studies. The results of this study guided the doses to be tested in the pilot study and demonstrated the usefulness of the efficacy dose prediction method. The approved commercial tablet dose of grapiprant is 2 mg/kg once a day for the control of pain and inflammation associated with OA in dogs.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Maintaining oral function in older individuals with missing teeth is important for leading a healthy and independent life. This study aimed to evaluate whether simple isometric exercises can maintain ...and improve the oral function maximum occlusal force (MOF) and masticatory ability (MA) and the masticatory muscle properties masseter muscle thickness (MMT) and echo intensity (MMEI) in older adults during the maintenance phase of removable prosthetic treatment. Participants were randomly categorized into the intervention and control groups. The mouthpieces were distributed, and participants were instructed to use them for exercising. The intervention group was instructed to perform maximum clenching for 10 s, whereas the control group was instructed to tap the teeth at an arbitrary speed for 10 s. Both were repeated five times at an interval of 5 s between each activity and twice daily for 4 weeks. The outcomes were measured after a month of exercise. The intervention group showed a significant improvement in the MOF, MMT during contraction, MMT at rest and MMEI during contraction. There were no significant differences in the MA and MMEI at rest. In the control group, no improvement was observed in any of the parameters. When the isometric exercises were performed using a mouthpiece, there was an improvement in the oral function and masseter muscle properties in older individuals with Eichner B status who used dentures.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
The travertine deposits could provide a prospective geomicrobiological snapshot of the early Earth considering its similarity with ancient stromatolites. Herein, we investigated the travertine ...carbonate deposits in a calcareous and sulfidic hot spring at Sipoholon, Northern Sumatra, Indonesia, with an emphasis on the formation of a laminated texture similar to one observed in the stromatolites. The travertine deposits were associated with microbial mats of different colors that change from yellow, pink, and green, lowering water temperature and H2S concentration along the water passages. A phylotype analysis of the Prokaryotic 16S rRNA gene revealed that chemolithoautotrophic sulfur and hydrogen oxidizing bacteria were abundant in the yellow sediment around vent sites. At the same time, photoheterotrophs, a linage of Anaerolineae, dominated the pink to green sediment at mid- to downstream. Laminated textures are developed in pink and green-colored sediments among these categories. Monitoring water chemical parameters and sediment texture for an Anaerolineae-dominated sample collected from a midstream site revealed that daily lamination was formed due to the daytime biofilm formation under the stable chemical composition of water conditions except for dissolved oxygen concentration. Daily laminations were also formed in other samples by microbial communities with lower Anaerolineae abundance. Further, the results showed that if mineral precipitation and microbial growth rates are appropriately balanced, cyanobacteria were not essential for the lamina development. This indicating that such a geochemical system could occur in early-time stromatolites even before the evolution of cyanobacteria. The microbial-mineral precipitation systems identified in this study provide significant insights into the formation of stromatolites, which can in turn shed light on the history of early Earth.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
For shrimp immune defences, prophenoloxidase (proPO) activating system and antimicrobial peptides in circulating haemocytes play important roles. In the present study, the effects of ...lipopolysaccharide (LPS) injection on gene expression of penaeidins, crustin, serine proteinase and proPO in haemocytes were determined using real-time reverse transcription–polymerase chain reaction (PCR) in the Pacific white shrimp
Litopenaeus vannamei. After injection of LPS, mRNA levels of antimicrobial peptides, penaeidin 2 (PEN2), penaeidin 3 (PEN3), penaeidin 4 (PEN4) and crustin decreased in a dose-dependent manner, while mRNA levels of serine proteinase and proPO did not change significantly. In a time-course experiment, injection of LPS caused significant depression in mRNA levels of PEN2, PEN3, PEN4 and crustin at 4
h post-injection, and the depressed mRNA levels returned to initial levels by 72
h post-injection. On the other hand, mRNA levels of serine proteinase and proPO did not show a significant change after injection. These results suggest that the antimicrobial peptide system responds to LPS injection at a gene expression level while the proPO system does not respond at a gene expression level.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Although branch duct intraductal papillary-mucinous neoplasms (IPMNs) of the pancreas without mural nodules are frequently observed in asymptomatic subjects, the natural history of these lesions has ...never been studied. The aim of this study was to elucidate the natural history of branch duct IPMNs without mural nodules.
Eighty-two patients who had no apparent mural nodules on initial examination were selected for follow-up. All subjects underwent examinations by imaging modalities including endoscopic retrograde pancreatography, and were followed-up by regular examinations once or twice a year. Serial changes of the maximum cystic diameter and the appearance of mural nodules were studied during the observation periods ranging from 14 to 148 months (median, 61 months).
Nine (11.0%) of 82 patients exhibited obvious progression of cystic dilatation (median, 59 months). Of these nine patients with cystic enlargement, six continued with regular follow-up examinations. Three cases underwent surgical resection, and were pathologically diagnosed as adenoma in two and borderline in one. Four patients (4.9%) showed newly developed mural nodules in dilated branch ducts (median, 105 months). Histological analysis revealed three cases classified as adenoma and one as carcinoma in situ. None of the remaining 69 patients (84.1%) showed any changes in dilated branch ducts (median, 57 months).
Most branch duct IPMNs without mural nodules remained unchanged during long-term follow-up. Although follow-up with careful examination is required to detect newly developed mural nodules in dilated branch ducts, branch duct IPMNs without mural nodules can be followed-up without surgery.
Optimal filtering is the crucial technique for the data analysis of transition-edge-sensor (TES) calorimeters to achieve their state-of-the-art energy resolutions. Filtering out the ‘bad’ data from ...the dataset is important because it otherwise leads to the degradation of energy resolutions, while it is not a trivial task. We propose a neural network-based technique for the automatic goodness tagging of TES pulses, which is fast and automatic and does not require bad data for training.
Since 1995, more than 500 exoplanets have been detected using different techniques, of which 12 were detected with gravitational microlensing. Most of these are gravitationally bound to their host ...stars. There is some evidence of free-floating planetary-mass objects in young star-forming regions, but these objects are limited to massive objects of 3 to 15 Jupiter masses with large uncertainties in photometric mass estimates and their abundance. Here, we report the discovery of a population of unbound or distant Jupiter-mass objects, which are almost twice (1.8(+1.7)(-0.8)) as common as main-sequence stars, based on two years of gravitational microlensing survey observations towards the Galactic Bulge. These planetary-mass objects have no host stars that can be detected within about ten astronomical units by gravitational microlensing. However, a comparison with constraints from direct imaging suggests that most of these planetary-mass objects are not bound to any host star. An abrupt change in the mass function at about one Jupiter mass favours the idea that their formation process is different from that of stars and brown dwarfs. They may have formed in proto-planetary disks and subsequently scattered into unbound or very distant orbits.
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DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
To identify predictive molecular markers for gemcitabine resistance, we investigated changes in the expression of four genes associated with gemcitabine transport and metabolism during the ...development of acquired gemcitabine resistance of pancreatic cancer cell lines. The expression levels of human equilibrative nucleoside transporter-1 (hENT1), deoxycytidine kinase (dCK), RRM1, and RRM2 mRNA were analysed by real-time light cycler-PCR in various subclones during the development of acquired resistance to gemcitabine. Real-time light cycler-PCR demonstrated that the expression levels of either RRM1 or RRM2 progressively increased during the development of gemcitabine resistance. Expression of dCK was slightly increased in cells resistant to lower concentrations of gemcitabine, but was decreased below the undetectable level in higher concentration-resistant subclones. Expression of hENT1 was increased in the development of gemcitabine resistance. As acquired resistance to gemcitabine seems to correlate with the balance of these four factors, we calculated the ratio of hENT1 x dCK/RRM1 x RRM2 gene expression in gemcitabine-resistant subclones. The ratio of gene expression decreased progressively with development of acquired resistance in gemcitabine-resistant subclones. Furthermore, the expression ratio significantly correlated with gemcitabine sensitivity in eight pancreatic cancer cell lines, whereas no single gene expression level correlated with the sensitivity. These results suggest that the sensitivity of pancreatic cancer cells to gemcitabine is determined by the ratio of four factors involved in gemcitabine transport and metabolism. The ratio of the four gene expression levels correlates with acquired gemcitabine-resistance in pancreatic cancer cells, and may be useful as a predictive marker for the efficacy of gemcitabine therapy in pancreatic cancer patients.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, SIK, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Absolute grand total cross section for electron scattering from CO
2
is obtained in the energy range from 20 eV down to 9 meV with a very narrow electron energy width of 11 meV using the ...threshold-photoelectron source employing synchrotron radiation. Although the obtained grand total cross section shows the general features of the cross-section behavior known for the low-energy electron scattering from CO
2
, namely the marked rise below 2 eV and the resonance enhancement at about 4 eV, several new features were revealed, especially at the
2
Π
u
resonance. The energy position for the maxima of the grand total cross section at the
2
Π
u
resonance appeared to be lower than that has been known. Also found are clear oscillatory structures resolved on the broad enhancement of the grand total cross section at around the
2
Π
u
resonance. The present measurement also revealed a threshold feature due to the vibrational excitation of asymmetric stretch mode in the grand total cross section. The vibrational excitation cross section for asymmetric stretch mode at the threshold is estimated from the feature.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, SIK, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
OBJECTIVES
The standard surgical treatment for patients with non-small-cell lung cancer (NSCLC) is lobectomy with systematic nodal dissection (SND). Lobe-specific patterns of nodal metastases have ...been recognized, and lobe-specific SND (L-SND) has been reported. We performed L-SND depending on patient-related factors, such as age or the presence of diabetes or respiratory dysfunction, or in the context of specific tumour-related factors, such as the presence of a tumour with a wide area of ground-glass opacity.
METHODS
Between September 2002 and December 2008, 335 consecutive patients with clinical and intraoperative N0 NSCLC underwent curative lobectomies at Shizuoka Cancer Center Hospital. Among these 335 patients, 206 underwent SND (Group A) and 129 underwent L-SND. Of the 129 patients undergoing L-SND, 98 underwent L-SND due to patient-related factors (Group B) and 31 underwent L-SND due to tumour-related factors (Group C).
RESULTS
There were no significant differences in morbidity or blood loss between patients undergoing SND or L-SND, but there was a significant difference in the mean operative times. The 5-year disease-free survival (5-DFS) and 5-year overall survival (5-OS) of patients in Group C were 100%. Although the patients in Group B showed no significant difference in 5-DFS and 5-OS compared with Group A, patients in Group B had significantly more initial recurrence of mediastinal node cancer than did the Group A patients (P = 0.0050).
CONCLUSIONS
The recurrence of mediastinal node cancer in patients undergoing L-SND was significantly greater than that in those undergoing SND.
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