Differential regulation of RNF8-mediated Lys48- and Lys63-based poly-ubiquitylation

Pairing of a given E3 ubiquitin ligase with different E2s allows synthesis of ubiquitin conjugates of different topologies. While this phenomenon contributes to functional diversity, it remains largely unknown how a single E3 ubiquitin ligase recognizes multiple E2s, and whether identical structural requirements determine their respective interactions. The E3 ubiquitin ligase RNF8 that plays a critically important role in transducing DNA damage signals, interacts with E2s UBCH8 and UBC13, and catalyzes both K48- and K63-linked ubiquitin chains. Interestingly, we report here that a single-point mutation (I405A) on the RNF8 polypeptide uncouples its ability in catalyzing K48- and K63-linked ubiquitin chain formation. Accordingly, while RNF8 interacted with E2s UBCH8 and UBC13, its I405A mutation selectively disrupted its functional interaction with UBCH8, and impaired K48-based poly-ubiquitylation reactions. In contrast, RNF8 I405A preserved its interaction with UBC13, synthesized K63-linked ubiquitin chains, and assembled BRCA1 and 53BP1 at sites of DNA breaks. Together, our data suggest that RNF8 regulates K48- and K63-linked poly-ubiquitylation via differential RING-dependent interactions with its E2s UBCH8 and UBC13, respectively.published_or_final_versio

Implementing guidelines for the prescribing of vancomycin and teicoplanin

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Perioperative celecoxib administration for pain management after total knee arthroplasty – A randomized, controlled study

<p>Abstract</p> <p>Background</p> <p>Non-steroidal anti-inflammatory drugs (NSAIDs) are recommended for multimodal postoperative pain management. We evaluated opioid-sparing effects and rehabilitative results after perioperative celecoxib administration for total knee arthroplasty.</p> <p>Methods</p> <p>This was a prospective, randomized, observer-blind control study. Eighty patients that underwent total knee arthroplasty were randomized into two groups of 40 each. The study group received a single 400 mg dose of celecoxib, one hour before surgery, and 200 mg of celecoxib every 12 hours for five days, along with patient-controlled analgesic (PCA) morphine. The control group received only PCA morphine for postoperative pain management. Visual analog scale (VAS) pain scores, active range of motion (ROM), total opioid use and postoperative nausea/vomiting were analyzed.</p> <p>Results</p> <p>Groups were comparable for age, pre-operative ROM, operation duration and intraoperative blood loss. Resting VAS pain scores improved significantly in the celecoxib group, compared with controls, at 48 hrs (2.13 ± 1.68 vs. 3.43 ± 1.50, p = 0.03) and 72 hrs (1.78 ± 1.66 vs. 3.17 ± 2.01, p = 0.02) after surgery. Active ROM also increased significantly in the patients that received celecoxib, especially in the first 72 hrs [40.8° ± 17.3° vs. 25.8° ± 11.5°, p = 0.01 (day 1); 60.7° ± 18.1° vs. 45.0° ± 17.3°, p = 0.004 (day 2); 77.7° ± 15.1° vs. 64.3° ± 16.9°, p = 0.004 (day 3)]. Opioid requirements decreased about 40% (p = 0.03) in the celecoxib group. Although patients suffering from post-operative nausea/vomiting decreased from 43% in control group to 28% in celecoxib group, this was not significant (p = 0.57). There were no differences in blood loss (intra- and postoperative) between the groups. Celecoxib resulted in no significant increase in the need for blood transfusions.</p> <p>Conclusion</p> <p>Perioperative celecoxib significantly improved postoperative resting pain scores at 48 and 72 hrs, opioid consumption, and active ROM in the first three days after total knee arthroplasty, without increasing the risks of bleeding.</p> <p>Trial registration</p> <p>Clinicaltrials.gov NCT00598234</p

Cooper pairing near charged black holes

We show that a quartic contact interaction between charged fermions can lead to Cooper pairing and a superconducting instability in the background of a charged asymptotically Anti-de Sitter black hole. For a massless fermion we obtain the zero mode analytically and compute the dependence of the critical temperature T_c on the charge of the fermion. The instability we find occurs at charges above a critical value, where the fermion dispersion relation near the Fermi surface is linear. The critical temperature goes to zero as the marginal Fermi liquid is approached, together with the density of states at the Fermi surface. Besides the charge, the critical temperature is controlled by a four point function of a fermionic operator in the dual strongly coupled field theory.Comment: 1+33 pages, 4 figure

Experimental validation of fuel cell, battery and supercapacitor energy conversion system for electric vehicle applications

Due to the increasing air pollution and growing demand for green energy, the most of research is focused on renewable and sustainable energy. In this work, the PEM fuel cell is proposed as a solution to reduce the impact of the internal combustion engines on air pollution. In this paper a PEM fuel cell, battery and supercapacitor energy conversion system is proposed to ensure the energy demand for an electric vehicle is achieved. The storage system consisting of a battery and supercapacitor offers good performance in terms of autonomy and power availability. In this paper, an energy management of the PEM fuel cell electric vehicle has been first simulated in Matlab/Simulink environment and the results are discussed. Second, a Realtime experimental set up is used to test the performance of the proposed PEM fuel cell electric vehicle system. Experimental results have shown that the proposed system is able to satisfy the energy demand of the electric vehicle.N/

Shear Modes, Criticality and Extremal Black Holes

We consider a (2+1)-dimensional field theory, assumed to be holographically dual to the extremal Reissner-Nordstrom AdS(4) black hole background, and calculate the retarded correlators of charge (vector) current and energy-momentum (tensor) operators at finite momentum and frequency. We show that, similar to what was observed previously for the correlators of scalar and spinor operators, these correlators exhibit emergent scaling behavior at low frequency. We numerically compute the electromagnetic and gravitational quasinormal frequencies (in the shear channel) of the extremal Reissner-Nordstrom AdS(4) black hole corresponding to the spectrum of poles in the retarded correlators. The picture that emerges is quite simple: there is a branch cut along the negative imaginary frequency axis, and a series of isolated poles corresponding to damped excitations. All of these poles are always in the lower half complex frequency plane, indicating stability. We show that this analytic structure can be understood as the proper limit of finite temperature results as T is taken to zero holding the chemical potential fixed.Comment: 28 pages, 7 figures, added reference

Stent implantation for a totally occluded right coronary artery in a six-year-old boy after Kawasaki disease: a case report

<p>Abstract</p> <p>Introduction</p> <p>Coronary stenting has previously been considered to be less feasible in children under 12 years old due to the limitation of vascular access. We report the case of a six-year-old boy who successfully underwent stent implantation for his totally occluded right coronary artery.</p> <p>Case presentation</p> <p>A Taiwanese boy aged six years and nine months old was found to have giant aneurysms after an acute episode of Kawasaki disease. An angiography revealed that his middle right coronary artery was totally occluded. A 0.014-inch guidewire was advanced to cross the totally occluded site. After pre-dilating the middle portion of his right coronary artery with a 1.5 mm balloon, stenting of his right coronary artery was accomplished using a 2.5 × 28 mm and a 2.5 × 18 mm bare metal stent. A final angiography demonstrated no residual stenosis or dissection.</p> <p>Conclusion</p> <p>Coronary stenting could be a therapeutic option for children as young as six years old. Close follow-up is mandatory because the long-term outcome is still unclear, especially in a small child.</p

Evaluations of Tactics for Automated Negotiations

[[abstract]]Automated negotiation under the infrastructure of e-commerce is becoming an important issue. However, although the communication protocols and frameworks of automated negotiation have been extensively investigated, the corresponding tactics and strategies are still underdeveloped and need to be evaluated further. Based on the negotiation model proposed by Faratin et al., this paper examines the performance of automated negotiation tactics and intends to provide concise suggestions for the users of automated negotiation. First, theoretical analysis is used to evaluate the behavior-dependent tactics. Constructive conclusions are obtained when single-issue negotiations are considered. Next, a new framework for applying single-issue tactics to multi-issue negotiation is proposed. Based on this framework, theoretical analysis is then extended to multi-issue cases. Finally, different from the previous work, exhaustive simulations based on two-issue negotiations are performed to evaluate the effectiveness of behavior-dependent and time-dependent tactics. The experimental results provide several important insights into negotiation tactics.[[booktype]]紙本[[booktype]]電子

Role of Soil, Crop Debris, and a Plant Pathogen in Salmonella enterica Contamination of Tomato Plants

Background: In the U.S., tomatoes have become the most implicated vehicle for produce-associated Salmonellosis with 12 outbreaks since 1998. Although unconfirmed, trace backs suggest pre-harvest contamination with Salmonella enterica. Routes of tomato crop contamination by S. enterica in the absence of direct artificial inoculation have not been investigated. Methodology/Principal Findings: This work examined the role of contaminated soil, the potential for crop debris to act as inoculum from one crop to the next, and any interaction between the seedbourne plant pathogen Xanthomonas campestris pv. vesicatoria and S. enterica on tomato plants. Our results show S. enterica can survive for up to six weeks in fallow soil with the ability to contaminate tomato plants. We found S. enterica can contaminate a subsequent crop via crop debris; however a fallow period between crop incorporation and subsequent seeding can affect contamination patterns. Throughout these studies, populations of S. enterica declined over time and there was no bacterial growth in either the phyllosphere or rhizoplane. The presence of X. campestris pv. vesicatoria on co-colonized tomato plants had no effect on the incidence of S. enterica tomato phyllosphere contamination. However, growth of S. enterica in the tomato phyllosphere occurred on co-colonized plants in the absence of plant disease. Conclusions/Significance: S. enterica contaminated soil can lead to contamination of the tomato phyllosphere. A six week lag period between soil contamination and tomato seeding did not deter subsequent crop contamination. In the absence o