Tuberous Sclerosis Complex 1 Regulates dE2F1 Expression during Development and Cooperates with RBF1 to Control Proliferation and Survival

Previous studies in Drosophila melanogaster have demonstrated that many tumor suppressor pathways impinge on Rb/E2F to regulate proliferation and survival. Here, we report that Tuberous Sclerosis Complex 1 (TSC1), a well-established tumor suppressor that regulates cell size, is an important regulator of dE2F1 during development. In eye imaginal discs, the loss of tsc1 cooperates with rbf1 mutations to promote ectopic S-phase and cell death. This cooperative effect between tsc1 and rbf1 mutations can be explained, at least in part, by the observation that TSC1 post-transcriptionally regulates dE2F1 expression. Clonal analysis revealed that the protein level of dE2F1 is increased in tsc1 or tsc2 mutant cells and conversely decreased in rheb or dTor mutant cells. Interestingly, while s6k mutations have no effect on dE2F1 expression in the wild-type background, S6k is absolutely required for the increase of dE2F1 expression in tsc2 mutant cells. The canonical TSC/Rheb/Tor/S6k pathway is also an important determinant of dE2F1-dependent cell death, since rheb or s6k mutations suppress the developmentally regulated cell death observed in rbf1 mutant eye discs. Our results provide evidence to suggest that dE2F1 is an important cell cycle regulator that translates the growth-promoting signal downstream of the TSC/Rheb/Tor/S6k pathway

Supreme Court Rulings on Determining the Cartel End Date

Since the very nature of cartels is to operate in ways that are undisclosed and difficult to track, it is often a matter of heated dispute in courts as to when a cartel has ended or been abandoned. Moreover, the cartel duration is a critical issue because it affects not only the level of sanctions imposed, but also the damages amount sought against the cartelists. The Korean Supreme Court has issued several important rulings regarding this matter, but there still remain areas where further guidance and clarification would be beneficial. Thus, this article explores the relevant Korean Supreme Court rulings and concludes that it is time for the highest court to further articulate the legal test for determining the ending date of a cartel in an effort to eliminate legal uncertainty and establish clearer guidance for market participants

Experimental Verification of Overlimiting Current by Surface Conduction and Electro-Osmotic Flow in Microchannels

Direct evidence is provided for the transition from surface conduction (SC) to electro-osmotic flow (EOF) above a critical channel depth (d) of a nanofluidic device. The dependence of the overlimiting conductance (OLC) on d is consistent with theoretical predictions, scaling as d[superscript −1] for SC and d[superscript 4 over 5] for EOF with a minimum around d=8  μm. The propagation of transient deionization shocks is also visualized, revealing complex patterns of EOF vortices and unstable convection with increasing d. This unified picture of surface-driven OLC can guide further advances in electrokinetic theory, as well as engineering applications of ion concentration polarization in microfluidics and porous media.Basic Science Research Program (Grant 2013R1A1A1008125)Global Frontier Project (Center for Integrated Smart Sensor. Grant CISS-2011-0031870)Future Based Technology Development Program (Nano Fields) (Grant 2012-0001033)Korea. Ministry of Health and Welfare (Grant HI13C1468)Korea. Ministry of Health and Welfare (Grant HI14C0559)Korea (South). Ministry of Science, ICT and Future Planning (Korean Health Technology RND Project

Fabrication of n-type nanotube transistors with large-work-function electrodes

The authors found experimentally that carbon nanotube field-effect transistors (CNFETs) could exhibit n -type characteristics even though their electrodes consist of a large-work-function metal such as Co. To explain their result, which is contrary to the general belief that CNFETs with large-work-function electrodes always lead to p -type characteristics, ab initio electronic structure calculation for the metal-carbon nanotube junction was performed, which showed that the Fermi level alignment at the junction could sensitively depend on microscopic structures of the metal-carbon nanotube junction. This suggests that deposition method of electrodes as well as the metal type could be utilized to obtain n -type CNFETs.open121

Surgical Treatment of Inferior Vena Cava Invasion in Patients with Renal Pelvis Transitional Cell Carcinoma by Use of Human Cadaveric Aorta

We herein report a case of radical nephroureterectomy and replacement of the inferior vena cava (IVC) with ahuman cadaveric aortic graft for a patient with renal pelvis transitional cell carcinoma associated with IVC infiltration. In advanced disease, radical surgery is essential to achieve long-term survival. This case entails the use of another treatment option among the numerous options currently available for the management of patients with advanced renal cancer associated with IVC invasion

E2F and p53 Induce Apoptosis Independently during Drosophila Development but Intersect in the Context of DNA Damage

In mammalian cells, RB/E2F and p53 are intimately connected, and crosstalk between these pathways is critical for the induction of cell cycle arrest or cell death in response to cellular stresses. Here we have investigated the genetic interactions between RBF/E2F and p53 pathways during Drosophila development. Unexpectedly, we find that the pro-apoptotic activities of E2F and p53 are independent of one another when examined in the context of Drosophila development: apoptosis induced by the deregulation of dE2F1, or by the overexpression of dE2F1, is unaffected by the elimination of dp53; conversely, dp53-induced phenotypes are unaffected by the elimination of dE2F activity. However, dE2F and dp53 converge in the context of a DNA damage response. Both dE2F1/dDP and dp53 are required for DNA damage-induced cell death, and the analysis of rbf1 mutant eye discs indicates that dE2F1/dDP and dp53 cooperatively promote cell death in irradiated discs. In this context, the further deregulation in the expression of pro-apoptotic genes generates an additional sensitivity to apoptosis that requires both dE2F/dDP and dp53 activity. This sensitivity differs from DNA damage-induced apoptosis in wild-type discs (and from dE2F/dDP-induced apoptosis in un-irradiated rbf1 mutant eye discs) by being dependent on both hid and reaper. These results show that pro-apoptotic activities of dE2F1 and dp53 are surprisingly separable: dp53 is required for dE2F-dependent apoptosis in the response to DNA damage, but it is not required for dE2F-dependent apoptosis caused simply by the inactivation of rbf1

Prognostic Factors Affecting Surgical Outcomes in Squamous Cell Carcinoma of External Auditory Canal

Objectives Carcinomas of the external auditory canal (EAC) are rare, and management remains challenging. Previous studies seeking prognostic factors for EAC cancers included cancers other than carcinomas. In this study, we analyzed the treatment outcomes of, prognostic factors for, and survival rates associated with specifically squamous cell carcinoma (SCC) of the EAC. Methods A retrospective review of 26 consecutive patients diagnosed with SCCs of the EAC in a 10-year period was performed in terms of clinical presentation, stage, choice of surgical procedure, and adjunct therapy. Overall survival (OS) and recurrence-free survival (RFS) were calculated and univariate analysis of prognostic factors was performed. Results The median age of the 26 patients with SCCs of the EAC was 63 years (range, 40 to 72 years), and 16 males and 10 females were included. According to the modified University of Pittsburgh staging system, the T stages were T1 in 11, T2 in six, T3 in four, and T4 in five cases. The surgical procedures employed were wide excision in three cases, lateral temporal bone resection (LTBR) in 17, and extended LTBR in four, and subtotal temporal bone resection in two. Two patients underwent neoadjuvant chemotherapy, and two underwent adjuvant chemotherapy. One patient received preoperative radiation therapy, and eleven received postoperative radiation therapy. Of the possibly prognostic factors examined, advanced preoperative T stage and advanced overall stage were significant predictors of RFS, but not of OS. Conclusion The advanced T stage and overall stage were associated with decreased survival after surgical treatment in patients with SCC of the EAC, highlighting the importance of clinical vigilance and early detection

Implantable Cardioverter-Defibrillator Lead Extraction by Conventional Traction and Counter-Traction Technique

A 46-year-old man presented to our institution with inappropriate implantable cardioverter-defibrillator (ICD) shock delivery. The ICD (single chamber, dual shock coils) was implanted for sustained monomorphic ventricular tachycardia with unstable hemodynamics and underlying systolic left ventricular dysfunction. ICD interrogation revealed recurrent episodes of ICD shock due to noise sensing and increased impedance of right ventricular (RV)-lead. With the impression of lead fracture, ICD lead extraction was performed. The fractured ICD lead was completely removed by traction of locking stylet and counter-traction of polypropylene dilator sheath. A new lead was inserted and the patient was discharged without complications after 2 days. To our knowledge, this is the first report on ICD lead extraction by conventional traction and counter-traction technique in Korea