1,131 research outputs found
Availability-Guaranteed Service Function Chain Provisioning with Optional Shared Backups
The dynamic provisioning of Service Function Chain (SFC) using Virtual Network Functions (VNFs) is a challenging problem, especially for availability-constrained services. The provisioning of backup resources is often used to ensure that availability requirements are fulfilled. However, the assignment of backup resources should be carefully designed to avoid resource inefficiencies as much as possible.This paper proposes the Optional Backup with Shared Path and Shared Function (OBSPSF) strategy, which aims at improving resource efficiency while fulfilling the availability requirements of SFC requests. The strategy uses optional backup provisioning to ensure that backup resources are assigned only when strictly needed (i.e., when the SFC alone does not meet the availability constraint). Moreover, OBSPSF encourages backup sharing (among both connectivity and backup VNFs) to reduce the backup resource overhead. Results show that the strategy can accommodate orders-of-magnitude more services than benchmark heuristics from the literature
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The regulatory and transcriptional landscape associated with carbon utilization in a filamentous fungus.
Filamentous fungi, such as Neurospora crassa, are very efficient in deconstructing plant biomass by the secretion of an arsenal of plant cell wall-degrading enzymes, by remodeling metabolism to accommodate production of secreted enzymes, and by enabling transport and intracellular utilization of plant biomass components. Although a number of enzymes and transcriptional regulators involved in plant biomass utilization have been identified, how filamentous fungi sense and integrate nutritional information encoded in the plant cell wall into a regulatory hierarchy for optimal utilization of complex carbon sources is not understood. Here, we performed transcriptional profiling of N. crassa on 40 different carbon sources, including plant biomass, to provide data on how fungi sense simple to complex carbohydrates. From these data, we identified regulatory factors in N. crassa and characterized one (PDR-2) associated with pectin utilization and one with pectin/hemicellulose utilization (ARA-1). Using in vitro DNA affinity purification sequencing (DAP-seq), we identified direct targets of transcription factors involved in regulating genes encoding plant cell wall-degrading enzymes. In particular, our data clarified the role of the transcription factor VIB-1 in the regulation of genes encoding plant cell wall-degrading enzymes and nutrient scavenging and revealed a major role of the carbon catabolite repressor CRE-1 in regulating the expression of major facilitator transporter genes. These data contribute to a more complete understanding of cross talk between transcription factors and their target genes, which are involved in regulating nutrient sensing and plant biomass utilization on a global level
Hydrophobic Substituents of the Phenylmethylsulfamide Moiety Can Be Used for the Development of New Selective Carbonic Anhydrase Inhibitors
A new series of compounds containing a sulfamide moiety as zinc-binding group (ZBG) has been synthesized and tested for determining inhibitory properties against four human carbonic anhydrase (hCA) isoforms, namely, CAs I, II, IX, and XII. The X-ray structure of the cytosolic dominant isoform hCA II in complex with the best inhibitor of the series has also been determined providing further insights into sulfamide binding mechanism and confirming that such zinc-binding group, if opportunely derivatized, can be usefully exploited for obtaining new potent and selective CAIs. The analysis of the structure also suggests that for drug design purposes the but-2-yn-1-yloxy moiety tail emerges as a very interesting substituent of the phenylmethylsulfamide moiety due to its capability to establish strong van der Waals interactions with a hydrophobic cleft on the hCA II surface, delimited by residues Phe131, Val135, Pro202, and Leu204. Indeed, the complementarity of this tail with the cleft suggests that different substituents could be used to discriminate between isoforms having clefts with different sizes
The ectomycorrhizal fungus Pisolithus microcarpusencodes a microRNA involved in cross-kingdom gene silencing during symbiosis
Small RNAs (sRNAs) are known to regulate pathogenic plant-microbe interactions. Emerging evidence from the study of these model systems suggests that microRNAs (miRNAs) can be translocated between microbes and plants to facilitate symbiosis. The roles of sRNAs in mutualistic mycorrhizal fungal interactions, however, are largely unknown. In this study, we characterized miRNAs encoded by the ectomycorrhizal fungus Pisolithus microcarpus and investigated their expression during mutualistic interaction with Eucalyptus grandis. Using sRNA sequencing data and in situ miRNA detection, a novel fungal miRNA, Pmic_miR-8, was found to be transported into E. grandis roots after interaction with P. microcarpus. Further characterization experiments demonstrate that inhibition of Pmic_miR-8 negatively impacts the maintenance of mycorrhizal roots in E. grandis, while supplementation of Pmic_miR-8 led to deeper integration of the fungus into plant tissues. Target prediction and experimental testing suggest that Pmic_miR-8 may target the host NB-ARC domain containing transcripts, suggesting a potential role for this miRNA in subverting host signaling to stabilize the symbiotic interaction. Altogether, we provide evidence of previously undescribed cross-kingdom sRNA transfer from ectomycorrhizal fungi to plant roots, shedding light onto the involvement of miRNAs during the developmental process of mutualistic symbioses
Hipermídia educativa em acolhimento e classificação de risco obstétrico: validação de conteúdo e usabilidade
Objetivo: Validar o conteúdo e usabilidade de hipermídia educativa sobre acolhimento e classificação de risco obstétrico.Métodos: Estudo metodológico, desenvolvimento pelo modelo de design instrucional básico, realizado em cinco etapas. Participaram 22 juízes para validar conteúdo e usabilidade. Para a análise, foram utilizados o Índice de Validade de Conteúdo a System Usability Scale e o teste binomial.Resultados: No conteúdo obtiveram um Índice de Validade de Conteúdo de 0,96 e para e usabilidade obteve-se 91,9. Na avaliação global, todos os requisitos obtiveram 0,98 de índice.Conclusão: A hipermídia educativa desenvolvida apresenta evidência de validade e se constitui como recurso inovador para o processo de ensino e aprendizagem em Enfermagem.
Palavras-chave: Complicações na gravidez. Educação em enfermagem. Tecnologia educacional. Estudo de validação
Feasibility of double cropping system with camelina and sunflower in Serbia
The sustainable production of agricultural commodities, such as vegetable proteins and oils, is currently facing the challenge of developing new cropping strategies more e fficient in terms of water, nutrients, and land, while being able to increase the supply of domestic feedstocks. Double cropping of camelina (Camelina sativa L.), sown in the autumn, with sunflower (Helianthus annuus L.) can be proposed as a sustainable way to produce in the same growing season and land, multiple feedstocks for both energy, feed and food uses. A preliminary trial was conducted in Novi Sad (Serbia) during the 2018/19 growing season to test: yield performance, oil content and 1000 seed mass of two early sunflower hybrids (NS Dukat and NS H 7749) sown just after the harvest of two camelina varieties (NS Slatka and NS Zlatka which average yield was 920 kg/ha). Sunflower hybrids were also grown in the monocropping system as control. Both sunflower hybrids had higher seed yields in the monocropping system (+24%), but when considering the total yield of the two crops in the double cropping seed yield resulted slightly higher (+1-3%) than that of sunflower in the monocropping system. Although the average oil content and oil yield of sunflower was 6% and 27% higher in the monocropping system, respectively, the high nutritional value of camelina’s oil, which is rich
in omega-3, should be also carefully evaluated
Feasibility of double cropping system with camelina and sunflower in Serbia
The sustainable production of agricultural commodities, such as vegetable proteins and oils, is currently facing the challenge of developing new cropping strategies more e fficient in terms of water, nutrients, and land, while being able to increase the supply of domestic feedstocks. Double cropping of camelina (Camelina sativa L.), sown in the autumn, with sunflower (Helianthus annuus L.) can be proposed as a sustainable way to produce in the same growing season and land, multiple feedstocks for both energy, feed and food uses. A preliminary trial was conducted in Novi Sad (Serbia) during the 2018/19 growing season to test: yield performance, oil content and 1000 seed mass of two early sunflower hybrids (NS Dukat and NS H 7749) sown just after the harvest of two camelina varieties (NS Slatka and NS Zlatka which average yield was 920 kg/ha). Sunflower hybrids were also grown in the monocropping system as control. Both sunflower hybrids had higher seed yields in the monocropping system (+24%), but when considering the total yield of the two crops in the double cropping seed yield resulted slightly higher (+1-3%) than that of sunflower in the monocropping system. Although the average oil content and oil yield of sunflower was 6% and 27% higher in the monocropping system, respectively, the high nutritional value of camelina’s oil, which is rich in omega-3, should be also carefully evaluated.This is a poster presented at the 20th International Sunflower Conference, held on 20-23 June 2022 in Novi Sad, Serbia. The published conference paper is available at [http://fiver.ifvcns.rs/handle/123456789/2907]
Tolerability and efficacy of vortioxetine versus SSRIs in elderly with major depression. Study protocol of the VESPA study: a pragmatic, multicentre, open-label, parallel-group, superiority, randomized trial
Depression is a highly prevalent condition in the elderly, with a vast impact on quality of life, life expectancy, and medical outcomes. Selective serotonin reuptake inhibitors (SSRIs) are the most commonly prescribed agents in this condition and, although generally safe, tolerability issues cannot be overlooked. Vortioxetine is an antidepressant with a novel mechanism of action. Based on studies to date, it may have a promising tolerability profile in the elderly, as it does not adversely affect psychomotor or cognitive performance and does not alter cardiovascular and endocrine parameters. The present study aims to assess the tolerability profile of vortioxetine in comparison with the SSRIs considered as a single group in elderly participants with depression. The rate of participants withdrawing from treatment due to adverse events after 6 months of follow up will be the primary outcome
Tolerability of vortioxetine compared to selective serotonin reuptake inhibitors in older adults with major depressive disorder (VESPA): a randomised, assessor-blinded and statistician-blinded, multicentre, superiority trial.
BACKGROUND
Major depressive disorder (MDD) is prevalent and disabling among older adults. Standing on its tolerability profile, vortioxetine might be a promising alternative to selective serotonin reuptake inhibitors (SSRIs) in such a vulnerable population.
METHODS
We conducted a randomised, assessor- and statistician-blinded, superiority trial including older adults with MDD. The study was conducted between 02/02/2019 and 02/22/2023 in 11 Italian Psychiatric Services. Participants were randomised to vortioxetine or one of the SSRIs, selected according to common practice. Treatment discontinuation due to adverse events after six months was the primary outcome, for which we aimed to detect a 12% difference in favour of vortioxetine. The study was registered in the online repository clinicaltrials.gov (NCT03779789).
FINDINGS
The intention-to-treat population included 179 individuals randomised to vortioxetine and 178 to SSRIs. Mean age was 73.7 years (standard deviation 6.1), and 264 participants (69%) were female. Of those on vortioxetine, 78 (44%) discontinued the treatment due to adverse events at six months, compared to 59 (33%) of those on SSRIs (odds ratio 1.56; 95% confidence interval 1.01-2.39). Adjusted and per-protocol analyses confirmed point estimates in favour of SSRIs, but without a significant difference. With the exception of the unadjusted survival analysis showing SSRIs to outperform vortioxetine, secondary outcomes provided results consistent with a lack of substantial safety and tolerability differences between the two arms. Overall, no significant differences emerged in terms of response rates, depressive symptoms and quality of life, while SSRIs outperformed vortioxetine in terms of cognitive performance.
INTERPRETATION
As opposed to what was previously hypothesised, vortioxetine did not show a better tolerability profile compared to SSRIs in older adults with MDD in this study. Additionally, hypothetical advantages of vortioxetine on depression-related cognitive symptoms might be questioned. The study's statistical power and highly pragmatic design allow for generalisability to real-world practice.
FUNDING
The study was funded by the Italian Medicines Agency within the "2016 Call for Independent Drug Research"
Behavioural patterns in allergic rhinitis medication in Europe : A study using MASK-air(R) real-world data
Background Co-medication is common among patients with allergic rhinitis (AR), but its dimension and patterns are unknown. This is particularly relevant since AR is understood differently across European countries, as reflected by rhinitis-related search patterns in Google Trends. This study aims to assess AR co-medication and its regional patterns in Europe, using real-world data. Methods We analysed 2015-2020 MASK-air(R) European data. We compared days under no medication, monotherapy and co-medication using the visual analogue scale (VAS) levels for overall allergic symptoms ('VAS Global Symptoms') and impact of AR on work. We assessed the monthly use of different medication schemes, performing separate analyses by region (defined geographically or by Google Trends patterns). We estimated the average number of different drugs reported per patient within 1 year. Results We analysed 222,024 days (13,122 users), including 63,887 days (28.8%) under monotherapy and 38,315 (17.3%) under co-medication. The median 'VAS Global Symptoms' was 7 for no medication days, 14 for monotherapy and 21 for co-medication (p < .001). Medication use peaked during the spring, with similar patterns across different European regions (defined geographically or by Google Trends). Oral H-1-antihistamines were the most common medication in single and co-medication. Each patient reported using an annual average of 2.7 drugs, with 80% reporting two or more. Conclusions Allergic rhinitis medication patterns are similar across European regions. One third of treatment days involved co-medication. These findings suggest that patients treat themselves according to their symptoms (irrespective of how they understand AR) and that co-medication use is driven by symptom severity.Peer reviewe
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