Continuous background produced by the graphite collimator

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Number of active transcription factor binding sites is essential for the Hes7 oscillator

BACKGROUND: It is commonly accepted that embryonic segmentation of vertebrates is regulated by a segmentation clock, which is induced by the cycling genes Hes1 and Hes7. Their products form dimers that bind to the regulatory regions and thereby repress the transcription of their own encoding genes. An increase of the half-life of Hes7 protein causes irregular somite formation. This was shown in recent experiments by Hirata et al. In the same work, numerical simulations from a delay differential equations model, originally invented by Lewis, gave additional support. For a longer half-life of the Hes7 protein, these simulations exhibited strongly damped oscillations with, after few periods, severely attenuated the amplitudes. In these simulations, the Hill coefficient, a crucial model parameter, was set to 2 indicating that Hes7 has only one binding site in its promoter. On the other hand, Bessho et al. established three regulatory elements in the promoter region. RESULTS: We show that – with the same half life – the delay system is highly sensitive to changes in the Hill coefficient. A small increase changes the qualitative behaviour of the solutions drastically. There is sustained oscillation and hence the model can no longer explain the disruption of the segmentation clock. On the other hand, the Hill coefficient is correlated with the number of active binding sites, and with the way in which dimers bind to them. In this paper, we adopt response functions in order to estimate Hill coefficients for a variable number of active binding sites. It turns out that three active transcription factor binding sites increase the Hill coefficient by at least 20% as compared to one single active site. CONCLUSION: Our findings lead to the following crucial dichotomy: either Hirata's model is correct for the Hes7 oscillator, in which case at most two binding sites are active in its promoter region; or at least three binding sites are active, in which case Hirata's delay system does not explain the experimental results. Recent experiments by Chen et al. seem to support the former hypothesis, but the discussion is still open

The transient magnetization process and operations in the plunger type electromagnet

D.C. electromagnets are generally used in electric devices such as an electromagnetic switch, an electro­magnetic relay. an electromagneticvalue, etc.. The transientmagnetizationaffects the determination of the electromagnetic force and the performance characteristic. However. there are few reports on the detailsof the transient phenomena in an electromagnet. The purpose of this paper is to describe two phe­nomena which are obtained from the numerical analyses and some experiments.One is the timelag of magnetic flux due to the skin effect. The other is the transient magnetization process near the gap in the plunger type electromagnet made of solid core

Everolimus Rescue Treatment for Chronic Rejection After Pediatric Living Donor Liver Transplantation: 2 Case Reports

Ueno T., Hiwatashi S., Saka R., et al. Everolimus Rescue Treatment for Chronic Rejection After Pediatric Living Donor Liver Transplantation: 2 Case Reports. Transplantation Proceedings 50, 2872 (2018); https://doi.org/10.1016/J.TRANSPROCEED.2018.03.079.Chronic rejection (CR) remains a challenging complication after liver transplantation. Everolimus, which is a mammalian target of rapamycin inhibitor, has an anti-fibrosis effect. We report here the effect of everolimus on CR. Case 1 was a 7-year-old girl who underwent living donor liver transplantation (LDLT) shortly after developing fulminant hepatitis at 10 months of age. Liver function tests (LFTs) did not improve after transplantation despite treatment with tacrolimus + mycophenolate mofetil (MMF). Antithymoglobulin (ATG) and steroid pulse therapy were also ineffective. The patient was diagnosed with CR, and everolimus was started with a target trough level of about 5 ng/mL. LFTs improved and pathological examination showed no progression of hepatic fibrosis. Case 2 was a 10-year-old girl with Alagille syndrome who underwent LDLT at 1 year of age. She had biopsy-proven acute cellular rejection with prolonged LFT abnormalities beginning 3 years after transplantation. She was treated with steroid pulse therapy, followed by MMF, tacrolimus, and prednisolone. Her condition did not improve, even after subsequent ATG administration. CR was suspected based on liver biopsy in the fourth postoperative year, and everolimus was introduced. The target trough level was around 5 ng/mL, but was reduced to 3 ng/mL due to stomatitis. Four years have passed since the initiation of everolimus, and LFTs are stable with no progression of liver biopsy fibrosis. We describe 2 cases in which everolimus was administered for CR. In both cases, LFTs improved and fibrosis did not progress, suggesting that everolimus is an effective treatment for CR after LDLT

Anti–USAG-1 therapy for tooth regeneration through enhanced BMP signaling

先天性無歯症に対する分子標的薬の開発 --USAG-1を標的分子とした歯再生治療--. 京都大学プレスリリース. 2021-02-15.Uterine sensitization–associated gene-1 (USAG-1) deficiency leads to enhanced bone morphogenetic protein (BMP) signaling, leading to supernumerary teeth formation. Furthermore, antibodies interfering with binding of USAG-1 to BMP, but not lipoprotein receptor–related protein 5/6 (LRP5/6), accelerate tooth development. Since USAG-1 inhibits Wnt and BMP signals, the essential factors for tooth development, via direct binding to BMP and Wnt coreceptor LRP5/6, we hypothesized that USAG-1 plays key regulatory roles in suppressing tooth development. However, the involvement of USAG-1 in various types of congenital tooth agenesis remains unknown. Here, we show that blocking USAG-1 function through USAG-1 knockout or anti–USAG-1 antibody administration relieves congenital tooth agenesis caused by various genetic abnormalities in mice. Our results demonstrate that USAG-1 controls the number of teeth by inhibiting development of potential tooth germs in wild-type or mutant mice missing teeth. Anti–USAG-1 antibody administration is, therefore, a promising approach for tooth regeneration therapy