Airport Congestion Mitigation through Dynamic Control of Runway Configurations and of Arrival and Departure Service Rates under Stochastic Operating Conditions

The high levels of flight delays require the implementation of airport congestion mitigation tools. In this paper, we optimize the utilization of airport capacity at the tactical level in the face of operational uncertainty. We formulate an original Dynamic Programming model that selects jointly and dynamically runway configurations and the balance of arrival and departure service rates at a busy airport to minimize congestion costs, under stochastic queue dynamics and stochastic operating conditions. The control is exercised as a function of flight schedules, of arrival and departure queue lengths and of weather and wind conditions. We implement the model in a realistic setting at JFK Airport. The exact Dynamic Programming algorithm terminates within reasonable time frames. In addition, we implement an approximate one-step look-ahead algorithm that considerably accelerates the execution of the model and results in close-to-optimal policies. In combination, these solution algorithms enable the on-line implementation of the model using real-time information on flight schedules and meteorological conditions. The application of the model shows that the optimal policy is path-dependent, i.e., it depends on prior decisions and on the stochastic evolution of arrival and departure queues during the day. This underscores the theoretical and practical need for integrating operating stochasticity into the decision-making framework. From comparisons with an alternative model based on deterministic queue dynamics, we estimate the benefit of considering queue stochasticity at 5% to 20%. Finally, comparisons with advanced heuristics aimed to imitate actual operating procedures suggest that the model can yield significant cost savings, estimated at 20% to 30%

A dimeric form of the HIV-1 antibody 2G12 elicits potent antibody-dependent cellular cytotoxicity

Objective: Increasing data support a role for antibody-dependent cellular cytotoxicity (ADCC) in controlling HIV-1 infection. We recently isolated a naturally occurring dimeric form of the anti-HIV-1 antibody 2G12 and found it to be significantly more potent than 2G12 monomer in neutralizing primary virus strains. However, given the unusual structure of dimeric 2G12 with two Fc regions, it was not clear whether 2G12 dimer could bind to the CD16 Fc receptor on ADCC effector cells or trigger ADCC. Here we compared the in-vitro ADCC activities of 2G12 monomer and dimer and investigated the effects of including ADCC-enhancing mutations in both forms of 2G12. Methods: An in-vitro ADCC assay using target cells stably expressing gp160 was developed to evaluate the activities of 2G12 monomer and dimer with and without ADCC-enhancing mutations that increase the CD16-binding affinity of the 2G12 Fc region. Results: Both 2G12 monomer and 2G12 dimer elicited ADCC, although the dimer showed increased potency [lower half-maximal concentration (EC50)] in triggering ADCC, thus confirming its ability to bind CD16 and trigger ADCC. The ADCC-enhancing mutations improved the ADCC activity of 2G12 monomer more than 2G12 dimer such that their EC50 values were nearly equal. However, no increase in nonspecific ADCC activity was observed using 2G12 IgGs with these mutations. Conclusion: Given the likelihood that ADCC plays a role in protecting against initial infection and/or controlling chronic infection, these data suggest 2G12 dimers and/or addition of ADCC-enhancing mutations could augment the prophylactic and/or therapeutic potential of 2G12

Binding of guide piRNA triggers methylation of the unstructured N-terminal region of Aub leading to assembly of the piRNA amplification complex

Piwi proteins use guide piRNAs to repress selfish genomic elements, protecting the genomic integrity of gametes and ensuring the fertility of animal species. Efficient transposon repression depends on amplification of piRNA guides in the ping-pong cycle, which in Drosophila entails tight cooperation between two Piwi proteins, Aub and Ago3. Here we show that post-translational modification, symmetric dimethylarginine (sDMA), of Aub is essential for piRNA biogenesis, transposon silencing and fertility. Methylation is triggered by loading of a piRNA guide into Aub, which exposes its unstructured N-terminal region to the PRMT5 methylosome complex. Thus, sDMA modification is a signal that Aub is loaded with piRNA guide. Amplification of piRNA in the ping-pong cycle requires assembly of a tertiary complex scaffolded by Krimper, which simultaneously binds the N-terminal regions of Aub and Ago3. To promote generation of new piRNA, Krimp uses its two Tudor domains to bind Aub and Ago3 in opposite modification and piRNA-loading states. Our results reveal that post-translational modifications in unstructured regions of Piwi proteins and their binding by Tudor domains that are capable of discriminating between modification states is essential for piRNA biogenesis and silencing

Physiological capabilities of cryoconite hole microorganisms

Cryoconite holes are miniature freshwater aquatic ecosystems that harbor a relatively diverse microbial community. This microbial community can withstand the extreme conditions of the supraglacial environment, including fluctuating temperatures, extreme and varying geochemical conditions and limited nutrients. We analyzed the physiological capabilities of microbial isolates from cryoconite holes from Antarctica, Greenland, and Svalbard in selected environmental conditions: extreme pH, salinity, freeze-thaw and limited carbon sources, to identify their physiological limits. The results suggest that heterotrophic microorganisms in cryoconite holes are well adapted to fast-changing environmental conditions, by surviving multiple freeze-thaw cycles, a wide range of salinity and pH conditions and scavenging a variety of organic substrates. Under oxic and anoxic conditions, the communities grew well in temperatures up to 30°C, although in anoxic conditions the community was more successful at colder temperatures (0.2°C). The most abundant cultivable microorganisms were facultative anaerobic bacteria and yeasts. They grew in salinities up to 10% and in pH ranging from 4 to 10.5 (Antarctica), 2.5 to 10 (Svalbard), and 3 to 10 (Greenland). Their growth was sustained on at least 58 single carbon sources and there was no decrease in viability for some isolates after up to 100 consecutive freeze-thaw cycles. The elevated viability of the anaerobic community in the lowest temperatures indicates they might be key players in winter conditions or in early melt seasons, when the oxygen is potentially depleted due to limited flow of meltwater. Consequently, facultative anaerobic heterotrophs are likely important players in the reactivation of the community after the polar night. This detailed physiological investigation shows that despite inhabiting a freshwater environment, cryoconite microorganisms are able to withstand conditions not typically encountered in freshwater environments (namely high salinities or extreme pH), making them physiologically more similar to arid soil communities. The results also point to a possible resilience of the most abundant microorganisms of cryoconite holes in the face of rapid change regardless of the location

Aub and Ago3 Are Recruited to Nuage through Two Mechanisms to Form a Ping-Pong Complex Assembled by Krimper

In Drosophila, two Piwi proteins, Aubergine (Aub) and Argonaute-3 (Ago3), localize to perinuclear “nuage” granules and use guide piRNAs to target and destroy transposable element transcripts. We find that Aub and Ago3 are recruited to nuage by two different mechanisms. Aub requires a piRNA guide for nuage recruitment, indicating that its localization depends on recognition of RNA targets. Ago3 is recruited to nuage independently of a piRNA cargo and relies on interaction with Krimper, a stable component of nuage that is able to aggregate in the absence of other nuage proteins. We show that Krimper interacts directly with Aub and Ago3 to coordinate the assembly of the ping-pong piRNA processing (4P) complex. Symmetrical dimethylated arginines are required for Aub to interact with Krimper, but they are dispensable for Ago3 to bind Krimper. Our study reveals a multi-step process responsible for the assembly and function of nuage complexes in piRNA-guided transposon repression

Binding of guide piRNA triggers methylation of the unstructured N-terminal region of Aub leading to assembly of the piRNA amplification complex

Piwi proteins use guide piRNAs to repress selfish genomic elements, protecting the genomic integrity of gametes and ensuring the fertility of animal species. Efficient transposon repression depends on amplification of piRNA guides in the ping-pong cycle, which in Drosophila entails tight cooperation between two Piwi proteins, Aub and Ago3. Here we show that post-translational modification, symmetric dimethylarginine (sDMA), of Aub is essential for piRNA biogenesis, transposon silencing and fertility. Methylation is triggered by loading of a piRNA guide into Aub, which exposes its unstructured N-terminal region to the PRMT5 methylosome complex. Thus, sDMA modification is a signal that Aub is loaded with piRNA guide. Amplification of piRNA in the ping-pong cycle requires assembly of a tertiary complex scaffolded by Krimper, which simultaneously binds the N-terminal regions of Aub and Ago3. To promote generation of new piRNA, Krimp uses its two Tudor domains to bind Aub and Ago3 in opposite modification and piRNA-loading states. Our results reveal that post-translational modifications in unstructured regions of Piwi proteins and their binding by Tudor domains that are capable of discriminating between modification states is essential for piRNA biogenesis and silencing

Piwi induces piRNA-guided transcriptional silencing and establishment of a repressive chromatin state

In the metazoan germline, piwi proteins and associated piwi-interacting RNAs (piRNAs) provide a defense system against the expression of transposable elements. In the cytoplasm, piRNA sequences guide piwi complexes to destroy complementary transposon transcripts by endonucleolytic cleavage. However, some piwi family members are nuclear, raising the possibility of alternative pathways for piRNA-mediated regulation of gene expression. We found that Drosophila Piwi is recruited to chromatin, colocalizing with RNA polymerase II (Pol II) on polytene chromosomes. Knockdown of Piwi in the germline increases expression of transposable elements that are targeted by piRNAs, whereas protein-coding genes remain largely unaffected. Derepression of transposons upon Piwi depletion correlates with increased occupancy of Pol II on their promoters. Expression of piRNAs that target a reporter construct results in a decrease in Pol II occupancy and an increase in repressive H3K9me3 marks and heterochromatin protein 1 (HP1) on the reporter locus. Our results indicate that Piwi identifies targets complementary to the associated piRNA and induces transcriptional repression by establishing a repressive chromatin state when correct targets are found

The Setting Questionnaire for the Ayahuasca Experience: Questionnaire Development and Internal Structure

The growing interest in research on psychedelic consumption in naturalistic contexts and their possible medical and therapeutic benefits requires assessment of the relationships between the substance and the individual who consumes it (set) and its context of use (setting). This study provides a novel measurement scale for the setting of Ayahuasca consumption, the Setting Questionnaire for the Ayahuasca Experience (SQAE), and examines its psychometric properties. Construction of the scale began with a literature review, followed by interviews on 19 Ayahuasca users from different backgrounds and different consumption experience, and an online survey for quantitative data collection (n = 2,994). Exploratory Graph Analysis (EGA) was used to investigate the questionnaire's dimensional structure with (n = 1,497, half of the sample), and multidimensional item response theory (MIRT) was used to compare the fit of the theoretical dimensions with the EGA proposed dimensions (n = 1,497, independent other half). EGA identified six dimensions, which corresponded partially to the theorized model (Leadership, Decoration, Infrastructure, Comfort, Instruction, and Social). The MIRT comparison found that the proposed theoretical model fit significantly better than the EGA model, providing support for the former (χ2/df = 1,967; CFI = 0,972; TLI = 0,969; RMSEA = 0,059; WRMR = 1,087). Our findings present evidence of validity of this instrument, justifying its use for future research on the influence of the setting during the ayahuasca experience. Its findings may provide a basis for expanding the settings investigated in the use of psychedelics in general

Circular Supply Chains in Emerging Economies – a comparative study of packaging recovery ecosystems in China and Brazil

This paper provides a circular supply chain perspective of packaging recovery ecosystems being implemented by Tetra Pak, a prime global player in the food packaging industry, in two major emerging economies: China and Brazil. The circular supply chain archetype considered in the research allowed a consistent comparative analysis of Tetra Pak’s circular supply chains in both countries. Through a case study approach, the research provides theoretical propositions and learning points that are valuable for academics and practitioners interested in the Chinese and Brazilian markets as well as in the supply chains supporting recovery ecosystems in the packaging industry. In particular, the distinct environments in the Chinese and Brazilian markets render Tetra Pak opportunities to design circular supply chains in different ways showing adaptation and learning to local market characteristics. The industrial perspectives from these emerging economies add to the contributions offered in the paper. Overall, the conceptual considerations and practical recommendations presented in the paper provide useful insights for the development of further studies and implementation of industrial practices advocated by the circular economy

Avian Influenza Viruses in Water Birds, Africa1

We report the first large-scale surveillance of avian influenza viruses in water birds conducted in Africa. This study shows evidence of avian influenza viruses in wild birds, both Eurasian and Afro-tropical species, in several major wetlands of Africa