Signal recognition particle binds to translating ribosomes before emergence of a signal anchor sequence.

The bacterial signal recognition particle (SRP) is part of the machinery that targets ribosomes synthesizing membrane proteins to membrane-embedded translocons co-translationally. Recognition of nascent membrane proteins occurs by virtue of a hydrophobic signal-anchor sequence (SAS) contained in the nascent chain, usually at the N terminus. Here we use fluorescence-based stopped-flow to monitor SRP-ribosome interactions with actively translating ribosomes while an SRP substrate is synthesized and emerges from the peptide exit tunnel. The kinetic analysis reveals that, at cellular concentrations of ribosomes and SRP, SRP rapidly binds to translating ribosomes prior to the emergence of an SAS and forms an initial complex that rapidly rearranges to a more stable engaged complex. When the growing peptide reaches a length of ∼50 amino acids and the SAS is partially exposed, SRP undergoes another conformational change which further stabilizes the complex and initiates targeting of the translating ribosome to the translocon. These results provide a reconciled view on the timing of high-affinity targeting complex formation, while emphasizing the existence of preceding SRP recruitment steps under conditions of ongoing translation

Traditioneel bestuur in Uganda: Een Afrikaanse Renaissance

Het is 9 januari 1998 en de airbus van Sabena raakt de vruchtbare grond van Uganda. Ik heb mijzelf vanuit Nederland gelanceerd naar Uganda, gelegen in het politiek onstabiele Grote Meren gebied van Oost Afrika, om daar onderzoek te doen naar de rol van traditionele leiders in de huidige Afrikaanse staat

Cost of porcine reproductive and respiratory syndrome virus at individual farm level – An economic disease model

Porcine reproductive and respiratory syndrome (PRRS) is reported to be among the diseases with the highest economic impact in modern pig production worldwide. Yet, the economic impact of the disease at farm level is not well understood as, especially in endemically infected pig herds, losses are often not obvious. It is therefore difficult for farmers and veterinarians to appraise whether control measures such as virus elimination or vaccination will be economically beneficial for their farm. Thus, aim of this study was to develop an epidemiological and economic model to determine the costs of PRRS for an individual pig farm. In a production model that simulates farm outputs, depending on farm type, farrowing rhythm or length of suckling period, an epidemiological model was integrated. In this, the impact of PRRS infection on health and productivity was estimated. Financial losses were calculated in a gross margin analysis and a partial budget analysis based on the changes in health and production parameters assumed for different PRRS disease severities. Data on the effects of endemic infection on reproductive performance, morbidity and mortality, daily weight gain, feed efficiency and treatment costs were obtained from literature and expert opinion. Nine different disease scenarios were calculated, in which a farrow-to-finish farm (1000 sows) was slightly, moderately or severely affected by PRRS, based on changes in health and production parameters, and either in breeding, in nursery and fattening or in all three stages together. Annual losses ranged from a median of € 75′724 (90% confidence interval (C.I.): € 78′885–€ 122′946), if the farm was slightly affected in nursery and fattening, to a median of € 650′090 (90% C.I. € 603′585–€ 698′379), if the farm was severely affected in all stages. Overall losses were slightly higher if breeding was affected than if nursery and fattening were affected. In a herd moderately affected in all stages, median losses in breeding were € 46′021 and € 422′387 in fattening, whereas costs were € 25′435 lower in nursery, compared with a PRRSV-negative farm. The model is a valuable decision-support tool for farmers and veterinarians if a farm is proven to be affected by PRRS (confirmed by laboratory diagnosis). The output can help to understand the need for interventions in case of significant impact on the profitability of their enterprise. The model can support veterinarians in their communication to farmers in cases where costly disease control measures are justified

Synergism of microwaves and ultrasound for advanced biorefineries

AbstractConventional energy sources are limited and non-renewable and their consumption contributes to greenhouse gas emissions. The world is in need of advanced biorefineries to meet ever growing energy demands associated with population growth and economic development. An advanced biorefinery should use renewable and sustainable (both in quality and quantity) feedstock that gives rise to higher energy gains with minimum non-renewable energy and resource consumption. Development of advanced biorefineries is currently encircled by two major issues. The first issue is to ensure adequate biofuel feedstock supplies while the second issue is to develop resource-efficient technologies for the feedstock conversion to maximize energy and economic and environmental benefits. While microalgae, microbial derived oils, and agricultural biomass and other energy crops show great potential for meeting current energy demands in a sustainable manner, process intensification and associated synergism can improve the resource utilization efficiency. Synergism of process intensification tools is important to increase energy efficiency, reduce chemical utilization and associated environmental impacts, and finally process economics. Among the many process intensification methods, this commentary provides a perspective on the essential role of MWs and US and their synergy in biofuel production. Individual, sequential, and simultaneous applications of MWs and US irradiations can be utilized for process intensification of various biofuels production and selective recovery of high value bioproducts. Process related barriers, namely mass and heat transfer limitations, can be eliminated by this synergism while improving the reaction efficiency and overall process economics significantly. In this article, a brief review focused on recent developments in MW and US mediated process intensification for biofuel synthesis and associated issues in their synergism followed by a discussion on current challenges and future prospective is presented

Eslicarbazepine acetate as monotherapy in clinical practice: Outcomes from Euro-Esli

OBJECTIVES: To assess the effectiveness and safety/tolerability of eslicarbazepine acetate (ESL) monotherapy in clinical practice in Europe. MATERIALS AND METHODS: Euro-Esli was a pooled analysis of 14 European clinical practice studies. Responder rate (≥50% seizure frequency reduction) and seizure freedom rate (seizure freedom at least since prior visit) were assessed after 3, 6 and 12 months of ESL treatment and at last visit. Adverse events (AEs) and AEs leading to ESL discontinuation were assessed throughout follow-up. A subanalysis was conducted to assess outcomes for patients treated initially with ESL monotherapy and for patients treated at the last visit with ESL monotherapy. RESULTS: ESL was used as monotherapy in 88/2045 (4.3%) patients initially and in 229/1340 (17.1%) patients at the last visit. At 12 months, responder and seizure freedom rates were 94.1% and 88.2%, respectively, in patients treated initially with ESL monotherapy, and 93.2% and 77.4%, respectively, in patients treated at the last visit with ESL monotherapy. Corresponding values for patients treated initially with ESL adjunctive therapy were 74.8% and 39.0%, respectively; and for patients treated at the last visit with ESL adjunctive therapy, corresponding values were 70.4% and 25.9%, respectively. Safety and tolerability were generally comparable in patients treated with ESL as monotherapy or adjunctive therapy. The most commonly reported AEs (≥5% of patients in any group) were dizziness, somnolence, instability/ataxia, and fatigue. CONCLUSIONS: These clinical practice data support the use of ESL as monotherapy, as well as adjunctive therapy, for focal-onset seizures, complementing evidence from clinical trials.info:eu-repo/semantics/publishedVersio

Hypofractionated or Conventionally Fractionated Adjuvant Radiotherapy After Regional Lymph Node Dissection for High-Risk Stage III Melanoma

Aims: Adjuvant radiotherapy can be beneficial after regional lymph node dissection for high-risk stage III melanoma, as it has been shown to reduce the risk of recurrence in the node field. However, the optimal fractionation schedule is unknown and both hypofractionated and conventionally fractionated adjuvant radiotherapy are used. The present study examined the oncological outcomes of these two approaches in patients treated in an era before effective systemic immunotherapy became available. Materials and methods: This retrospective cohort study involved 335 patients with stage III melanoma who received adjuvant radiotherapy after therapeutic regional lymph node dissection for metastatic melanoma between 1990 and 2011. Information on tumour characteristics, radiotherapy doses and fractionation schedules and patient outcomes was retrieved from the institution's database and patients' medical records. Results: Hypofractionated radiotherapy (median dose 33 Gy in six fractions over 3 weeks) was given to 95 patients (28%) and conventionally fractionated radiotherapy (median dose 48 Gy in 20 fractions over 4 weeks) to 240 patients (72%). Five-year lymph node field control rates were 86.0% (95% confidence interval 78.4–94.4%) for the hypofractionated group and 85.5% (95% confidence interval 80.5–90.7%) for the conventional fractionation group (P = 0.87). There were no significant differences in recurrence-free survival (RFS) (41.7%, 95% confidence interval 32.5–53.5 versus 31.9%, 95% confidence interval 26.1–38.9; P = 0.18) or overall survival (41.2%, 95% confidence interval 32.1–52.8 versus 45.0%, 95% confidence interval 38.7–52.4; P = 0.77). On multivariate analysis, extranodal spread was associated with decreased RFS (P = 0.04) and the number of resected lymph nodes containing metastatic melanoma was associated with decreased RFS (P = 0.0006) and overall survival (P = 0.01). Conclusion: Lymph node field control rates, RFS and overall survival were similar after hypofractionated and conventionally fractionated adjuvant radiotherapy. The presence of extranodal spread and an increasing number of positive lymph nodes were predictive of an unfavourable outcome

Lekker: rot of vers? de fruitvlieg als fijnproever, een statistische analyse

Onderzoekers willen weten hoe ze fruitvliegen het beste kunnen kweken. Hierbij spelen voedselkwaliteit voor de volwassen fruitvlieg en diens nageslacht een belangrijke rol. De gemiddelde burger wil juist weten hoe hij de vliegjes zo ver mogelijk weghoudt of zo snel mogelijk kwijtraakt. Voor beide groepen is het belangrijk om te weten hoe fruitvliegjes hun voedselbron en broedsubstraat (waar ze hun eitjes leggen) kiezen. In dit experiment, waarvan de proefopzet beschreven wordt, kan worden bepaald tot welk rottingsstadium van de appel fruitvliegen zich het meest aangetrokken voele

Flexible Power Modeling of LTE Base Stations

With the explosion of wireless communications in number of users and data rates, the reduction of network power consumption becomes more and more critical. This is especially true for base stations which represent a dominant share of the total power in cellular networks. In order to study power reduction techniques, a convenient power model is required, providing estimates of the power consumption in different scenarios. This paper proposes such a model, accurate but simple to use. It evaluates the base station power consumption for different types of cells supporting the 3GPP LTE standard. It is flexible enough to enable comparisons between state-of-the-art and advanced configurations, and an easy adaptation to various scenarios. The model is based on a combination of base station components and sub-components as well as power scaling rules as functions of the main system parameters