Programmability and Performance of Parallel ECS-based Simulation of Multi-Agent Exploration Models

While the traditional objective of parallel/distributed simulation techniques has been mainly in improving performance and making very large models tractable, more recent research trends targeted complementary aspects, such as the “ease of programming”. Along this line, a recent proposal called Event and Cross State (ECS) synchronization, stands as a solution allowing to break the traditional programming rules proper of Parallel Discrete Event Simulation (PDES) systems, where the application code processing a specific event is only allowed to access the state (namely the memory image) of the target simulation object. In fact with ECS, the programmer is allowed to write ANSI-C event-handlers capable of accessing (in either read or write mode) the state of whichever simulation object included in the simulation model. Correct concurrent execution of events, e.g., on top of multi-core machines, is guaranteed by ECS with no intervention by the programmer, who is in practice exposed to a sequential-style programming model where events are processed one at a time, and have the ability to access the current memory image of the whole simulation model, namely the collection of the states of any involved object. This can strongly simplify the development of specific models, e.g., by avoiding the need for passing state information across concurrent objects in the form of events. In this article we investigate on both programmability and performance aspects related to developing/supporting a multi-agent exploration model on top of the ROOT-Sim PDES platform, which supports ECS

FAK activity sustains intrinsic and acquired ovarian cancer resistance to platinum chemotherapy.

Gene copy number alterations, tumor cell stemness, and the development of platinum chemotherapy resistance contribute to high-grade serous ovarian cancer (HGSOC) recurrence. Stem phenotypes involving Wnt-β-catenin, aldehyde dehydrogenase activities, intrinsic platinum resistance, and tumorsphere formation are here associated with spontaneous gains in Kras, Myc and FAK (KMF) genes in a new aggressive murine model of ovarian cancer. Adhesion-independent FAK signaling sustained KMF and human tumorsphere proliferation as well as resistance to cisplatin cytotoxicity. Platinum-resistant tumorspheres can acquire a dependence on FAK for growth. Accordingly, increased FAK tyrosine phosphorylation was observed within HGSOC patient tumors surviving neo-adjuvant chemotherapy. Combining a FAK inhibitor with platinum overcame chemoresistance and triggered cell apoptosis. FAK transcriptomic analyses across knockout and reconstituted cells identified 135 targets, elevated in HGSOC, that were regulated by FAK activity and β-catenin including Myc, pluripotency and DNA repair genes. These studies reveal an oncogenic FAK signaling role supporting chemoresistance

Load-sharing policies in parallel simulation of agent-based demographic models

Execution parallelism in agent-Based Simulation (ABS) allows to deal with complex/large-scale models. This raises the need for runtime environments able to fully exploit hardware parallelism, while jointly offering ABS-suited programming abstractions. In this paper, we target last-generation Parallel Discrete Event Simulation (PDES) platforms for multicore systems. We discuss a programming model to support both implicit (in-place access) and explicit (message passing) interactions across concurrent Logical Processes (LPs). We discuss different load-sharing policies combining event rate and implicit/explicit LPs’ interactions. We present a performance study conducted on a synthetic test case, representative of a class of agent-based models.Peer ReviewedPostprint (author's final draft

The association of health literacy with adherence in older 2 adults, and its role in interventions: a systematic meta-review

Background: Low health literacy is a common problem among older adults. It is often suggested to be associated with poor adherence. This suggested association implies a need for effective adherence interventions in low health literate people. However, previous reviews show mixed results on the association between low health literacy and poor adherence. A systematic meta-review of systematic reviews was conducted to study the association between health literacy and adherence in adults above the age of 50. Evidence for the effectiveness of adherence interventions among adults in this older age group with low health literacy was also explored. Methods: Eight electronic databases (MEDLINE, ERIC, EMBASE, PsycINFO, CINAHL, DARE, the Cochrane Library, and Web of Knowledge) were searched using a variety of keywords regarding health literacy and adherence. Additionally, references of identified articles were checked. Systematic reviews were included if they assessed the association between health literacy and adherence or evaluated the effectiveness of interventions to improve adherence in adults with low health literacy. The AMSTAR tool was used to assess the quality of the included reviews. The selection procedure, data-extraction, and quality assessment were performed by two independent reviewers. Seventeen reviews were selected for inclusion. Results: Reviews varied widely in quality. Both reviews of high and low quality found only weak or mixed associations between health literacy and adherence among older adults. Reviews report on seven studies that assess the effectiveness of adherence interventions among low health literate older adults. The results suggest that some adherence interventions are effective for this group. The interventions described in the reviews focused mainly on education and on lowering the health literacy demands of adherence instructions. No conclusions could be drawn about which type of intervention could be most beneficial for this population. Conclusions: Evidence on the association between health literacy and adherence in older adults is relatively weak. Adherence interventions are potentially effective for the vulnerable population of older adults with low levels of health literacy, but the evidence on this topic is limited. Further research is needed on the association between health literacy and general health behavior, and on the effectiveness of interventions

Substantial Conformational Change Mediated by Charge-Triad Residues of the Death Effector Domain in Protein-Protein Interactions

Protein conformational changes are commonly associated with the formation of protein complexes. The non-catalytic death effector domains (DEDs) mediate protein-protein interactions in a variety of cellular processes, including apoptosis, proliferation and migration, and glucose metabolism. Here, using NMR residual dipolar coupling (RDC) data, we report a conformational change in the DED of the phosphoprotein enriched in astrocytes, 15 kDa (PEA-15) protein in the complex with a mitogen-activated protein (MAP) kinase, extracellular regulated kinase 2 (ERK2), which is essential in regulating ERK2 cellular distribution and function in cell proliferation and migration. The most significant conformational change in PEA-15 happens at helices α2, α3, and α4, which also possess the highest flexibility among the six-helix bundle of the DED. This crucial conformational change is modulated by the D/E-RxDL charge-triad motif, one of the prominent structural features of DEDs, together with a number of other electrostatic and hydrogen bonding interactions on the protein surface. Charge-triad motif promotes the optimal orientation of key residues and expands the binding interface to accommodate protein-protein interactions. However, the charge-triad residues are not directly involved in the binding interface between PEA-15 and ERK2

Ecosystem productivity affected the spatiotemporal disappearance of Neanderthals in Iberia

What role did fluctuations play in biomass availability for secondary consumers in the disappearance of Neanderthals and the survival of modern humans? To answer this, we quantify the effects of stadial and interstadial conditions on ecosystem productivity and human spatiotemporal distribution patterns during the Middle to Upper Palaeolithic transition (50,000?30,000 calibrated years before the present) in Iberia. First, we used summed probability distribution, optimal linear estimation and Bayesian age modelling to reconstruct an updated timescale for the transition. Next, we executed a generalized dynamic vegetation model to estimate the net primary productivity. Finally, we developed a macroecological model validated with present-day observations to calculate herbivore abundance. The results indicate that, in the Eurosiberian region, the disappearance of Neanderthal groups was contemporaneous with a significant decrease in the available biomass for secondary consumers, and the arrival of the first Homo sapiens populations coincided with an increase in herbivore carrying capacity. During stadials, the Mediterranean region had the most stable conditions and the highest biomass of medium and medium?large herbivores. These outcomes support an ecological cause for the hiatus between the Mousterian and Aurignacian technocomplexes in Northern Iberia and the longer persistence of Neanderthals in southern latitudes.This research was funded by the European Research Council under the European Union’s Horizon 2020 Research and Innovation Programme (grant agreement number 818299; SUBSILIENCE project; https://www.subsilience.eu). We thank all of our colleagues from the EvoAdapta group for constant enriching discussions

Effects of Hypericum Perforatum, in a rodent model of periodontitis

<p>Abstract</p> <p>Background</p> <p><it>Hypericum perforatum </it>is a medicinal plant species containing many polyphenolic compounds, namely flavonoids and phenolic acids. In this study we evaluate the effect of <it>Hypericum perforatum </it>in animal model of periodontitis.</p> <p>Methods</p> <p>Periodontitis was induced in adult male Sprague-Dawley rats by placing a nylon thread ligature around the lower 1st molars. Hypericum perforatum was administered at the dose of 2 mg/kg os, daily for eight days. At day 8, the gingivomucosal tissue encircling the mandibular first molar was removed.</p> <p>Results</p> <p>Periodontitis in rats resulted in an inflammatory process characterized by edema, neutrophil infiltration and cytokine production that was followed by the recruitment of other inflammatory cells, production of a range of inflammatory mediators such as NF-κB and iNOS expression, the nitration of tyrosine residues and activation of the nuclear enzyme poly (ADP-ribose) polymerase; apoptosis and the degree of gingivomucosal tissues injury. We report here that Hypericum perforatum exerts potent anti-inflammatory effects significantly reducing all of the parameters of inflammation as described above.</p> <p>Conclusions</p> <p>Taken together, our results clearly demonstrate that treatment with Hypericum reduces the development of inflammation and tissue injury, events associated with periodontitis.</p

Condylar volume and surface in Caucasian young adult subjects

<p>Abstract</p> <p>Background</p> <p>There have been no quantitative standards for volumetric and surface measurements of the mandibular condyle in Caucasian population. However, the recently developed cone-beam computed tomography (CBCT) system allows measurement of these parameters with high accuracy.</p> <p>Methods</p> <p>CBCT was used to measure the condylar volume, surface and the volume to surface ratio, called the Morphometric Index (MI), of 300 temporo-mandibular joints (TMJ) in 150 Caucasian young adult subjects, with varied malocclusions, without pain or dysfunction of TMJs.</p> <p>Results</p> <p>The condylar volume was 691.26 ± 54.52 mm³in males and 669.65 ± 58.80 mm³in, and was significantly higher (<it>p</it>< 0.001) in the males. The same was observed for the condylar surface, although without statistical significance (406.02 ± 55.22 mm²in males and 394.77 ± 60.73 mm²in females).</p> <p>Furthermore, the condylar volume (693.61 ± 62.82 mm³) in the right TMJ was significantly higher than in the left (666.99 ± 48.67 mm³, <it>p </it>< 0.001) as was the condylar surface (411.24 ± 57.99 mm²in the right TMJ and 389.41 ± 56.63 mm²in the left TMJ; <it>t </it>= 3.29; <it>p </it>< 0.01). The MI is 1.72 ± 0.17 for the whole sample, with no significant difference between males and females or the right and left sides.</p> <p>Conclusion</p> <p>These data from temporomandibular joints of patients without pain or clinical dysfunction might serve as examples of normal TMJ's in the general population not seeking orthodontic care.</p