A Language for Agent-based Discrete-event Modeling and Simulation of Linked Lives

In agent-based modeling and simulation, discrete-time methods prevail. While there is a need to cover the agents’ dynamics in continuous time, commonly used agent-based modeling frameworks offer little support for discrete-event simulation. Here, we present a formal syntax and semantics of the language ML3 (Modeling Language for Linked Lives) for modeling and simulating multi-agent systems as discrete-event systems. The language focuses on applications in demography, such as migration processes, and considers this discipline’s specific requirements. These include the importance of life courses being linked and the age-dependency of activities and events. The developed abstract syntax of the language combines the metaphor of agents with guarded commands. Its semantics is defined in terms of Generalized Semi-Markov Processes. The concrete language has been realized as an external domain-specific language. We discuss implications for efficient simulation algorithms and elucidate benefits of formally defining domain-specific languages for modeling and simulation.

Quingo: A Programming Framework for Heterogeneous Quantum-Classical Computing with NISQ Features

The increasing control complexity of Noisy Intermediate-Scale Quantum (NISQ) systems underlines the necessity of integrating quantum hardware with quantum software. While mapping heterogeneous quantum-classical computing (HQCC) algorithms to NISQ hardware for execution, we observed a few dissatisfactions in quantum programming languages (QPLs), including difficult mapping to hardware, limited expressiveness, and counter-intuitive code. In addition, noisy qubits require repeatedly performed quantum experiments, which explicitly operate low-level configurations, such as pulses and timing of operations. This requirement is beyond the scope or capability of most existing QPLs. We summarize three execution models to depict the quantum-classical interaction of existing QPLs. Based on the refined HQCC model, we propose the Quingo framework to integrate and manage quantum-classical software and hardware to provide the programmability over HQCC applications and map them to NISQ hardware. We propose a six-phase quantum program life-cycle model matching the refined HQCC model, which is implemented by a runtime system. We also propose the Quingo programming language, an external domain-specific language highlighting timer-based timing control and opaque operation definition, which can be used to describe quantum experiments. We believe the Quingo framework could contribute to the clarification of key techniques in the design of future HQCC systems.

A Direct Assessment of the External Domain of Food Environments in the National Capital Region of India

Data on food environments in India and other low- and middle-income countries are scarce. The objective of this study was to assess the four dimensions of the external domain of food environments (availability, price, vendor and product properties, and marketing) in food establishments in the National Capital Region of India. The assessment focused on fruits, vegetables, and ultra-processed foods. The 60 food establishments surveyed were categorized as stores, restaurants, or mobile food vendors. Only 13.3% of food establishments sold fruits and vegetables. Stores were more likely to sell vegetables than mobile food vendors (14.8 vs. 6.2%, respectively) and sold a greater variety of both fruits and vegetables as compared to mobile food vendors [mean (SD) of 8.6 (3.2) fruits and 18.6 (9.2) vegetables available at stores vs. 5.5 (5.7) fruits and 25 vegetables available at the one mobile food vendor who sold vegetables]. However, these healthy food items were more expensive at stores. The availability (100% of stores, 12.5% of mobile food vendors, and 12.5% of restaurants) and variety (156 types) of ultra-processed foods across food establishments were higher than fruits and vegetables. A greater percentage of food establishments displayed advertisements for ultra-processed foods as compared to unprocessed or minimally processed foods such as fruits and vegetables. The National Capital Region of India has an unhealthy food environment. Regulations that limit the availability of ultra-processed foods and improve the availability and affordability of fruits and vegetables are needed to reverse the rising tide of chronic non-communicable diseases in this setting.

SOSIP trimer-specific antibodies isolated from a SHIV-infected monkey with versus without a pre-blocking step with gp41

BG505 SOSIP.664 (hereafter referred to as SOSIP), a stabilized trimeric mimic of the HIV-1 envelope spike resembling the native viral spike, is a useful tool for isolating anti-HIV-1 neutralizing antibodies. We screened long-term SHIV-AD8 infected rhesus monkeys for potency and breadth of serum neutralizing activity against autologous and heterologous viruses: SHIV-AD8, HIV-1 YU2, HIV-1 JR-CSF, and HIV-1 NL4-3. Monkey rh2436 neutralized all viruses tested and showed strong reactivity to the SOSIP trimer, suggesting this was a promising candidate for attempts at monoclonal antibody (mAb) isolation. Monoclonal antibodies were isolated by performing single B-cell sorts from peripheral blood mononuclear cells (PBMC) by FACS using the SOSIP trimer as a probe. An initial round of sorted cells revealed the majority of isolated mAbs were directed to the gp41 external domain portion of the SOSIP trimer and were mostly non-neutralizing against tested isolates. A second sort was performed, introducing a gp41 blocking step prior to PBMC staining and FACS sorting. These isolated mAbs bound SOSIP trimer but were no longer directed to the gp41 external domain portion. A significantly higher proportion of mAbs with neutralizing activity were obtained with this strategy. Our data show this pre-blocking step with gp41 greatly increases the yield of non-gp41 reactive, SOSIP- specific mAbs and increases the likelihood of isolating mAbs with neutralizing activity. Importance Recent advancements in the field have focused on the isolation and use of broadly neutralizing antibodies for both prophylaxis and therapy. Finding a useful probe to isolate broad potent neutralizing antibodies while avoiding non-neutralizing antibodies is important. The SOSIP trimer has been shown to be a great tool for this purpose because it binds known broadly neutralizing antibodies. However, the SOSIP trimer can isolate non-neutralizing antibodies as well, including gp41-specific mAbs. Introducing a pre-blocking step with gp41 recombinant protein decreased the percent of gp41-specific antibodies isolated with SOSIP probe, as well as increased the number of neutralizing antibodies isolated. This method could be used as a tool to increase the chances of isolating neutralizing antibodies.

Sequences in the cytoplasmic tail of SARS-CoV-2 Spike facilitate expression at the cell surface and syncytia formation

The Spike (S) protein of SARS-CoV-2 binds ACE2 to direct fusion with host cells. S comprises a large external domain, a transmembrane domain, and a short cytoplasmic tail. Understanding the intracellular trafficking of S is relevant to SARS-CoV-2 infection, and to vaccines expressing full-length S from mRNA or adenovirus vectors. Here we report a proteomic screen for cellular factors that interact with the cytoplasmic tail of S. We confirm interactions with the COPI and COPII vesicle coats, ERM family actin regulators, and the WIPI3 autophagy component. The COPII binding site promotes exit from the endoplasmic reticulum, and although binding to COPI should retain S in the early Golgi where viral budding occurs, there is a suboptimal histidine residue in the recognition motif. As a result, S leaks to the surface where it accumulates and can direct the formation of multinucleate syncytia. Thus, the trafficking signals in the tail of S indicate that syncytia play a role in the SARS-CoV-2 lifecycle.

Novel Approach to Measure Internal Power Domain PG Route Weakness

Grid weakness measurement is an extremely important process in the modern-day VLSI design flow. In designs that contain power gating switches, there are additional challenges. It is desirable to find the PG grid weakness of only the gated domain. The tools used in the industry typically measure the total voltage drops from the bump location to the transistor pin. This voltage drop is the summation of the voltage drops in the external domain, switch pin network, and internal domain. This paper explores the ways to measure the internal pin domain voltage exclusively. Ansys Totem tool is used for simulation. Finally, the simulation results are presented to propose the effectiveness and accuracy of the given solution.

Plio–Quaternary Structural Evolution of the Outer Sector of the Marche Apennines South of the Conero Promontory, Italy

Some new results and preliminary remarks about the Plio–Quaternary structural and evolutionary characteristics of the outer Marche Apennines south in the Conero promontory are presented in this study. The present analysis is based on several subsurface seismic reflection profiles and well data, kindly provided by ENI S.p.A. and available on the VIDEPI list, together with surface geologic–stratigraphic knowledge of Plio–Quaternary evolution from the literature. Examples of negative vs. positive reactivation of inherited structures in fold and thrust belts are highlighted. Here, we present an example from the external domain of the Marche Apennines, which displays interesting reactivation examples from the subsurface geology explored. The study area shows significant evolutionary differences with respect to the northern sector of the Marche region previously investigated by the same research group. The areal distribution of the main structures changes north and south of the ENE–WSW oriented discontinuity close to the Conero promontory. Based on the old tripartite classification of the Pliocene, the results of this work suggest a strong differential subsidence with extension occurring during the Early Pliocene and principal compressive deformation starting from the Middle Pliocene and decreasing or ceasing during the Quaternary. The main structure in this area is the NNW–SSE Coastal Structure, which is composed of E-vergent shallow thrusts and high-angle deep-seated normal faults underneath. An important right-lateral strike–slip component along this feature is also suggested, which is compatible with the principal NNE–SSW shortening direction. As mentioned, the area is largely characterized by tectonic inversion. Starting from Middle Pliocene, most of the Early Pliocene normal faults became E-vergent thrusts.

Missing lawsonite found ! Resolving paradoxes of the metamorphic structure of the Western Alps

<p>Lawsonite is a strongly hydrated (12 weight % H<sub>2</sub>O) Ca- and Al-rich silicate, exclusively stable along low P/T gradients, typical of subduction zones. The distribution and preservation of lawsonite at the scale of a subduction/collision belt reflect the occurrence of rocks with favourable chemical composition (mainly hydrothermally altered metabasalts and marly limestones (i.e. calcschists), two lithologies especially common in the oceanic units) and their pressure-temperature-fluid history (with preservation favoured by decreasing T during decompression).</p><p>The distribution of lawsonite in the Western Alps has been investigated since several decades. In the blueschist-facies units from the South-Western Alps (Queyras, Ubaye), lawsonite is well preserved in the external domain, at the contact with the Briançonnais domain, but is largely pseudomorphed in the more internal domain, at the contact with the Viso Unit. Further North, neither lawsonite nor lawsonite pseudomorphs have been reported in the supposedly blueschist-facies Combin Zone, taken by most studies as an equivalent of the Queyras-Ubaye units. This constitutes a paradox with respect to the overall metamorphic structure of the Alpine belt.</p><p>This study documents for the first time several occurrences of lawsonite and garnet in the calcschists from the Combin Zone. Field and metamorphic data (thermodynamic modelling and Raman spectroscopy on carbonaceous material) point to the occurrence of two tectonometamorphic units within the Combin Zone, characterised by distinct geometry, lithological content and Alpine P-T conditions.</p><p>In the higher grade unit, lawsonite and garnet were stable at peak P-T conditions (~14-16 kbar and ~460-490 °C) at very low X(CO<sub>2</sub>) values. Although lawsonite is systematically pseudomorphed, we have been able to recognize hourglass zoning in lawsonite or preservation of an internal fabric associated with the prograde ductile deformation.</p><p>The lower grade unit (~8 ± 1 kbar ~370-400 °C) is discontinuously exposed along the western base of the Dent Blanche nappe and records Alpine P-T conditions similar to those reached by the Dent Blanche nappe (Manzotti et al. 2020).</p><p>Our data show that lawsonite is not missing in the Combin Zone, and resolve a paradox about the large-scale metamorphic structure of the Alps.</p><p> </p><p>Manzotti, P., Ballèvre, M., Pitra, P., Müntener, O., Putlitz, B., Robyr, M. (2020). Journal of Petrology, egaa044, https://doi.org/10.1093/petrology/egaa044.</p>

Paleotemperature investigation of the Variscan southern external domain: the case of the Montagne Noire (France)

The Montagne Noire located in the southern part of the French Massif Central represents the northern part of the South-Variscan Foreland. It is subdivided into three parts. The granite-migmatite Axial Zone dome is surrounded by non- or weakly metamorphosed Paleozoic sedimentary series. Both northern and southern flanks of the Montagne Noire dome are deformed by km-scale, south to southeast facing recumbent folds and thrusts sheets. The Raman Spectroscopy of Carbonaceous Material (RSCM) method, carried out in the low-grade metamorphic rocks of the southern flank of the Montagne Noire, yielded temperatures comprised between 400°C near the dome, and 230°C in the southern domain. Three Raman geothermometers were used to cover this temperature range. RSCM temperatures comply qualitatively with previous estimates based on illite crystallinity, conodont colour alteration, and fluid inclusions carried out in the same area, which document a metamorphic temperature increase towards the dome. The isotherms cut across the different nappe contacts and are oriented parallel to the southern margin of the Axial Zone. This temperature distribution supports the idea that the thermal structure was acquired during the Axial Zone dome emplacement. The thermal structure acquired during the recumbent folds emplacement and burial of the sedimentary series is totally overprinted by the doming. In addition, in a domain relatively remote from the Axial Zone dome, the RSCM measurements yielded significantly higher temperatures than illite crystallinity. This discrepancy points to a higher sensitivity of RSCM to short-lived thermal events than illite crystallinity, possibly because of more efficient kinetics of the carbonization reaction. On the other hand, high RSCM temperatures analysed far from the Axial Zone, between 300°C and 360°C, could be explained by the presence of granitic plutons under the foreland basin.