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Aim: Crohn's anal fistula (CAF) is a complex condition, with no agreement on which patient characteristics should be routinely reported in studies. The aim of this study was to develop a core descriptor set of key patient characteristics for reporting in all CAF research.Method: Candidate descriptors were generated from published literature and stakeholder suggestions. Colorectal surgeons, gastroenterologists and specialist nurses in inflammatory bowel disease took part in three rounds of an international modified Delphi process using nine-point Likert scales to rank the importance of descriptors. Feedback was provided between rounds to allow refinement of the next ratings. Patterns in descriptor voting were assessed using principal component analysis (PCA). Resulting PCA groups were used to organize items in rounds two and three. Consensus descriptors were submitted to a patient panel for feedback. Items meeting predetermined thresholds were included in the final set and ratified at the consensus meeting.Results: One hundred and thirty three respondents from 22 countries completed round one, of whom 67.0% completed round three. Ninety seven descriptors were rated across three rounds in 11 PCA-based groups. Forty descriptors were shortlisted. The consensus meeting ratified a core descriptor set of 37 descriptors within six domains: fistula anatomy, current disease activity and phenotype, risk factors, medical interventions for CAF, surgical interventions for CAF, and patient symptoms and impact on quality of life.Conclusion: The core descriptor set proposed for all future CAF research reflects characteristics important to gastroenterologists and surgeons. This might aid transparent reporting in future studies.

No abstract available.

Cities are monitored by sparsely positioned high-cost reference stations that fail to capture local variations. Although these stations must be ubiquitous to achieve high spatio-temporal resolutions, the required capital expenditure makes that infeasible. Here, low-cost IoT devices come into prominence; however, non-disposable and often non-rechargeable batteries they have pose a huge risk for the environment. The projected numbers of required IoT devices will also yield to heavy network traffic, thereby crippling the RF spectrum. To tackle these problems and ensure a more sustainable IoT, the cities must be monitored with fewer devices extracting highly granular data in a self-sufficient manner. Hence, this paper introduces a network architecture with energy harvesting low-cost mobile sensors mounted on bikes and unmanned aerial vehicles, underpinned by key enabling technologies. Based on the experience gained through real-world trials, a detailed overview of the technical challenges encountered when using low-cost sensors and the requirements for achieving high spatio-temporal resolutions in the 3D space are highlighted. Finally, to show the capability of the envisioned architecture in distributed sensing, a case study on air quality monitoring investigating the variations in particulate and gaseous pollutant dispersion during the first lockdown of COVID-19 pandemic is presented. The results showed that using mobile sensors is as accurate as using stationary ones with the potential of reducing device numbers, leading to a more sustainable IoT.

For developing human-centred trustworthy autonomous systems and ensuring their safe and effective integration with the society, it is crucial to enrich autonomous agents with the capacity to represent and reason about their accountability. This is, on one hand, about their accountability as collaborative teams and, on the other hand, their individual degree of accountability in a team. In this context, accountability is understood as being responsible for failing to deliver a task that a team was allocated and able to fulfil. To that end, the semantic (strategic reasoning) machinery of the Alternating-time Temporal Logic (ATL) is a natural modelling approach as it captures the temporal, strategic, and coalitional dynamics of the notion of accountability. This allows focusing on the main problem on: “Who is accountable for an unfulfilled task in multiagent teams: when, why, and to what extent?” We apply ATL-based semantics to define accountability in multiagent teams and develop a fair and computationally feasible procedure for ascribing a degree of accountability to involved agents in accountable teams. Our main results are on decidability, fairness properties, and computational complexity of the presented accountability ascription methods in multiagent teams.

Background In the randomised phase III KEYNOTE-062 study, pembrolizumab was non-inferior to chemotherapy for overall survival in patients with programmed death-ligand 1 (PD-L1)-positive [combined positive score (CPS) ≥1] advanced gastric/gastroesophageal junction (GEJ) cancer. We present findings of prespecified health-related quality-of-life (HRQOL) analyses for pembrolizumab versus chemotherapy in this population. Materials and methods HRQOL, a secondary endpoint, was measured in patients who received ≥1 dose of study treatment and completed ≥1 HRQOL questionnaire [European Organisation for the Research and Treatment of Cancer (EORTC) 30-question quality-of-life (QLQ-C30), EORTC 22-question quality-of-life gastric-cancer-specific module (QLQ-STO22)]. Least squares mean (LSM) change (baseline to week 18) in global health status/quality of life (GHS/QOL; EORTC QLQ-C30) and time to deterioration (TTD) in GHS/QOL, nausea/vomiting and appetite loss scores (EORTC QLQ-C30) and abdominal pain/discomfort scores (EORTC QLQ-STO22) were evaluated. Results The HRQOL population comprised 495 patients with CPS ≥1 (pembrolizumab, 252; chemotherapy, 243). Compliance rates at week 18 were similar for pembrolizumab and chemotherapy (EORTC QLQ-C30, 87.9% and 81.9%; EORTC QLQ-STO22, 87.9% and 81.3%, respectively). There was no between-arm difference in LSM score change in GHS/QOL [−0.16; 95% confidence interval (CI) −5.01 to 4.69; P = 0.948]. The LSM score change for most subscales showed comparable worsening in both arms. TTD for GHS/QOL [hazard ratio (HR), 0.96; 95% CI, 0.67-1.38; P = 0.826], appetite loss (HR, 0.83; 95% CI, 0.58-1.20; P = 0.314) and pain (HR, 1.22; 95% CI, 0.78-1.91; P = 0.381) were similar between arms. Longer TTD was observed for pembrolizumab versus chemotherapy for nausea/vomiting (HR, 0.61; 95% CI, 0.44-0.85; P = 0.003). Conclusions HRQOL was maintained with first-line treatment with pembrolizumab in patients with PD-L1–positive advanced gastric/GEJ cancer and was similar between pembrolizumab and chemotherapy in this population., Highlights • HRQOL was similar between pembrolizumab and chemotherapy in patients with PD-L1-positive advanced gastric/GEJ cancer. • General HRQOL as measured by QLQ-C30 GHS/QOL scores was comparable between treatment arms from baseline to week 18. • The EQ-5D-3L visual analogue scale was also equivalent between arms from baseline to week 18.

Aim: Low anterior resection syndrome (LARS) is pragmatically defined as disordered bowel function after rectal resection leading to a detriment in quality of life. This broad characterization does not allow for precise estimates of prevalence. The LARS score was designed as a simple tool for clinical evaluation of LARS. Although the LARS score has good clinical utility, it may not capture all important aspects that patients may experience. The aim of this collaboration was to develop an international consensus definition of LARS that encompasses all aspects of the condition and is informed by all stakeholders. Method: This international patient–provider initiative used an online Delphi survey, regional patient consultation meetings, and an international consensus meeting. Three expert groups participated: patients, surgeons and other health professionals from five regions (Australasia, Denmark, Spain, Great Britain and Ireland, and North America) and in three languages (English, Spanish, and Danish). The primary outcome measured was the priorities for the definition of LARS. Results: Three hundred twenty-five participants (156 patients) registered. The response rates for successive rounds of the Delphi survey were 86%, 96% and 99%. Eighteen priorities emerged from the Delphi survey. Patient consultation and consensus meetings refined these priorities to eight symptoms and eight consequences that capture essential aspects of the syndrome. Sampling bias may have been present, in particular, in the patient panel because social media was used extensively in recruitment. There was also dominance of the surgical panel at the final consensus meeting despite attempts to mitigate this. Conclusion: This is the first definition of LARS developed with direct input from a large international patient panel. The involvement of patients in all phases has ensured that the definition presented encompasses the vital aspects of the patient experience of LARS. The novel separation of symptoms and consequences may enable greater sensitivity to detect changes in LARS over time and with intervention.

Fragestellung: Um der schwerwiegenden Komplikation einer periprothetischen Infektion vorzubeugen, macht die zunehmende Anzahl multiresistenter Keime vor allem die Entwicklung präventiver Maßnahmen erforderlich. In der vorliegenden Studie wurde die knöcherne Integration einer neuen Beschichtung[zum vollständigen Text gelangen Sie über die oben angegebene URL], Deutscher Kongress für Orthopädie und Unfallchirurgie (DKOU 2019)

MicroRNAs (miRs) are important posttranscriptional regulators of gene expression. Besides their well‐characterized inhibitory effects on mRNA stability and translation, miRs can also activate gene expression. In this study, we identified a novel noncanonical function of miR‐574‐5p. We found that miR‐574‐5p acts as an RNA decoy to CUG RNA‐binding protein 1 (CUGBP1) and antagonizes its function. MiR‐574‐5p induces microsomal prostaglandin E synthase‐1 (mPGES‐1) expression by preventing CUGBP1 binding to its 3'UTR, leading to an enhanced alternative splicing and generation of an mPGES‐1 3'UTR isoform, increased mPGES‐1 protein expression, PGE2 formation, and tumor growth in vivo. miR‐574‐5p-induced tumor growth in mice could be completely inhibited with the mPGES‐1 inhibitor OIL Moreover, miR‐574‐5p is induced by IL‐1v and is strongly overexpressed in human nonsmall cell lung cancer where high mPGES‐1 expression correlates with a low survival rate. The discovered function of miR‐574‐5p as a CUGBP1 decoy opens up new therapeutic opportunities. It might serve as a stratification marker to select lung tumor patients who respond to the pharmacological inhibition of PGE2 formation.

The success of crowdsourcing projects relies critically on motivating the crowd to contribute. One particularly effective method for incentivising participants to perform tasks is to run contests. However, there are numerous ways to implement such contests in specific projects (that vary in how performance is evaluated, how to reward, and the sizes of the prizes). Additionally, with a given financial budget and a time limit, choosing incentives that maximise the total outcome (e.g., the total number of completed tasks) is not trivial, as their effectiveness in a specific project is usually unknown in advance. Therefore, we introduce algorithms to select such incentives effectively using budgeted multi-armed bandits. To do that, we first introduce the incentive selection problem, then formalise it as a 2d-budgeted multi-armed bandit, where each arm corresponds to an incentive (i.e., a contest with a specific structure). We then propose the HAIS and Stepped e-first algorithms to solve the incentive selection problem. The two algorithms are shown to be effective on simulations with synthetic data. Stepped e-first performs well, but requires a situation-specific parameter to be tuned appropriately (which may be difficult in settings with little prior experience). In contrast to this, HAIS performs better in most cases without depending significantly on the parameter tuning.

Knowing the long-term frequency of high magnitude storm events that cause coastal inundation is critical for present coastal management, especially in the context of rising sea levels and potentially increasing frequency and severity of storm events. Coastal sand dunes may provide a sedimentary archive of past storm events from which long-term frequencies of large storms can be reconstructed. This study uses novel portable optically stimulated luminescence (POSL) profiles from coastal dunes to reconstruct the sedimentary archive of storm and surge activity for Norfolk, UK. Application of POSL profiling with supporting luminescence ages and particle size analysis to coastal dunes provides not only information of dunefield evolution but also on past coastal storms. In this study, seven storm events, two major, were identified from the dune archive spanning the last 140 years. These appear to correspond to historical reports of major storm surges. Dunes appear to be only recording (at least at the sampling resolution used here) the highest storm levels that were associated with significant flooding. As such the approach seems to hold promise to obtain a better understanding of the frequency of large storms by extending the dune archive records further back to times when documentation of storm surges was sparse.

Patients with organic brain disease often present with psychiatric symptoms that closely mimic functional mental illness. This has major implications in Third-World countries where the psychiatric effects of physical disease are particularly widespread. Developing countries lack the advanced radiological investigations and other diagnostic facilities that may help to differentiate between functional and physical complaints. The association between electro-encephalographic (EEG) abnormalities and organic brain disease is well established; the benefit and importance of the EEG in ThirdWorld psychiatry is described.

We consider the problem of selecting the most influential members within a social network, in order to disseminate a message as widely as possible. This problem, also referred to as seed selection for influence maximization, has been under intensive investigation since the emergence of social networks. Nonetheless, a large body of existing research is based on the assumption that the network is completely known, whereas little work considers partially observable networks. Yet, due to many issues including the extremely large size of current networks and privacy considerations, assuming full knowledge of the network is rather unrealistic. Despite this, an influencer often wishes to distribute its message far beyond the boundaries of the known network. In this preliminary study, we propose a set of novel heuristic algorithms that specifically target nodes at this boundary, in order to maximize influence across the whole network. We show that these algorithms outperform the state of the art by up to 38% in networks with partial observability.

Head and neck squamous cell carcinoma (HNSCC) derive from the mucosa of the aerodigestive area and still have worse prognoses. Despite of new treatment strategies like the epithelial growth factor receptor (EGFR) antibody Erbitux the survival rates have not increased yet. The native mucosa expresses several receptor tyrosine kinases (RTKs) like EGFR and fibroblast growth factor receptors (FGFRs) that regulate survival and proliferation. We hypnotized that the tumor cells can switch between the different RTKs to overcome the therapy. To improve therapy in HNSCC, this study determined the effectiveness of a combined treatment targeting EGFR and FGFR. In an in-vitro drug trial Detroit-562, CAL-27 and PJ-15 cell lines were studied. BGJ398 (Novartis) that inhibits FGFRs and/or Erbitux (Merck) treatment was performed. Apoptosis was verified by caspases activity. The expression of the different RTKs was determined by immunocytochemistry and flow cytometry. The cell lines expressed EGFR, KGFR and low amounts of FGFR1 and FGFR3. In all tested cell lines, the treatment with BGJ398 or Erbitux significantly reduce survival and proliferation. The combination of both drugs enhanced the effect at lower concentrations compared to the single drug treatment. This study demonstrated that the combination of BGJ-398 and Erbitux is a promising treatment regime for HNSCCs. In the future, the reduction in drug concentrations may reduce side effects. Supported by: Novartis Pharma GmbH Der Erstautor gibt keinen Interessenkonflikt an., GMS Current Posters in Otorhinolaryngology - Head and Neck Surgery; 13:Doc229

The aim of the MoreGrasp project is to develop a noninvasive, multimodal user interface including a brain-computer interface (BCI) for intuitive control of a grasp neuroprosthesis to support individuals with high spinal cord injury (SCI) in everyday activities. We describe the current state of the project, including the EEG system, preliminary results of natural movements decoding in people with SCI, the new electrode concept for the grasp neuroprosthesis, the shared control architecture behind the system and the implementation of a user-centered design.

The introduction (§§1-33) to Hegel’s Philosophy of Right is the key to the work’s structure, its argumentative strategy and it functions as a foundation for Hegel’s practical philosophy in general. Its explanatory potential is best realised by situating it within the systematic context of the Encyclopedia of Philosophical Sciences and the Science of Logic. This interpretative strategy reveals that for Hegel, the true site of agency is ‘the concept’ and that particular individuals and their arbitrary activity are at best the concept’s ‘appearance’. This does not render their activity ‘false’ but describes how willing and freedom are ‘for us’ as self-conscious subjects that confront an external world. For Hegel, ‘true’ freedom in the sense of ‘self-determination to itself’ resides with the universal and singular concept that negatively unites itself with its objectivity to form what he calls the ‘Idea of the will’ or ‘right’.This interpretation contradicts the mainstream of contemporary Hegel scholarship since its proponents either deny the reality of the universal concept as agent or absolutely differentiate between the concept’s activity (subjective action) and its objective reality (norms, institutions). This prevents the interpreter from appreciating that it is Hegel’s concept that is manifest in form of particular willing subjects and their socio-political context. Since most commentators associate ‘activity’ or ‘freedom’ primarily with particular subjects, their notions of freedom are, by Hegel’s standards, either empty and fail to describe actual willing or they fall short of the standard of ‘true freedom’, viz. ‘self-determination to itself’ because their agents’ freedom depends on something that differs from the agents.1 The present commentary argues that such a dilemma can be avoided by an interpretation that attributes agency to Hegel’s concept. By determining itself to be Idea, the universal concept determines itself (as subject) to itself (as object) and rational agency and rational institutions are grasped as aspects of the same entity. This is what Hegel calls the unconditioned Idea of right or ‘objective freedom’.

Rank aggregation is the problem of generating an overall ranking from a set of individual votes. The aim in doing so is to produce a ranking which is as close as possible to the (unknown) correct ranking for a given distance measure such as the Kendall-tau distance. The challenge is that votes are often both noisy and incomplete. Existing work has largely focused on finding the most likely ranking for a particular noise model (such as Mallows'). Instead, here we focus on minimising the error, i.e., the expected distance between the aggregated ranking and the true underlying one. Specifically, we show that the two objectives result in different rankings, and that these differences become especially significant when many votes are missing. Furthermore, we show how to compute local improvements on existing rankings to reduce the expected error. Finally, we run extensive experiments on both synthetic and real data to compare different aggregation rules. In particular, a surprising result is that for votes generated according to the Mallows' model, Copeland often outperforms Kemeny optimal, despite the latter being the maximum likelihood estimator.

This paper presents the results of a multidisciplinary project that has revealed the location, extent\ud and character of the winter camp of the Viking Great Army at Torksey, Lincolnshire, of AD 872–3.\ud The camp lay within a naturally defended area of higher ground, partially surrounded by marshes\ud and bordered by the River Trent on its western side. It is considerably larger than the Viking camp of\ud 873–4 previously excavated at Repton, Derbyshire, and lacks the earthwork defences identified\ud there. Several thousand individuals overwintered in the camp, including warriors, craftworkers and\ud merchants. An exceptionally large and rich metalwork assemblage was deposited during the Great\ud Army’s overwintering, and metal processing and trading was undertaken. There is no evidence for a\ud pre-existing Anglo-Saxon trading site here; the site appears to have been chosen for its strategic\ud location and its access to resources. In the wake of the overwintering, Torksey developed as an\ud important Anglo-Saxon borough with a major wheel-thrown pottery industry and multiple churches\ud and cemeteries. The Torksey evidence allows for a radical reappraisal of the character of Viking\ud winter camps, and the legacy of the Viking Great Army for Anglo-Saxon England.

We extend the framework of mixed multi-unit combinatorial auctions to include time constraints, present an expressive bidding language, and show how to solve the winner determination problem for such auctions using integer programming. Mixed multi-unit combinatorial auctions are auctions where bidders can offer combinations of transformations of goods rather than just simple goods. This model has great potential for applications in the context of supply chain formation, which is further enhanced by the integration of time constraints. We consider different kinds of time constraints: they may be based on either time points or intervals, they may determine a relative ordering of transformations, they may relate transformations to absolute time points, and they may constrain the duration of transformations.

Establishing a robust chronology is fundamental to most palaeoenvironmental studies. However, the number and positioning of dated points is critical. Using a portable luminescence reader, it is possible to rapidly generate high resolution down core relative age profiles. Profiles of portable luminescence data from two coastal dunes were evaluated and compared with the results of particle size analysis, stratigraphy, and an independent historical chronology. Results show that, even in young samples, portable luminescence data is dominated by an age related signal which in homogeneous sediment need not be corrected for moisture, feldspar content changes or grain size. Profiles therefore provide relative chronologies from which accumulation phases can be established, and from which better targeted sampling and comparison to other sites could be undertaken. Even though they do not provide instant absolute chronologies, field-based portable luminescence profiling of Late Quaternary sites hold much potential to improve the resultant chronologies.

We propose new mechanisms that can be used by a demand response aggregator to flexibly shift the charging of electric vehicles (EVs) to times where cheap but intermittent renewable energy is in high supply. Here, it is important to consider the constraints and preferences of EV owners, while eliminating the scope for strategic behaviour. To achieve this, we propose, for the first time, a generic class of incentive mechanisms for settings with both varying marginal electricity costs and multi-dimensional preferences. We show these are dominant strategy incentive compatible, i.e., EV owners are incentivised to report their constraints and preferences truthfully. We also detail a specific instance of this class, show that it achieves ≈ 98% of the optimal in realistic scenarios and demonstrate how it can be adapted to trade off efficiency with profit.

28th European Photovoltaic Solar Energy Conference and Exhibition; 4333-4336, The combination of decreased or even omitted feed in tariffs and falling prices for PV systems have led electricity generation costs below electricity tariffs in many places across Europe. Consequently own consumption is gaining popularity not only in private homes but also in commercial applications. In addition the number of open space PV systems receiving feed in tariffs is decreasing. Hence large rooftop installations become interesting for project development companies and EPCs too. This paper discusses the various influencing factors on yield optimisation in regard to area utilisation and high own consumption rates. One major aspect is the orientation of the generator. In addition to a common tilt towards south, east-west orientated systems might be an interesting alternative in order to homogenise the diurnal variations. In addition to technical questions the economic side will be analysed too. Based on an exemplary load curve possible own consumption will be calculated. Consequently the value of the reduction of energy supply may be used for the analysis of the economic feasibility of the project. The study is based on comprehensive simulations considering all relevant technical and economic aspects. It shows ways to optimise the own consumption and the sustainable use of PV in the commercial sector.

Im Januar dieses Jahres hat das Helmholtz-Institut Freiberg für Ressourcentechnologie (HIF) in Kooperation mit der Technischen Universität Bergakademie Freiberg, der Bundesanstalt für Geowissenschaften und Rohstoffe (BGR), sowie dem Landesamt für Umwelt, Landwirtschaft und Geologie (LfULG) einen Antrag auf eine wissenschaftliche Aufsuchungsgenehmigung für ein Gebiet im Raum Geyer im Erzgebirgskreis beantragt. Das damit einhergehende Forschungsprojekt hat das Ziel, mittels geophysikalischer Verfahren das Rohstoffpotenzial des geologischen Untergrundes bis in eine Tiefe von ca. 500 m zu erfassen. Alle relevanten Daten, die im Rahmen dieser Aufsuchung erhoben werden, sollen genutzt werden, um ein 3D-Modell des geologischen Untergrunds im Aufsuchungsgebiet zu erstellen. Sowohl dieses Modell als auch die ihm zugrundeliegenden Daten sollen mit Abschluss des auf drei Jahre ausgelegten Projekts veröffentlicht werden.

poster; National audience

Liquid chromatography- tandem mass spectrometry (LC-MS/MS) is an important tool in characterizing the amino acid sequence and post-translational modifications of therapeutic antibodies. Identifying changes in the antibody is important in monitoring possible changes in activity and/or immunogenicity. However, sample preparation of antibodies for LC-MS/MS analysis can be difficult due to the tendency to form large aggregates, resistance to denaturing, and the formation of both very large and small peptides during enzymatic digestion. In this study, we have systematically investigated different trypsin digestion methods for chimeric immunoglobulin G (IgG) and compared differences in peptide identifications. METHODS: IgG, containing mouse and human sequence, was purchased from several vendors. Samples were prepared in Tris buffer, 0.1% RapiGest (Waters), or 6 M urea. Samples in Tris and 0.1% RapiGest were also heated to 60 °C. DTT and iodoacetamide were used to alkylate cysteine residues. Samples were digested with trypsin for 2 or 20 hours at 37 °C. Peptides were analyzed by SDS-PAGE and LC-MS/MS. Data were analyzed with NISTMSQC (NIST). RESULTS: The cysteine reduction and alkylation step was first optimized to improve alkylation and prevent protein precipitation. Urea was found to be a poor denaturant for chimeric IgG and resulted in incomplete digestion. Conversely, heating the samples improved digestions. The use of RapiGest during heating also prevented protein precipitation. Increased sequence coverage is observed in the difficult to digest CH3 region of the heavy chain upon heating. However, long digestion times result in the loss of the large, hydrophobic peptide in the CH1 region of the heavy chain. Only minor variations are observed under the different digest conditions for the light chain peptides. Therefore, heat denaturing in the presence of a surfactant followed by short digestion times were found to be optimal for chimeric IgG.

1. Motivation In den westlichen Industrieländern ist seit Jahren ein deutliches Wachstum koronarer Herzerkrankungen zu verzeichnen [ref:1], [ref:2]. Eine signifikante Anzahl davon führt durch einen ausgelösten Herz-Kreislauf-Stillstand zum Tod, da Rettungskräfte[for full text, please go to the a.m. URL], 1. Symposium ICT in der Notfallmedizin

Objective: Herniation can impair the ability of the lumbar disc to bear loads due to a reduced capacity to contain pressure in the presence of an annular defect and a loss of nucleus. Elements such as the facet-joints may become overloaded as a result. One goal of an annular closure device (ACD) is [for full text, please go to the a.m. URL], 63. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC), Joint Meeting mit der Japanischen Gesellschaft für Neurochirurgie (JNS)

Elevated levels of reactive oxygen species are found in most oncogenically transformed cells and are proposed to promote cellular transformation through mechanisms such as inhibition of phosphatases. BCR-ABL, the oncoprotein associated with the majority of chronic myelogenous leukemias, induces accumulation of intracellular ROS causing enhanced signaling downstream of PI3K. Previously we have shown that the transcription factor NF-κB is activated by BCR-ABL expression and is required for BCR-ABL-mediated cellular transformation. Inhibition of IKKβ and NF-κB leads to cell death through an unknown mechanism. Here, we analyze the potential involvement of NF-κB in moderating BCR-ABL-induced ROS levels to protect from death in response to cell stress. The data confirm that BCR-ABL promotes ROS levels and demonstrate that NF-κB prevents excessive ROS levels. Inhibition of NF-κB leads to an increase in ROS levels and to cell death controlled through ROS-induced JNK activity. The data demonstrate that one function for NF-κB in oncogenesis is the suppression of oncoprotein-induced ROS levels and that inhibition of NF-κB in some cancers, including CML, will increase ROS levels and promote cell death.

In service-oriented systems, such as grids and clouds, users are able to outsource complex computational tasks by procuring resources on demand from remote service providers. As these providers typically display highly heterogeneous performance characteristics, service procurement can be challenging when the consumer is uncertain about the computational requirements of its task a priori. Given this, we here argue that the key to addressing this problem is task migration, where the consumer can move a partially completed task from one provider to another. We show that doing this optimally is NP-hard, but we also propose two novel algorithms, based on new and established search techniques, that can be used by an intelligent agent to efficiently find the optimal solution in realistic settings. However, these algorithms require full information about the providers' quality of service and costs over time. Critically, as providers are usually self-interested agents, they may lie strategically about these to inflate profits. To address this, we turn to mechanism design and propose a payment scheme that incentivises truthfulness. In empirical experiments, we show that (i) task migration results in an up to 160% improvement in utility, (ii) full information about the providers' costs is necessary to achieve this and (iii) our mechanism requires only a small investment to elicit this information.

In this paper, we study a service procurement problem with uncertainty as to whether service providers are capable of completing a given task within a specifie deadline. This type of setting is often encountered in large and dynamic multi-agent systems, such as computational Grids or clouds. To effectively deal with this uncertainty, the consumer may dynamically and redundantly procure multiple services over time, in order to increase the probability of success, while at the same time balancing this with the additional procurement costs. However, in order to do this optimally, the consumer requires information about the providers costs and their success probabilities over time. This information is typically held privately by the providers and they may have incentives to misreport this, so as to increase their own profits To address this problem, we introduce a novel mechanism that incentivises self-interested providers to reveal their true costs and capabilities, and we show that this mechanism is ex-post incentive compatible, efficien and individually rational. However, for these properties to hold, it generally needs to compute the optimal solution, which can be intractable in large settings. Therefore, we show how we can generate approximate solutions while maintaining the economic properties of the mechanism. This approximation admits a polynomial-time solution that can be computed in seconds even for hundreds of providers, and we demonstrate empirically that it performs as well as the optimal in typical scenarios. In particularly challenging settings, we show that it still achieves 97% or more of the optimal. Copyright © 2010, International Foundation for Autonomous Agents and Multiagent Systems (www.ifaamas.org). All rights reserved.

The prevalence and mechanisms of antibiotic resistance of Helicobacter pylori have not yet been investigated in Uruguay. The objective of this study was to assess the susceptibility of H. pylori to the most frequently used antibiotics and to determine the mechanism of resistance to clarithromycin. Seventy-nine isolates were obtained from gastric biopsies of 50 adult patients during two periods, 2001 and 2006. The former group enrolled the general population (GP), the latter group Afro-descendant (AD) subjects. The minimum inhibitory concentrations of clarithromycin, amoxicillin, tetracycline, metronidazole, and levofloxacin were determined using the E-test technique. Amplification was achieved through PCR and nucleic acid sequencing to detect mutations in the site of action of clarithromycin in the rRNA gene 23S. No amoxicillin or tetracycline-resistant strains were found. Clarithromycin resistance was found in 12% of the patients overall: 19.4% resistance in AD patients and no resistance in the GP group. This difference was statistically significant. The highest resistance was seen with metronidazole (36%), present in similar proportions in the two groups: 36.8% (GP) and 35.5% (AD). One GP patient and one AD patient had levofloxacin-resistant strains. Sequencing analysis of gene 23S rRNA showed that only mutation in position 2143 was presented in all clarithromycin-resistant strains.

Emerging service-oriented technologies allow software agents to automatically procure distributed services to complete complex tasks. However, in many application scenarios, service providers demand financial remuneration, execution times are uncertain and consumers have deadlines for their tasks. In this paper, we address these issues by developing a novel approach that dynamically procures multiple, redundant services over time, in order to ensure success by the deadline. Specifically, we first present an algorithm for finding optimal procurement solutions, as well as a heuristic algorithm that achieves over 99% of the optimal and is capable of handling thousands of providers. Using experiments, we show that these algorithms achieve an improvement of up to 130% over current strategies that procure only single services. Finally, we consider settings where service costs are not known to the consumer, and introduce several mechanisms that incentivise providers to reveal their costs truthfully and that still achieve up to 95% efficiency.

24th European Photovoltaic Solar Energy Conference, 21-25 September 2009, Hamburg, Germany; 3716-3718, This paper aims to analyse the influence of diffuse shading on single axis tracking systems with a horizontal pivot and backtracking. This loss factor is not considered with available simulation programs and hence an error is made when doing yield simulations. The impact of this error is discussed within this paper.

As Grids become larger, more open and dynamic in nature, it will inevitably become necessary to deal with service failures and mitigate uncertainty in the execution of large service workflows. To this end, we propose a decision-theoretic approach to the provisioning problem (i.e., selecting service instances for the tasks of an abstract workflow). Our approach introduces redundancy into workflows to reduce the probability of failures, it dynamically re-provisions failed services and it negotiates advance agreements with providers when this is beneficial.

Regulatory compliance sets new requirements for business process management (BPM). Companies seek to enhance their corporate governance processes and are required to put in place measures for ensuring compliance to regulations. In this sense, this position paper (i) reviews the current work in the context of BPM systems and (ii) suggests future directions to improve the current status. During the literature review, techniques are classified as supporting forward or backward compliance. The latter is a post-execution compliance (i.e. based on execution histories of systems) and the former takes place at design- or run-time. In a nutshell, this position paper claims that four main aspects need to be incorporated by current compliance checking techniques: (i) an integrated approach able to cover the full BPM life-cycle, (ii) the support for compliance checks beyond control-flow-related aspects, (iii) intuitive graphical notations for business analysts, and (iv) embedding semantic technologies during the definition, deployment and executions of compliance checks.