Mangan-superoksid-dismutaza (MnSOD) katalizuje NO-zavisno nitrovanje ostatka tirozina

The peroxynitrite-induced nitration of manganese superoxide dismutase (MnSOD) tyrosine residue, which causes enzyme inactivation, is well established, This led to suggestions that MnSOD nitration and inactivation in vivo, detected in various diseases associated with oxidative stress and overproduction of nitric monoxide (NO), conditions which favor peroxynitrite formation, is also caused by peroxynitrite. However, our previous ill vitro study demonstrated that exposure of MnSOD to NO led to NO conversion into nitrosonium (NO+) and nitroxyl (NO-) species, which caused enzyme modifications and inactivation. Here it is reported that MnSOD is tyrosine nitrated upon exposure to NO, as well as that MnSOD nitration contributes to inactivation of the enzyme. Collectively, these observations provide a compelling argument supporting the generation of nitrating species in MnSOD exposed to NO and shed a new light on MnSOD tyrosine nitration and inactivation ill vivo. This may represent a novel mechanism by which MnSOD protects cell from deleterious effects associated with overproduction of NO. However, extensive MnSOD modification and inactivation associated with prolonged exposure to NO will amplify the toxic effects caused by increased cell superoxide and NO levels.Dobro je poznato da peroksinitrit izaziva nitrovanje ostataka tirozina u mangan-superoksid- dismutazi (MnSOD) što dovodi do inaktivacije enzima. Pokazano je da nitrovanje i inaktivacija MnSOD-a nastaje u raznim bolestima za koje je karakteristič an oksidativni stres i povećana produkcija azot-monoksida (NO). Pošto se pri ovim uslovima očekuje nastajanje peroksinitrita predloženo je da peroksinitrit izaziva nitrovanje i inaktivaciju MnSOD in vivo. U našem prethodnom radu pokazali smo da MnSOD katalizuje transformaciju NO u nitrozonijum (NO+) i nitroksil (NO–) reaktivne vrste, te identifikovali neke od modifikacija molekula enzima koje pri tome nastaju izazivajući njegovu inaktivaciju. U ovom radu je pokazano da pri izlaganju MnSOD azot-monoksidu dolazi i do nitrovanja ostatka tirozina u molekulu enzima, što doprinosi njegovoj inaktivaciji. Ovi rezultati ukazuju da pri interakciji MnSOD sa NO dolazi do nastajanja nitrujućih vrsta, što baca novo svetlo na proces nitrovanja ostataka tirozina i inaktivaciju MnSOD in vivo. Ovo može da predstavlja novi mehanizam kojim MnSOD štiti ćeliju odštetnih efekata izazvanih hiperprodukcijom azot-monoksida. Međutim ekstenzivne modifikacije i inaktivacija MnSOD do kojih dolazi pri produženom izlaganju enzima NO, uvećaće toksične efekte izazvane povećanim koncentracijama superoksida i NO u ćeliji

Absorbed Dose Uncertainty Estimation for Proton Therapy

Successful radiotherapy treatment depends on the absorbed dose evaluation and the possibility to define metrological characteristics of the therapy beam. Radiotherapy requires tumor dose delivery with expanded uncertainty less than +/- 5 %. It is particularly important to reduce uncertainty during therapy beam calibration as well as to apply all necessary ionization chamber correction factors. Absorbed dose to water was determined using ionometric method. Calibration was performed in reference cobalt beam. Combined standard uncertainty of the calculated absorbed dose to water in 65 MeV proton beam was +/- 1.97% while the obtained expanded uncertainty of absorbed dose for the same beam quality was +/- 5.02%. The uncertainty estimation method has been developed within the project TESLA

Autonomous electrical current monitoring system for aircraft

Aircraft monitoring systems offer enhanced safety, reliability, reduced maintenance cost and improved overall flight efficiency. Advancements in wireless sensor networks (WSN) are enabling unprecedented data acquisition functionalities, but their applicability is restricted by power limitations, as batteries require replacement or recharging and wired power adds weight and detracts from the benefits of wireless technology. In this paper, an energy autonomous WSN is presented for monitoring the structural current in aircraft structures. A hybrid inductive/hall sensing concept is introduced demonstrating 0.5 A resolution, < 2% accuracy and frequency independence, for a 5 A – 100 A RMS, DC-800 Hz current and frequency range, with 35 mW active power consumption. An inductive energy harvesting power supply with magnetic flux funnelling, reactance compensation and supercapacitor storage is demonstrated to provide 0.16 mW of continuous power from the 65 μT RMS field of a 20 A RMS, 360 Hz structural current. A low-power sensor node platform with a custom multi-mode duty cycling network protocol is developed, offering cold starting network association and data acquisition/transmission functionality at 50 μW and 70 μW average power respectively. WSN level operation for 1 minute for every 8 minutes of energy harvesting is demonstrated. The proposed system offers a unique energy autonomous WSN platform for aircraft monitoring

Application of homotopy-perturbation method to fractional IVPs

Fractional initial-value problems (fIVPs) arise from many fields of physics and play a very important role in various branches of science and engineering. Finding accurate and efficient methods for solving fIVPs has become an active research undertaking. In this paper, both linear and nonlinear fIVPs are considered. Exact and/or approximate analytical solutions of the fIVPs are obtained by the analytic homotopy-perturbation method (HPM). The results of applying this procedure to the studied cases show the high accuracy, simplicity and efficiency of the approach

Scheduling Analysis of Imprecise Mixed-Criticality Real-Time Tasks

In this paper, we study the scheduling problem of the imprecise mixed-criticality model (IMC) under earliest deadline first with virtual deadline (EDF-VD) scheduling upon uniprocessor systems. Two schedulability tests are presented. The first test is a concise utilization-based test which can be applied to the implicit deadline IMC task set. The suboptimality of the proposed utilization-based test is evaluated via a widely-used scheduling metric, speedup factors. The second test is a more effective test but with higher complexity which is based on the concept of demand bound function (DBF). The proposed DBF-based test is more generic and can apply to constrained deadline IMC task set. Moreover, in order to address the high time cost of the existing deadline tuning algorithm, we propose a novel algorithm which significantly improve the efficiency of the deadline tuning procedure. Experimental results show the effectiveness of our proposed schedulability tests, confirm the theoretical suboptimality results with respect to speedup factor, and demonstrate the efficiency of our proposed algorithm over the existing deadline tunning algorithm. In addition, issues related to the implementation of the IMC model under EDF-VD are discussed.Computer Systems, Imagery and Medi

Monte Carlo Calculation of the Energy Response Characteristics of a RadFET Radiation Detector

The Metal -Oxide Semiconductor Field-Effect-Transistor (MOSFET, RadFET) is frequently used as a sensor of ionizing radiation in nuclear-medicine, diagnostic-radiology, radiotherapy quality-assurance and in the nuclear and space industries. We focused our investigations on calculating the energy response of a p-type RadFET to low-energy photons in range from 12 keV to 2 MeV and on understanding the influence of uncertainties in the composition and geometry of the device in calculating the energy response function. All results were normalized to unit air kerma incident on the RadFET for incident photon energy of 1.1 MeV. The calculations of the energy response characteristics of a RadFET radiation detector were performed via Monte Carlo simulations using the MCNPX code and for a limited number of incident photon energies the FOTELP code was also used for the sake of comparison. The geometry of the RadFET was modeled as a simple stack of appropriate materials. Our goal was to obtain results with statistical uncertainties better than 1% (fulfilled in MCNPX calculations for all incident energies which resulted in simulations with 1 - 2x10(9) histories.13th IMEKO TC1-TC7 Joint Symposium Without Measurement No Science, Without Science No Measurement, Sep 01-03, 2010, City Univ London, London, Englan

Uticaj letnjeg i zimskog perioda ishrane na telesnu razvijenost krava simentalske rase

The paper analyzed linear type traits and influence of summer and winter nutrition on body development of Simmental cattle. Test cows (paternal a half-sisters) were located in identical breedingconditions on the eastern slopes of Mount Kopaonik.Considering that expression of the genetic potential depends on the environment in which the organisms exist, the differences between summer and winter period feeding of Simmental cattle were not statistically significant (Tukey's test, p> 0.05) for the investigated properties of linear type traits and body development.U radu su analizirane linearne ocene tipa i uticaj letnjeg i zimskog perioda ishrane na telesnu razvijenost krava simentalske rase. Ispitivane krave (polusestre po ocu) nalazile su se u identičnim uslovima gajenja na istočnim padinama planine Kopaonik. S obzirom da ispoljavanje genetskog potencijala zavisi i od uslova sredine u kojoj egzistiraju organizmi, razlike između letnjeg i zimskog perioda ishrane krava simentalske rase su statistički nesignifikantne (Tukey test,p> 0.05) za ispitivana svojstva linearne ocene tipa i telesne razvijenosti

Neurological Disorders and Publication Abstracts Follow Elements of Social Network Patterns when Indexed Using Ontology Tree-Based Key Term Search

Disorders of the Central Nervous System (CNS) are worldwide causes of morbidity and mortality. In order to further investigate the nature of the CNS research, we generate from an initial reference a controlled vocabulary of CNS disorder-related terms and ontological tree structure for this vocabulary, and then apply the vocabulary in an analysis of the past ten years of abstracts (N = 10,488) from a major neuroscience journal. Using literal search methodology with our terminology tree, we find over 5,200 relationships between abstracts and clinical diagnostic topics. After generating a network graph of these document-topic relationships, we find that this network graph contains characteristics of document-author and other human social networks, including evidence of scale-free and power law-like node distributions. However, we also found qualitative evidence for Z-normal-type (albeit logarithmically skewed) distributions within disorder popularity. Lastly, we discuss potential consumer-centered as well as clinic-centered uses for our ontology and search methodology

Text mining of adverse events in clinical trials: Deep learning approach

Background: Pharmacovigilance and safety reporting, which involves processes for monitoring the use of medicines in clinical trials, plays a critical role in the identification of previously unrecognized adverse events or changes in the patterns of adverse events. Objective: This study aimed to demonstrate feasibility of automating the coding of adverse events described in the narrative section of the serious adverse event report forms to enable a statistical analysis of the aforementioned patterns. Methods: We used the Unified Medical Language System (UMLS) as the coding scheme, which integrates 217 source vocabularies, thus enabling coding against other relevant terminologies such as ICD-10, MedDRA and SNOMED. We used MetaMap, highly configurable dictionary lookup software, to identify mentions of the UMLS concepts. We trained a binary classifier using Bidirectional Encoder Representations from Transformer (BERT), a transformer-based language model that captures contextual relationships, to differentiate between mentions of the UMLS concepts that represent adverse events and those that do not. Results: The model achieved a high F1 score of 0.8080 despite the class imbalance. This is 10.15 percent points lower than human-like performance, but also 17.45 percent points higher than the baseline approach. Conclusions: These results confirmed that automated coding of adverse events described in the narrative section of the serious adverse event reports is feasible. Once coded, adverse events can be statistically analyzed so that any correlations with the trialed medicines can be estimated in a timely fashion. Keywords: natural language processing; deep learning; machine learning; classificatio

Management of perioperative bleeding risk in patients on antithrombotic medications undergoing cardiac surgery—a systematic review

Background: Antithrombotic drugs increase the risk of bleeding, especially in patients who need urgent surgery without an adequate wash-out period. This review aims to evaluate perioperative bleeding complications in patients on dual antiplatelet therapy (DAPT) or direct-acting oral anticoagulants (DOACs) undergoing high-bleeding risk cardiovascular surgery and to present currently available potential solutions to mitigate antithrombotic therapy-related bleeding complications. Methods: As a first step, we searched for relevant articles, over the last 10 years, in Medline (PubMed) and abstracted clinical information based on pre-defined criteria for bleeding complications. In the next step, an additional search evaluating potential solutions to mitigate bleeding complications was performed. The literature screening and selection process followed the principles derived from the PRISMA statement. Results: From all reviewed studies, a total of 19 articles could be included evaluating the risk for bleeding in cardiac surgery related to DAPT or DOACs and 10 papers evaluating antithrombotic drug reversal or removal in the setting of cardiovascular surgery. Reported bleeding rates ranged between 18% and 41%. The variability of the reported data is remarkable. Idarucizumab is reported to provide optimal perioperative hemostasis in up to 93% of patients. It has been observed that andexanet alfa causes unresponsiveness to the anticoagulant effects of heparin. Antithrombotic removal by intraoperative hemoadsorption is found to be associated with a significant decrease in re-thoracotomy rate, overall procedure duration, administered transfusion volumes, chest-tube drainage, and length of hospitalization. Discussion: Bleeding complications in patients treated with DAPT or DOACs in cardiac surgery are high. New costly reversal agents are available but have not been sufficiently tested in the cardio-surgical setting so far. Interestingly, bleeding-related complications seem to be effectively reduced by applying innovative intraoperative hemoadsorption techniques. Expected results from the ongoing trials should provide better insights concerning the efficacy and safety of several potential solutions. Currently, the variability of reports and the deficit of high-quality studies in this specific setting represent the major limitation for the unbiased conclusion of this review