Non-thermally trapped inflation by tachyonic dark photon production

We show that a dark Higgs field charged under U(1)$_{\rm H}$ gauge symmetry is trapped at the origin for a long time, if dark photons are produced by an axion condensate via tachyonic preheating. The trapped dark Higgs can drive late-time inflation, producing a large amount of entropy. Unlike thermal inflation, the dark Higgs potential does not have to be very flat, because the effective mass for the dark Higgs is enhanced by large field values of dark photons with extremely low momentum. After inflation, the dark Higgs decays into massive dark photons, which further decay into the SM particles through a kinetic mixing. We show that a large portion of the viable parameter space is within the future experimental searches for the dark photon, because the kinetic mixing is bounded below for successful reheating. We also comment on the Schwinger effect which can hamper the tachyonic production of dark photons, when the mass of dark photon is not the St\"{u}ckelberg mass, but is generated by the Higgs mechanism. Such non-thermal trapped inflation could be applied to other cosmological scenarios such as the early dark energy, known as one of the solutions to the Hubble tension.Comment: 11pages, 7 figures, references adde

Combined analysis of intratumoral human equilibrative nucleoside transporter 1 (hENT1) and ribonucleotide reductase regulatory subunit M1 (RRM1) expression is a powerful predictor of survival in patients with pancreatic carcinoma treated with adjuvant gem

Background. Although postoperative adjuvant chemotherapy for pancreatic carcinoma improves survival in some patients, its efficacy varies among individuals. The aim of this study was to determine the usefulness of intratumoral expression of human equilibrative nucleoside transporter 1 (hENT1) and ribonucleotide reductase regulatory subunit M1 (RRM1) as predictive markers of the efficacy of adjuvant gemcitabine-based chemotherapy for pancreatic carcinoma after operative resection. Methods. The expression of intratumoral hENT1 and RRM1 was examined immunohistochemically in 109 patients with pancreatic carcinoma who received adjuvant gemcitabine-based chemotherapy after operative resection. Relationships between clinicopathologic factors, including hENT1 and RRM1 expression, and disease-free and overall survival (DFS and OS) were evaluated by univariate and multivariate analyses. Results. The 5-year DFS and OS rates for the 109 patients were 26% and 31%, respectively. In univariate analysis, both hENT1 and RRM1 expression were significantly associated with DFS (hENT1, P = .004; RRM1, P = .011) and OS (hENT1, P = .001; RRM1, P = .040). In multivariate analysis, both were independent factors for DFS (hENT1, P = .001; RRM1, P = .009) and OS (hENT1, P = .001, RRM1, P = .019). Evaluation of the combination analysis of both was also identified as a powerful independent predictor of DFS (P < .001) and OS (P < .001). Conclusion. Expression of hENT1 and RRM1 is predictive of the efficacy of adjuvant gemcitabine-based chemotherapy for pancreatic carcinoma after operative resection. In addition, their combined analysis has greater predictive value than either factor alone. (Surgery 2013;153:565-75.)広島大学(Hiroshima University)博士(医学)Philosophy in Medical Sciencedoctora

Structure of Space-time Correlations of Bursting Phenomenon in an Open-channel Flow

The present study is to investigate the structure of space-time correlations of bursting motions, such as ejections and sweeps in an open-channel flow, by a new conditional sampling method in which simultaneous measurements of the instantaneous Reynolds stress have been performed by two dual-hot-film probes. One probe was fixed near the edge of buffer layer and used as a detecting probe of the bursting motions, while the other probe was moved in both the streamwise and flow-depth-wise directions. The main conclusions obtained from the above are as follows : (1) The spatial and time scales of the streamwise turbulent velocity component are larger than those of the vertical velocity component. (2) The spatial and time scales of the sweep motion are also larger than those of the ejection motion. (3) The spatial scale of the ejection motion extends more widely downstream than upstream, and vice versa for the sweep motion. (4) The bursting motion is a kind of a large-scale eddy structure, and its coherent structure is fairly inclined downstream toward the wall. It is convected downstream with a longer life-time than the bursting passing-period, namely in the frozen-turbulence-like manner. Next, a qualitative model is proposed which attempts to explain the space-time structures of the bursting phenomenon, on the basis of the above anemometry information and other visual information

Raphe AMPA receptors and nicotinic acetylcholine receptors mediate ketamine-induced serotonin release in the rat prefrontal cortex.

Several lines of evidence indicate that ketamine has a rapid antidepressant-like effect in rodents and humans, but underlying mechanisms are unclear. In the present study, we investigated the effect of ketamine on serotonin (5-HT) release in the rat prefrontal cortex by in vivo microdialysis. A subcutaneous administration of ketamine (5 and 25 mg/kg) significantly increased the prefrontal 5-HT level in a dose-dependent manner, which was attenuated by local injection of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) antagonists into the dorsal raphe nucleus (DRN). Direct stimulation of AMPARs in the DRN significantly increased prefrontal 5-HT level, while intra-DRN injection of ketamine (36.5 nmol) had no effect. Furthermore, intra-DRN injection of an α 4 β 2-nicotinic acetylcholine receptor (nAChR) antagonist, dihydro-β-erythroidine (10 nmol), significantly attenuated the subcutaneous ketamine-induced increase in prefrontal 5-HT levels. These results suggest that AMPARs and α 4 β 2-nAChRs in the DRN play a key role in the ketamine-induced 5-HT release in the prefrontal cortex

Evaluation of heterogeneity dose distributions for Stereotactic Radiotherapy (SRT): comparison of commercially available Monte Carlo dose calculation with other algorithms

<p>Abstract</p> <p>Background</p> <p>The purpose of this study was to compare dose distributions from three different algorithms with the x-ray Voxel Monte Carlo (XVMC) calculations, in actual computed tomography (CT) scans for use in stereotactic radiotherapy (SRT) of small lung cancers.</p> <p>Methods</p> <p>Slow CT scan of 20 patients was performed and the internal target volume (ITV) was delineated on Pinnacle³. All plans were first calculated with a scatter homogeneous mode (SHM) which is compatible with Clarkson algorithm using Pinnacle³treatment planning system (TPS). The planned dose was 48 Gy in 4 fractions. In a second step, the CT images, structures and beam data were exported to other treatment planning systems (TPSs). Collapsed cone convolution (CCC) from Pinnacle³, superposition (SP) from XiO, and XVMC from Monaco were used for recalculating. The dose distributions and the Dose Volume Histograms (DVHs) were compared with each other.</p> <p>Results</p> <p>The phantom test revealed that all algorithms could reproduce the measured data within 1% except for the SHM with inhomogeneous phantom. For the patient study, the SHM greatly overestimated the isocenter (IC) doses and the minimal dose received by 95% of the PTV (PTV95) compared to XVMC. The differences in mean doses were 2.96 Gy (6.17%) for IC and 5.02 Gy (11.18%) for PTV95. The DVH's and dose distributions with CCC and SP were in agreement with those obtained by XVMC. The average differences in IC doses between CCC and XVMC, and SP and XVMC were -1.14% (p = 0.17), and -2.67% (p = 0.0036), respectively.</p> <p>Conclusions</p> <p>Our work clearly confirms that the actual practice of relying solely on a Clarkson algorithm may be inappropriate for SRT planning. Meanwhile, CCC and SP were close to XVMC simulations and actual dose distributions obtained in lung SRT.</p

Peptidyl prolyl isomerase Pin1-inhibitory activity of d-glutamic and d-aspartic acid derivatives bearing a cyclic aliphatic amine moiety

AbstractPin1 is a peptidyl prolyl isomerase that specifically catalyzes cis–trans isomerization of phosphorylated Thr/Ser-Pro peptide bonds in substrate proteins and peptides. Pin1 is involved in many important cellular processes, including cancer progression, so it is a potential target of cancer therapy. We designed and synthesized a novel series of Pin1 inhibitors based on a glutamic acid or aspartic acid scaffold bearing an aromatic moiety to provide a hydrophobic surface and a cyclic aliphatic amine moiety with affinity for the proline-binding site of Pin1. Glutamic acid derivatives bearing cycloalkylamino and phenylthiazole groups showed potent Pin1-inhibitory activity comparable with that of known inhibitor VER-1. The results indicate that steric interaction of the cyclic alkyl amine moiety with binding site residues plays a key role in enhancing Pin1-inhibitory activity

The Role of Dorsal Raphe Serotonin Neurons in the Balance between Reward and Aversion

Background: Reward processing is fundamental for animals to survive and reproduce. Many studies have shown the importance of dorsal raphe nucleus (DRN) serotonin (5-HT) neurons in this process, but the strongly correlative link between the activity of DRN 5-HT neurons and rewarding/aversive potency is under debate. Our primary objective was to reveal this link using two different strategies to transduce DRN 5-HT neurons. Methods: For transduction of 5-HT neurons in wildtype mice, adeno-associated virus (AAV) bearing the mouse tryptophan hydroxylase 2 (TPH2) gene promoter was used. For transduction in Tph2-tTA transgenic mice, AAVs bearing the tTA-dependent TetO enhancer were used. To manipulate the activity of 5-HT neurons, optogenetic actuators (CheRiff, eArchT) were expressed by AAVs. For measurement of rewarding/aversive potency, we performed a nose-poke self-stimulation test and conditioned place preference (CPP) test. Results: We found that stimulation of DRN 5-HT neurons and their projections to the ventral tegmental area (VTA) increased the number of nose-pokes in self-stimulation test and CPP scores in both targeting methods. Concomitantly, CPP scores were decreased by inhibition of DRN 5-HT neurons and their projections to VTA. Conclusion: Our findings indicate that the activity of DRN 5-HT neurons projecting to the VTA is a key modulator of balance between reward and aversion