Discrete Mechanics Research Articles

Optimized flapping flight in Venus surface atmospheric conditions

Three recently approved space missions are headed towards Venus, to help answer major questions about Venus atmosphere and geology. However, many existing questions cannot be properly addressed without direct in situ measurements from Venus surface or within the atmosphere. To this end, flapping wing vehicle concept is selected, optimized for Venus atmospheric flight, and evaluated using energy efficiency as performance criteria. Flapping wing vehicle computational model is derived based on discrete variational mechanics and quasi-steady aerodynamics, with all relevant aerodynamic phenomena included. Flapping wing vehicle computational model is then embedded within optimization algorithm, which is utilized to obtain energy efficient flapping patterns for forward flight in Venus surface atmospheric conditions. Numerical optimization is performed for different neutrally buoyant configurations, with wingspan ranging from 10 mm to 1 m. Different forward velocities are used as well, where maximum velocity is limited by an advance ratio of 0.5. Bumblebee and hummingbird-sized vehicles, with a wingspan of 30 mm and 30 cm, are selected as the most representative test cases and thoroughly studied. It is proved that flapping wing propulsion is a feasible and effective concept for Venus exploration purposes. Finally, based on a comparison of the selected test cases, general conclusions are drawn on the flapping wing dynamics and flight mechanics in the Venus atmosphere. Significant difference in the propulsion mechanism has been observed, based on the aerial vehicle size. In order to maximize propulsive efficiency, the smaller vehicle mostly exploited aerodynamic forces related to the leading edge vortex, while the larger vehicle relied more on added mass and rotational forces.

Sexually dimorphic associations between prenatal blood lead exposure and performance on a behavioral testing battery in children

BackgroundAssociations between lead (Pb) and neurodevelopment have been studied widely in the context of global measures of cognitive function, such as IQ. Operant test batteries consist of behavioral tasks that can be used to target discrete cognitive and behavioral mechanisms, which contribute to global cognitive faculties. ObjectivesThe goals of this study were to identify Pb-associated deficits in cognitive development and determine the underlying mechanisms involved, utilizing an operant test battery. We evaluated effect modification by child sex. MethodsThis study utilized data from a prospective cohort in Mexico City. We included 549 participants aged 6-to-7 years with complete data on prenatal blood Pb measurements, Operant Test Battery (OTB) tasks, and demographic covariates. General linear models were used to examine the association of Pb levels at each prenatal timepoint and OTB performance. Effect modification by child sex was evaluated using 2-way interaction terms. ResultsIn three of the operant tasks, we observed that higher late-pregnancy blood Pb concentrations were associated with greater response latencies. In the temporal processing task, we observed that higher late-pregnancy Pb exposure was associated with worse overall task performance. Further, in two operant tasks, the effects of Pb were dependent on the sex of the child, such that the effects of Pb were more pronounced in females in the condition position responding task, but stronger in males in the temporal processing task. ConclusionsOur results suggest that prenatal Pb concentrations yield broad dysregulation of executive functions, which can be attributed to dysregulation of temporal processing. In addition, we observed sex differences in two operant tasks suggesting that some Pb effects on neurocognitive function may be sexually dimorphic.

The relationship between adverse childhood experiences, the frequency and acuity of emergency department utilization and primary care engagement

IntroductionA history of adverse child experiences (ACEs) is associated with increased high-risk adult behaviors, morbidity, mortality, and use of the emergency department. This study was designed to understand the relationship between ACEs and the characteristics of emergency department use and primary care engagement. MethodsAn in-person survey was conducted at an academic emergency department (ED) assessing ACE score, emergency department utilization and acuity, and primary care engagement. ResultsThe prevalence of ACEs was 71.1% with 1+ ACE and 32.5% with 4+ ACE. ACE scores of four or more were associated with three or more ED visits in the past year compared those with an ACE score of zero (OR 3.22; p < 0.05) and when adjusted for sociodemographic factors (OR 3.22; p < 0.10). Higher ACE scores were associated with lower acuity presentations as indicated by the Emergency Severity Index before (ACE score 1 OR 3.91 p < 0.05; ACE score 2–3 OR 2.35 p < 0.05; ACE score 4+ OR 3.95 p < 0.05) and after adjustment (ACE score 1 OR 3.80 p < 0.10; ACE 2–3 OR 3.50 p < 0.10; ACE 4+ OR 4.36 p < 0.05). There was no association between ACE score and having a primary care provider (PCP), frequency of PCP visits, or PCP rating. ConclusionHigher ACE scores were associated with higher emergency department utilization and lower acuity presentations but not associated with levels of primary care engagement. Additional investigations are needed to adequately characterize the discrete causal mechanisms behind these current findings.

From cradle to grave: neurogenesis, neuroregeneration and neurodegeneration in Alzheimer's and Parkinson's diseases.

Two of the most common neurodegenerative disorders – Alzheimer’s and Parkinson’s diseases – are characterized by synaptic dysfunction and degeneration that culminate in neuronal loss due to abnormal protein accumulation. The intracellular aggregation of hyper-phosphorylated tau and the extracellular aggregation of amyloid beta plaques form the basis of Alzheimer’s disease pathology. The major hallmark of Parkinson’s disease is the loss of dopaminergic neurons in the substantia nigra pars compacta, following the formation of Lewy bodies, which consists primarily of alpha-synuclein aggregates. However, the discrete mechanisms that contribute to neurodegeneration in these disorders are still poorly understood. Both neuronal loss and impaired adult neurogenesis have been reported in animal models of these disorders. Yet these findings remain subject to frequent debate due to a lack of conclusive evidence in post mortem brain tissue from human patients. While some publications provide significant findings related to axonal regeneration in Alzheimer’s and Parkinson’s diseases, they also highlight the limitations and obstacles to the development of neuroregenerative therapies. In this review, we summarize in vitro and in vivo findings related to neurogenesis, neuroregeneration and neurodegeneration in the context of Alzheimer’s and Parkinson’s diseases.

Implications of nocebo in anaesthesia care.

Nocebo refers to non-pharmacological adverse effects of an intervention. Well-intended procedural warnings frequently function as a nocebo. Both nocebo and placebo are integral to the generation of 'real' treatment effects and their associated 'real' side-effects. They are induced or exacerbated by: context; negative expectancy; and negative conditioning surrounding treatment. Since the late 1990s, the neuroscience literature has repeatedly demonstrated that the nocebo effect is mediated by discrete neurobiological mechanisms and specific physiological modulations. Although no single biological mechanism has been found to explain the nocebo effect, nocebo hyperalgesia is thought to initiate from the dorsal lateral prefrontal cortex subsequently triggering the brain's descending pain modulatory system and other pain regulation pathways. Functional magnetic resonance imaging shows that expectation of increased pain is accompanied by increased neural activity in the hippocampus and midcingulate cortex which is not observed when analgesia is expected. Functional magnetic resonance imaging studies have shown that the anterior cingulate cortex is pivotal in the perception of affective pain evoked by nocebo words. Research has also explored neurotransmitters which mediate the nocebo effect. The neuropeptide cholecystokinin appears to play a key role in the modulation of pain by nocebo. Hyperalgesia generated by nocebo also increases the activity of the hypothalamic-pituitary-adrenal axis as indicated by increases in plasma cortisol. The avoidance or mitigation of nocebo needs to be recognised as a core clinical skill in optimising anaesthesia care. Embracing the evidence around nocebo will allow for phrases such as 'bee sting' and 'sharp scratch' to be thought of as clumsy verbal relics of the past. Anaesthesia as a profession has always prided itself on practicing evidence-based medicine, yet for decades anaesthetists and other healthcare staff have communicated in ways counter to the evidence. The premise of every interaction should be 'primum non nocere' (first, do no harm). Whether the context is research or clinical anaesthesia practice, the nocebo can be ignored no longer.

Unravelling the highly efficient synthesis of individual carbon nanodots from casein micelles and the origin of their competitive constant-blue-red wavelength shift luminescence mechanism for versatile applications.

Synthesis of casein-derived carbon nanodots (CND) using a microwave-assisted approach, giving a high product yield (25%), is reported. Casein was used as a sustainable carbon source, and polyvinylpyrrolidone was used as a stabilizer for the nanodots. The size of the prepared amorphous CND corresponds to individual casein coils, which were only partially carbonized. They were obtained due to the disintegration of casein micelles and submicelles within the microwave-assisted solvothermal process. The resulting nanodots had bright photoluminescence, and their electronic structure and optical properties were investigated. A novel competitive model of their luminescence mechanism was introduced to explain a phenomenon beyond the standard models. The synthesized carbon nanodots were used as luminescent ink for anticounterfeit applications. A polymer matrix nanocomposite was prepared by dispersing the nanodots in a flexible and robust poly(styrene-ethylene-butylene-styrene) tri-block copolymer (SEBS) using the solution cast method. For the first time, the effect of CND on the luminescence and mechanical properties of the SEBS/CND self-supporting films was studied. The film was also studied as a phosphor for light-emitting diodes, with a unique experimental setup to avoid self-absorption, which results in low efficiency and eliminates the excess UV transmitted. Because of their high luminescence, photostability, and mechanical properties, these CND could be used as luminescent labels in the packaging and optoelectronics industries.

Object Detection in Large-Scale Remote-Sensing Images Based on Time-Frequency Analysis and Feature Optimization

Recently, optical remote-sensing images have been steadily growing in size, as they contain massive data and complex backgrounds. This trend presents several problems for object detection, for example, increased computation time and memory consumption and more false positives due to the complex backgrounds of large-scale images. Inspired by deep neural networks combined with time-frequency analysis, we propose a time-frequency analysis-based object detection method for large-scale remote-sensing images with complex backgrounds. We utilize wavelet decomposition to carry out a time-frequency transform and then integrate it with deep learning in feature optimization. To effectively capture the time-frequency features, we propose a feature optimization method based on deep reinforcement learning to select the dominant time-frequency channels. Furthermore, we design a discrete wavelet multiscale attention mechanism (DW-MAM), enabling the detector to concentrate on the object area rather than the background. Extensive experiments show that the proposed method of learning from time-frequency channels not only solves the challenges of large-scale and complex backgrounds, but also improves the performance compared to the original state-of-the-art object detection methods. In addition, the proposed method can be used with almost all object detection neural networks, regardless of whether they are anchor-based or anchor-free detectors, horizontal or rotation detectors.

Dynamic output feedback control for networked control systems: A sum-based discrete event-triggered approach

This paper investigates the event-based dynamic output feedback control for networked control system with actuator failures. A novel sum-based discrete event-triggered mechanism (SDETM) is proposed, whose triggering condition includes not only the current sample of system states but also previous samples. With the proposed SDETM, a dynamic output feedback controller (DOFC) is developed under a general networked control system (NCS) structure. We consider a general system structure where two network channels are involved, and the proposed SDETM is employed to both networks to extensively save network resources. A novel stability criteria is established for the closed-loop system based on the Lyapunov-Krasovskii functional method. By using the Cone-complimentarity Linearization (CCL) approach, sufficient conditions are derived to co-design the DOFC and triggering parameters. The effectiveness and advantage of the proposed method is verified by a satellite control system.

A sum-based discrete event-triggered dynamic output feedback control for interval type-2 fuzzy systems

The current study concentrates on the event-based controller design for nonlinear networked systems characterized by the interval type-2 (IT2) fuzzy model. An innovative sum-based discrete event-triggered mechanism (SDETM), whose triggering condition includes several previous measurement samples, is proposed. Compared to the traditional event-triggered mechanism (ETM), the novel SDETM requires less network resources consumption. A dynamic output feedback controller (DOFC) is designed to achieve stability of the system. A novel stability criteria is established via the Lyapunov–Krasovskii functional method with the prescribed H∞ performance. Co-design of the DOFC and SDETM parameters is carried out using the cone complimentarity linearization (CCL) algorithm. The effectiveness of the proposed method is demonstrated with two practical cases.

Phosphoproteomic responses of TORC1 target kinases reveal discrete and convergent mechanisms that orchestrate the quiescence program in yeast.

The eukaryotic TORC1 kinase assimilates diverse environmental cues, including growth factors and nutrients, to control growth by tuning anabolic and catabolic processes. In yeast, TORC1 stimulates protein synthesis in response to abundant nutrients primarily through its proximal effector kinase Sch9. Conversely, TORC1 inhibition following nutrient limitation unlocks various distally controlled kinases (e.g., Atg1, Gcn2, Npr1, Rim15, Slt2/Mpk1, and Yak1), which cooperate through poorly defined circuits to orchestrate the quiescence program. To better define the signaling landscape of the latter kinases, we use invivo quantitative phosphoproteomics. Through pinpointing known and uncharted Npr1, Rim15, Slt2/Mpk1, and Yak1 effectors, our study examines the architecture of the distally controlled TORC1 kinase network. Accordingly, this is built on a combination of discrete, convergent, and multilayered feedback regulatory mechanisms, which likely ensure homeostatic control of and/or robust responses by TORC1 and its effector kinases under fluctuating nutritional conditions.

Emerging trends of therapy related myeloid neoplasms following modern cancer therapeutics in the United States

Clonal hematopoiesis (CH) is a risk factor for the development of therapy-related myelodysplastic syndromes (tMDS) and acute myeloid leukemia (tAML). Adoption of targeted-immunotherapeutics since 2011, may alter the risk of CH progression to tMDS/AML. To study this, we evaluated risk of tMDS and tAML in 667 588 ≥ 1-year survivors of non-small cell lung cancer (NSCLC), renal cell carcinoma (RCC), melanoma and multiple-myeloma (MM) diagnosed during: 2000–2005, 2006–2010 and 2011–2016. The risk of tMDS increased significantly after NSCLC across all time periods (Ptrend = 0.002) while tAML risk decreased from 2006–2010 to 2011–2016, coinciding with increasing use of non-chemotherapeutic agents. tAML risk after RCC decreased (Ptrend = 0.007) whereas tMDS risk did not significantly change over time. After melanoma, tMDS and tAML risks were similar to the general population. tMDS and tAML risk after MM increased from the first to second time-period, however, only risk of tMDS decreased during last period. We report diverging trends in the risk of tAML and tMDS after adoption of modern cancer therapies for specific cancers. It is imperative to further explore impact of contemporary treatment strategies on clonal evolution. Modern treatments via their discrete mechanism of actions on pre-existing CH may alter the risk of subsequent tMDS and tAML.

Discrete phase space and continuous time relativistic quantum mechanics II: Peano circles, hyper-tori phase cells, and fiber bundles

The discrete phase space and continuous time representation of relativistic quantum mechanics are further investigated here as a continuation of paper I.1 The main mathematical construct used here will be that of an area filling Peano curve. We show that the limit of a sequence of a class of Peano curves is a Peano circle denoted as [Formula: see text], a circle of radius [Formula: see text] where [Formula: see text]. We interpret this two-dimensional (2D) Peano circle in our framework as a phase cell inside our 2D discrete phase plane. We postulate that a first quantized Planck oscillator, being very light, and small beyond current experimental detection, occupies this phase cell [Formula: see text]. The time evolution of this Peano circle sweeps out a 2D vertical cylinder analogous to the worldsheet of string theory. Extending this to 3D space, we introduce a [Formula: see text]-dimensional phase space hyper-tori [Formula: see text] as the appropriate phase cell in the physical dimensional discrete phase space. A geometric interpretation of this structure in state space is given in terms of product fiber bundles. We also study free scalar Bosons in the background [Formula: see text]-dimensional discrete phase space and continuous time state space using the relativistic partial difference-differential Klein–Gordon equation. The second quantized field quanta of this system can cohabit with the tiny Planck oscillators inside the [Formula: see text] phase cells for eternity. Finally, a generalized free second quantized Klein–Gordon equation in a higher [Formula: see text]-dimensional discrete state space is explored. The resulting discrete phase space dimension is compared to the significant spatial dimensions of some of the popular models of string theory.

Physically-based structural modeling of a typical regenerative tissue analog bridges material macroscale continuum and cellular microscale discreteness and elucidates the hierarchical characteristics of cell-matrix interaction

This paper presents a comprehensive physically-based structural modelling for the passive and active biomechanical processes in a typical engineered tissue – namely, cell-compacted collagen gel. First, it introduces a sinusoidal curve analog for quantifying the mechanical response of the collagen fibrils and a probability distribution function of the characteristic crimp ratio for taking into account the fibrillar geometric entropic effect. The constitutive framework based on these structural characteristics precisely reproduces the nonlinearity, the viscoelasticity, and fairly captures the Poisson effect exhibiting in the macroscale tensile tests; which, therefore, substantially validates the structural modelling for the analysis of the cell-gel interaction during collagen gel compaction. Second, a deterministic molecular clutch model specific to the interaction between the cell pseudopodium and the collagen network is developed, which emphasizes the dependence of traction force on clutch number altering with the retrograde flow velocity, actin polymeric velocity, and the deformation of the stretched fibril. The modelling reveals the hierarchical features of cellular substrate sensing, i.e. a biphasic traction force response to substrate elasticity begins at the level of individual fibrils and develops into the second biphasic sensing by means of the fibrillar number integration at the whole-cell level. Singular in crossing the realms of continuum and discrete mechanics, the methodologies developed in this study for modelling the filamentous materials and cell-fibril interaction deliver deep insight into the temporospatially dynamic 3D cell-matrix interaction, and are able to bridge the cellular microscale and material macroscale in the exploration of related topics in mechanobiology.

An alternative to the concept of continuous medium

Discrete mechanics proposes an alternative formulation of the equations of mechanics where the Navier-Stokes and Navier-Lam\'e equations become approximations of the equation of discrete motion. It unifies the fields of fluid and solid mechanics by extending the fields of application of these equations to all space and time scales. This article presents the essential differences induced by the abandonment of the notion of continuous medium and global frame of reference. The results of the mechanics of continuous medium validated by fluid and solid observations are not questioned. The concept of continuous medium is not invalidated, the discrete formulation proposed simply widens the spectrum of the applications of the classical equations. The discrete equation of motion introduces several important modifications, in particular the fundamental law of the dynamics on an element of volume becomes a law of conservation of the accelerations on an edge. The acceleration considered as an absolute quantity is written as a sum of two components, one soledoidal the other irrotational according to a local orthogonal Helmholtz-Hodge decomposition. The mass is abandoned and replaced by the compression and rotation energies represented by the scalar and vectorial potentials of the acceleration. The equation of motion and all the physical parameters are expressed only with two fundamental units, those of length and time. The essential differences between the two approaches are listed and some of them are discussed in depth. This is particularly the case with the known paradoxes of the Navier-Stokes equation or the importance of inertia for the Navier-Lam\'e equation.

Factors Associated with Fatality in Ontario Thoroughbred Racehorses: 2003-2015.

Simple SummaryOntario’s Alcohol and Gaming Commission records equine racing fatalities through its Equine Health Program. This study examines the 695 Thoroughbred occurrences from 2003 to 2015 with the aim of identifying associations. Deaths occurred within 60 days of a horse racing or being entered or qualified to race. Calculated on the most commonly adopted basis, rates for Ontario Thoroughbreds are high—2.94/1000 starts (all fatalities) and 1.96/1000 (breakdowns only), compared with a global industry breakdown range of 0.29–2.36/1000 starts. The study revealed several significant risk factors, including workload, stage of training, age, sex, stage of career, finish position, race field size, and day of week. Among fatalities were groups where combinations of these risk factors were important, such as being a two-year-old male, un-castrated, and in early training. Probability of fatality fell over the study period in response to increasing awareness through existence of the Program and adoption of new regulations, but remains of concern. All identified associations represent aspects of management and industry structure that are amenable to change with a view to reducing fatalities. A link between fatality and cumulative, non-fatal outcomes should also be considered. An overall approach might view associated factors as sources of physical and psychological stress that, acutely and cumulatively, may influence the liability for adverse outcomes in training and racing.Ontario’s Alcohol and Gaming Commission records equine racing fatalities through its Equine Health Program. The present study examined all Thoroughbred fatalities from 2003 to 2015, inclusive, to identify associations. Official records and details of fatalities were combined in multivariable logistic regression modelling of 236,386 race work-events (433 fatalities), and 459,013 workout work-events (252 fatalities). Fatality rates were 2.94/1000 race starts (all fatalities) and 1.96/1000 (breakdowns only) with an overall rate of 2.61% or 26.1 fatalities/1000 horses. Comparison with published reports reveals rates to be high. Musculoskeletal injury was the predominant complaint and there was a high incidence of horses dying suddenly. Liability was high for young horses early in the season with a differential according to sex and whether a male horse was gelded. Horses undertaking repeated workouts had a higher liability and liability was higher in workouts for horses switching from dirt/synthetic to turf racing and for young horses in sprints. Race distance was not significant but high fatality rates in some large field, distance races combined with effects of age and workload identified groups at particular risk. As field size increased, fatality liability increased for early-finishing horses. Findings suggest jockey strategy could be an important factor influencing fatalities. Probability of fatality declined over the study period. Findings indicate that rapid accumulation of workload in animals early in their preparation is likely to be damaging. Fatality fell toward the end of a season and for horses with a long career history of successful performance; however, horses not exhibiting this robustness and staying power represent the population of greatest concern. Associations may be characterised as representing sources of stress, current or cumulative, and identifying at-risk animals on this basis may be as productive as targeting specific, discrete mechanisms suspected to contribute to individual fatalities.

Regional variations in discrete collagen fibre mechanics within intact intervertebral disc resolved using synchrotron computed tomography and digital volume correlation

Many soft tissues, such as the intervertebral disc (IVD), have a hierarchical fibrous composite structure which suffers from regional damage. We hypothesise that these tissue regions have distinct, inherent fibre structure and structural response upon loading. Here we used synchrotron computed tomography (sCT) to resolve collagen fibre bundles (∼5μm width) in 3D throughout an intact native rat lumbar IVD under increasing compressive load. Using intact samples meant that tissue boundaries (such as endplate-disc or nucleus-annulus) and residual strain were preserved; this is vital for characterising both the inherent structure and structural changes upon loading in tissue regions functioning in a near-native environment. Nano-scale displacement measurements along >10,000 individual fibres were tracked, and fibre orientation, curvature and strain changes were compared between the posterior-lateral region and the anterior region. These methods can be widely applied to other soft tissues, to identify fibre structures which cause tissue regions to be more susceptible to injury and degeneration. Our results demonstrate for the first time that highly-localised changes in fibre orientation, curvature and strain indicate differences in regional strain transfer and mechanical function (e.g. tissue compliance). This included decreased fibre reorientation at higher loads, specific tissue morphology which reduced capacity for flexibility and high strain at the disc-endplate boundary. Statement of significanceThe analyses presented here are applicable to many collagenous soft tissues which suffer from regional damage. We aimed to investigate regional intervertebral disc (IVD) structural and functional differences by characterising collagen fibre architecture and linking specific fibre- and tissue-level deformation behaviours. Synchrotron CT provided the first demonstration of tracking discrete fibres in 3D within an intact IVD. Detailed analysis of regions was performed using over 200k points, spaced every 8 μm along 10k individual fibres. Such comprehensive structural characterisation is significant in informing future computational models. Morphological indicators of tissue compliance (change in fibre curvature and orientation) and fibre strain measurements revealed localised and regional differences in tissue behaviour.

Insights from the MEDE program: An overview of microstructure–property linkages in the dynamic behaviors of magnesium alloys

Magnesium (Mg) and its alloys have been the subject of intensive scientific research and development in the communities of materials science and engineering, mechanical engineering and manufacturing. Considering their light weight and high specific strength, current and potential applications include the aerospace industry, automobiles, and vehicle and personnel armors. This range of applications demands a good understanding of the behavior under extreme conditions such as impact or high strain rate loading. The past two decades have witnessed a surge of studies of the mechanical responses of Mg and its alloys under impact loading, both experimentally and using simulations and modeling at different spatial and temporal scales. Experimental examinations at strain rates up to 107 s−1 (shock wave loading) have been published. In terms of simulations and modeling efforts, multi-physics, multi-scale investigations, from first principles calculations (density functional theory, DFT), molecular dynamics (MD), discrete dislocation dynamics (DDD), crystal plasticity (CP) and continuum mechanics have all been explored. To address the challenges in design, manufacturing and application of Mg alloys, the US Army Research Laboratory (US-ARL) created the Materials in Extreme Dynamic Environments (MEDE) Collaborative Research Alliance (CRA) in 2012. The goal of the Metals Program within the MEDE CRA has been to observe, understand, and design the mechanisms active within Mg and Mg alloys in these extreme conditions.In this paper, fundamental aspects of plastic deformation of Mg and Mg-alloys and the history of the research efforts in experiments, modeling, and simulations available in the literature are critically reviewed. Key findings and contributions from the Materials in Extreme Dynamic Environments (MEDE) Metals Collaborative Materials Research Group (CMRG) are presented, followed by summary and future perspectives.

A distinct association of inflammatory molecules with outcomes of COVID-19 in younger versus older adults

Aging can alter immunity affecting host defense. COVID-19 has the most devastating clinical outcomes in older adults, raising the implication of immune aging in determining its severity and mortality. We investigated biological predictors for clinical outcomes in a dataset of 13,642 ambulatory and hospitalized adult COVID-19 patients, including younger (age < 65, n = 566) and older (age ≥ 65, n = 717) subjects, with in-depth analyses of inflammatory molecules, cytokines and comorbidities. Disease severity and mortality in younger and older adults were associated with discrete immune mechanisms, including predominant T cell activation in younger adults, as measured by increased soluble IL-2 receptor alpha, and increased IL-10 in older adults although both groups also had shared inflammatory processes, including acute phase reactants, contributing to clinical outcomes. These observations suggest that progression to severe disease and death in COVID-19 may proceed by different immunologic mechanisms in younger versus older subjects and introduce the possibility of age-based immune directed therapies.

Optimal control simulations of two-finger grasps

Grasping is a complex human activity performed with readiness through a complicated mechanical system as an end effector, i.e. the human hand. Here, we apply a direct transcription method of discrete mechanics and optimal control with constraints (DMOCC) to reproduce human-level grasping of an object with a three-dimensional model of the hand, actuated through joint control torques. The equations of motions describing the hand dynamics are derived from a discrete variational principle based on a discrete action functional, which gives the time integrator structure-preserving properties. The grasping action is achieved through a series of constraints, which generate a hybrid dynamical system with a given switching sequence and unknown switching times. To determine a favourable trajectory for grasping action, we solve an optimal control problem (OCP) with different physiological objectives subject to discrete Euler–Lagrange equations, boundary conditions and path constraints.

The Adipokine Component in the Molecular Regulation of Cancer Cell Survival, Proliferation and Metastasis

A hormonal imbalance may disrupt the rigorously monitored cellular microenvironment by hampering the natural homeostatic mechanisms. The most common example of such hormonal glitch could be seen in obesity where the uprise in adipokine levels is in virtue of the expanding bulk of adipose tissue. Such aberrant endocrine signaling disrupts the regulation of cellular fate, rendering the cells to live in a tumor supportive microenvironment. Previously, it was believed that the adipokines support cancer proliferation and metastasis with no direct involvement in neoplastic transformations and tumorigenesis. However, the recent studies have reported discrete mechanisms that establish the direct involvement of adipokine signaling in tumorigenesis. Moreover, the individual adipokine profile of the patients has never been considered in the prognosis and staging of the disease. Hence, the present manuscript has focused on the reported extensive mechanisms that culminate the basis of poor prognosis and diminished survival rate in obese cancer patients.