Hydraulic Performances of a Vertical Gate to Effluxes

This paper concerns hydraulic performances of a vertical gate to free and submerged underflows in the light of the one-dimensional treatment of hydraulic analysis. For the free underflow, main emphasis is placed on the contraction of efflux influential to the stage-discharge relationship for practical uses, through a thorough research of past works added to by further experimentations by the authors. A possible scale effect in physical simulation for the present problem will be also explained. For the submerged underflow, the transition problem from free to submerged flow at the gate will be accented. Some discussions of the discharge coefficient of the gate to the submerged underflow are also made

Stochastic Tunneling of Two Mutations in a Population of Cancer Cells

Cancer initiation, progression, and the emergence of drug resistance are driven by specific genetic and/or epigenetic alterations such as point mutations, structural alterations, DNA methylation and histone modification changes. These alterations may confer advantageous, deleterious or neutral effects to mutated cells. Previous studies showed that cells harboring two particular alterations may arise in a fixed-size population even in the absence of an intermediate state in which cells harboring only the first alteration take over the population; this phenomenon is called stochastic tunneling. Here, we investigated a stochastic Moran model in which two alterations emerge in a cell population of fixed size. We developed a novel approach to comprehensively describe the evolutionary dynamics of stochastic tunneling of two mutations. We considered the scenarios of large mutation rates and various fitness values and validated the accuracy of the mathematical predictions with exact stochastic computer simulations. Our theory is applicable to situations in which two alterations are accumulated in a fixed-size population of binary dividing cells

A huge ovarian smooth muscle tumor : a case report

Ovarian smooth muscle tumors are a very rare type of ovarian tumor. In this paper, we report the case of a 62-year-old woman who had a huge smooth muscle tumor of the right ovary. The values of all the serum tumor markers were within normal limit. The tumor measured 25 cm in diameter and weighed 6,200 g. Histological examination revealed that coagulative cellular atypia was modetare to severe, necrosis was not present and mitotic index was low. According to the criteria for the evaluation of the uterine smooth muscle tumors, this huge tumor was diagnosed as atypical leiomyoma. However, we finally made a diagnosis of this tumor as a smooth muscle tumor of uncertain malignant potential (STUMP) because of its huge size. Further information is required regarding the characteristics of ovarian smooth muscle tumor and the propriety to introduce uterine tumor histological criteria to ovarian tumors

Magnetized Fast Isochoric Laser Heating for Efficient Creation of Ultra-High-Energy-Density States

The quest for the inertial confinement fusion (ICF) ignition is a grand challenge, as exemplified by extraordinary large laser facilities. Fast isochoric heating of a pre-compressed plasma core with a high-intensity short-pulse laser is an attractive and alternative approach to create ultra-high-energy-density states like those found in ICF ignition sparks. This avoids the ignition quench caused by the hot spark mixing with the surrounding cold fuel, which is the crucial problem of the currently pursued ignition scheme. High-intensity lasers efficiently produce relativistic electron beams (REB). A part of the REB kinetic energy is deposited in the core, and then the heated region becomes the hot spark to trigger the ignition. However, only a small portion of the REB collides with the core because of its large divergence. Here we have demonstrated enhanced laser-to-core energy coupling with the magnetized fast isochoric heating. The method employs a kilo-tesla-level magnetic field that is applied to the transport region from the REB generation point to the core which results in guiding the REB along the magnetic field lines to the core. 7.7 $\pm$ 1.3 % of the maximum coupling was achieved even with a relatively small radial area density core ($\rho R$ $\sim$ 0.1 g/cm$^2$). The guided REB transport was clearly visualized in a pre-compressed core by using Cu-$K_\alpha$ imaging technique. A simplified model coupled with the comprehensive diagnostics yields 6.2\% of the coupling that agrees fairly with the measured coupling. This model also reveals that an ignition-scale areal density core ($\rho R$ $\sim$ 0.4 g/cm$^2$) leads to much higher laser-to-core coupling ($>$ 15%), this is much higher than that achieved by the current scheme

Defective function of GABA-containing synaptic vesicles in mice lacking the AP-3B clathrin adaptor

AP-3 is a member of the adaptor protein (AP) complex family that regulates the vesicular transport of cargo proteins in the secretory and endocytic pathways. There are two isoforms of AP-3: the ubiquitously expressed AP-3A and the neuron-specific AP-3B. Although the physiological role of AP-3A has recently been elucidated, that of AP-3B remains unsolved. To address this question, we generated mice lacking μ3B, a subunit of AP-3B. μ3B−/− mice suffered from spontaneous epileptic seizures. Morphological abnormalities were observed at synapses in these mice. Biochemical studies demonstrated the impairment of γ-aminobutyric acid (GABA) release because of, at least in part, the reduction of vesicular GABA transporter in μ3B−/− mice. This facilitated the induction of long-term potentiation in the hippocampus and the abnormal propagation of neuronal excitability via the temporoammonic pathway. Thus, AP-3B plays a critical role in the normal formation and function of a subset of synaptic vesicles. This work adds a new aspect to the pathogenesis of epilepsy

Anti-Inflammatory Effects of Rebamipide Eyedrop Administration on Ocular Lesions in a Murine Model of Primary Sjögren’s Syndrome

Background: Topical therapy is effective for dry eye, and its prolonged effects should help in maintaining the quality of life of patients with dry eye. We previously reported that the oral administration of rebamipide (Reb), a mucosal protective agent, had a potent therapeutic effect on autoimmune lesions in a murine model of Sjögren’s syndrome (SS). However, the effects of topical treatment with Reb eyedrops on the ocular lesions in the murine model of SS are unknown. 　 　Methods and Finding: Reb eyedrops were administered to the murine model of SS aged 4–8 weeks four times daily. Inflammatory lesions of the extraorbital and intraorbital lacrimal glands and Harderian gland tissues were histologically evaluated. The direct effects of Reb on the lacrimal glands were analyzed using cultured lacrimal gland cells. Tear secretions of Reb-treated mice were significantly increased compared with those of untreated mice. In addition to the therapeutic effect of Reb treatment on keratoconjunctivitis, severe inflammatory lesions of intraorbital lacrimal gland tissues in this model of SS were resolved. The mRNA expression levels of IL-10 and mucin 5Ac in conjunctival tissues from Reb-treated mice was significantly increased compared with those of control mice. Moreover, lactoferrin production from lacrimal gland cells was restored by Reb treatment. 　Conclusion: Topical Reb administration had an anti-inflammatory effect on the ocular autoimmune lesions in the murine model of SS and a protective effect on the ocular surfaces

First Case of Cytokine Release Syndrome after Nivolumab for Gastric Cancer

Introduction: Cytokine release syndrome (CRS) is a potentially life-threatening systemic disease that has been observed after treatment with antibodies and adoptive T cell therapies. In this case, we observed nivolumab-induced CRS in a patient with gastric cancer. Case Presentation: A 43-year-old male with advanced gastric cancer was treated with nivolumab as a third-line chemotherapy. He had no history of allergies. Eight days after the first administration of nivolumab, fever, tachycardia, appetite loss and increases in liver and biliary enzymes were observed. Computed tomography revealed neither bile duct obstruction nor progression of liver metastases but showed that there was edema of the Gleason sheath. Histopathological analysis of the liver revealed cholestatic liver injury with CD8+ T lymphocyte and macrophage infiltration. Neither viral infection nor autoimmune disease was revealed. His symptoms were similar to those of CRS observed after T cell therapy. We diagnosed his disease as nivolumab-induced liver injury and cholangitis accompanied by CRS based on his serum cytokine levels. Discussion/Conclusion: To the best of our knowledge, this is the first report of nivolumab-induced CRS in a patient with gastric cancer