Dense agent-based HPC simulation of cell physics and signaling with real-time user interactions

Introduction: Distributed simulations of complex systems to date have focused on scalability and correctness rather than interactive visualization. Interactive visual simulations have particular advantages for exploring emergent behaviors of complex systems. Interpretation of simulations of complex systems such as cancer cell tumors is a challenge and can be greatly assisted by using “built-in” real-time user interaction and subsequent visualization.Methods: We explore this approach using a multi-scale model which couples a cell physics model with a cell signaling model. This paper presents a novel communication protocol for real-time user interaction and visualization with a large-scale distributed simulation with minimal impact on performance. Specifically, we explore how optimistic synchronization can be used to enable real-time user interaction and visualization in a densely packed parallel agent-based simulation, whilst maintaining scalability and determinism. We also describe the software framework created and the distribution strategy for the models utilized. The key features of the High-Performance Computing (HPC) simulation that were evaluated are scalability, deterministic verification, speed of real-time user interactions, and deadlock avoidance.Results: We use two commodity HPC systems, ARCHER (118,080 CPU cores) and ARCHER2 (750,080 CPU cores), where we simulate up to 256 million agents (one million cells) using up to 21,953 computational cores and record a response time overhead of ≃350 ms from the issued user events.Discussion: The approach is viable and can be used to underpin transformative technologies offering immersive simulations such as Digital Twins. The framework explained in this paper is not limited to the models used and can be adapted to systems biology models that use similar standards (physics models using agent-based interactions, and signaling pathways using SBML) and other interactive distributed simulations

Middle-Ear Function with Tympanic-Membrane Perforations. II. A Simple Model.

A quantitative model of the human middle ear with a tympanic-membrane ~TM! perforation is developed. The model is constrained by several types of acoustic measurements made on human cadaver ears, which indicate that perforation-induced changes in transmission result primarily from changes in driving pressure across the TM and that perforation-induced change in the structure of the TM and its coupling to the ossicles contributes a substantially smaller component. The model represents the effect of a perforation on the pressure difference across the TM by inclusion of a path for sound coupling through the perforation from the ear canal to the middle-ear cavity. The model implies that hearing loss with perforations depends primarily on three quantities: the perforation diameter, sound frequency, and the volume of air in the middle-ear cavity. For the conditions that produce the largest hearing loss ~low frequency and large perforation!, the model yields a simple dependence of loss on frequency, perforation diameter, and middle-ear cavity volume. Predictions from this model may be useful to clinicians in determining whether, in particular cases, hearing losses are explainable by the observed perforations or if additional pathology must be involved

Non-Ossicular Signal Transmission in Human Middle Ears: Experimental Assessment of the Acoustic Route with Perforated Tympanic Membranes

Direct acoustic stimulation of the cochlea by the sound-pressure difference between the oval and round windows (called the acoustic route ) has been thought to contribute to hearing in some pathological conditions, along with the normally dominant ossicular route. To determine the efficacy of this acoustic route and its constituent mechanisms in human ears, sound pressures were measured at three locations in cadaveric temporal bones [with intact and perforated tympanic membranes (TMs)]: (1) in the external ear canal lateral to the TM, PTM; (2) in the tympanic cavity lateral to the oval window, POW; and (3) near the round window, PRW. Sound transmission via the acoustic route is described by two concatenated processes: (1) coupling of sound pressure from ear canal to middle-ear cavity, H PCAV ≡ PCAV PTM, where PCAV represents the middle-ear cavity pressure, and (2) sound-pressure difference between the windows, HWPD ≡ (POW - PRW) PCAV. Results show that: H PCAV depends on perforation size but not perforation location; HWPD depends on neither perforation size nor location. The results (1) provide a description of the window pressures based on measurements, (2) refute the common otological view that TM perforation location affects the relative phase of the pressures at the oval and round windows, and (3) show with an intact ossicular chain that acoustic-route transmission is substantially below ossicular-route transmission except for low frequencies with large perforations. Thus, hearing loss from TM perforations results primarily from reduction in sound coupling via the ossicular route. Some features of the frequency dependence of H PCAV and HWPD can be interpreted in terms of a structure-based lumped-element acoustic model of the perforation and middle-ear cavities

Middle-Ear Function with Tympanic-Membrane Perforations. I. Measurements and Mechanisms

Sound transmission through ears with tympanic-membrane ~TM! perforations is not well understood. Here, measurements on human-cadaver ears are reported that describe sound transmission through the middle ear with experimentally produced perforations, which range from 0.5 to 5.0 mm in diameter. Three response variables were measured with acoustic stimulation at the TM: stapes velocity, middle-ear cavity sound pressure, and acoustic impedance at the TM. The stapes-velocity measurements show that perforations cause frequency-dependent losses; at low frequencies losses are largest and increase as perforation size increases. Measurements of middle-ear cavity pressure coupled with the stapes-velocity measurements indicate that the dominant mechanism for loss with TM perforations is reduction in pressure difference across the TM; changes in TM-to-ossicular coupling generally contribute less than 5 dB to the loss. Measurements of middle-ear input impedance indicate that for low frequencies, the input impedance with a perforation approximates the impedance of the middle-ear cavity; as the perforation size increases, the similarity to the cavity’s impedance extends to higher frequencies. The collection of results suggests that the effects of perforations can be represented by the path for air-volume flow from the ear canal to the middle-ear cavity. The quantitative description of perforation-induced losses may help clinicians determine, in an ear with a perforation, whether poor hearing results only from the perforation or whether other pathology should be expected

Selection of a network of large lakes and reservoirs suitable for global environmental change analysis using Earth Observation

The Globo Lakes project, a global observatory of lake responses to environmental change, aims to exploit current satellite missions and long remote-sensing archives to synoptically study multiple lake ecosystems, assess their current condition, reconstruct past trends to system trajectories, and assess lake sensitivity to multiple drivers of change. Here we describe the selection protocol for including lakes in the global observatory based upon remote-sensing techniques and an initial pool of the largest 3721 lakes and reservoirs in the world, as listed in the Global Lakes and Wetlands Database. An 18-year-long archive of satellite data was used to create spatial and temporal filters for the identification of water bodies that are appropriate for remote-sensing methods.Further criteria were applied and tested to ensure the candidate sites span a wide range of ecological settings and characteristics; a total 960 lakes, lagoons, and reservoirs were selected. The methodology proposed here is applicable to new generation satellites,such as the European Space Agency Sentinel-series

Lake surface temperature [in “State of the Climate in 2017”]

Observed lake surface water temperature anomalies in 2017 are placed in the context of the recent warming observed in global surface air temperature by collating long-term in situ lake surface temperature observations from some of the world’s best-studied lakes and a satellite-derived global lake surface water temperature dataset. The period 1996–2015, 20 years for which satellite-derived lake temperatures are available, is used as the base period for all lake temperature anomaly calculations

Sources of nonlinearities, chatter generation and suppression in metal cutting

The mechanics of chip formation has been revisited in order to understand functional relationships between the process and the technological parameters. This has led to the necessity of considering the chip-formation process as highly nonlinear, with complex interrelations between its dynamics and thermodynamics. In this paper a critical review of the state of the art of modelling and the experimental investigations is outlined with a view to how the nonlinear dynamics perception can help to capture the major phenomena causing instabilities (chatter) in machining operations. The paper is concluded with a case study, where stability of a milling process is investigated in detail, using an analytical model which results in an explicit relation for the stability limit. The model is very practical for the generation of the stability lobe diagrams, which is time consuming when using numerical methods. The extension of the model to the stability analysis of variable pitch cutting tools is also given. The application and verification of the method are demonstrated by several examples

The Context of Temporal Processing Is Represented in the Multidimensional Relationships between Timing Tasks

In the present study we determined the performance interrelations of ten different tasks that involved the processing of temporal intervals in the subsecond range, using multidimensional analyses. Twenty human subjects executed the following explicit timing tasks: interval categorization and discrimination (perceptual tasks), and single and multiple interval tapping (production tasks). In addition, the subjects performed a continuous circle-drawing task that has been considered an implicit timing paradigm, since time is an emergent property of the produced spatial trajectory. All tasks could be also classified as single or multiple interval paradigms. Auditory or visual markers were used to define the intervals. Performance variability, a measure that reflects the temporal and non-temporal processes for each task, was used to construct a dissimilarity matrix that quantifies the distances between pairs of tasks. Hierarchical clustering and multidimensional scaling were carried out on the dissimilarity matrix, and the results showed a prominent segregation of explicit and implicit timing tasks, and a clear grouping between single and multiple interval paradigms. In contrast, other variables such as the marker modality were not as crucial to explain the performance between tasks. Thus, using this methodology we revealed a probable functional arrangement of neural systems engaged during different timing behaviors