Adaptive Redistribution Research Articles

PD-1/CD80+ small extracellular vesicles from immunocytes induce cold tumours featured with enhanced adaptive immunosuppression

Only a minority of cancer patients benefit from immune checkpoint blockade therapy. Sophisticated cross-talk among different immune checkpoint pathways as well as interaction pattern of immune checkpoint molecules carried on circulating small extracellular vesicles (sEV) might contribute to the low response rate. Here we demonstrate that PD-1 and CD80 carried on immunocyte-derived sEVs (I-sEV) induce an adaptive redistribution of PD-L1 in tumour cells. The resulting decreased cell membrane PD-L1 expression and increased sEV PD-L1 secretion into the circulation contribute to systemic immunosuppression. PD-1/CD80+ I-sEVs also induce downregulation of adhesion- and antigen presentation-related molecules on tumour cells and impaired immune cell infiltration, thereby converting tumours to an immunologically cold phenotype. Moreover, synchronous analysis of multiple checkpoint molecules, including PD-1, CD80 and PD-L1, on circulating sEVs distinguishes clinical responders from those patients who poorly respond to anti-PD-1 treatment. Altogether, our study shows that sEVs carry multiple inhibitory immune checkpoints proteins, which form a potentially targetable adaptive loop to suppress antitumour immunity.

Adaptive Capacity Task Offloading in Multi-Hop D2D-Based Social Industrial IoT

Traditional communication technologies such as cellular networks are facing problems to support high service quality when used for time-critical applications in an Industrial Internet-of-Things (IIoT) context, including real-time data transmission, route dependability, and scalability. To address these problems, device-to-device (D2D) communications based on social relationships can be used, which allow for task-offloading: resource-rich devices share unused computing resources with resource constraint devices. However, unbalanced task offloading in Social IIoT (SIIoT) might actually degrade the overall system performance, which is not desirable. In this paper, we propose an adaptive capacity task offloading solution for D2D-based social industrial IoT (ToSIIoT) which considers devices utilization ratio and strength of social relationships in order to improve resource utilization, increase QoS and achieve better task completion rate. The proposed approach consists of three aspects: social-aware relay selection in a multi-hop D2D communication context, choice of a resource-rich SIIoT device for task offloading, and adaptive redistribution of tasks. The paper proposes heuristic algorithms, as finding optimal solutions to the problems are NP-hard. Extensive experimental results show that the proposed ToSIIoT performs better than existing approaches in terms of utilization ratio, QoS violation, average execution delay, and task completion ratio.

LOCOMOTOR KINETICS OF THE LOWER EXTREMITIES IN HEALTHY INDIVIDUALS AND IDIOPATHIC SCOLIOSIS

Aim: The definition of «muscle contractile reserve» is a prognostic criterion in assessing locomotor capabilities. Material and methods: Groups of adolescents: 1-healthy, 2-idiopathic scoliosis. Research methods: dynamometry, 3D video analysis of gait. Results: In AIS, the relative isometric moment of force is reduced compared to healthy ones: in hip extensors by 36% (p=0.00106), hip flexors by 33% (p=0.0002), hip abductors by 38% (p=0003), leg extensors by 37% (p=3.22E-07), leg flexors by 42% (p=4.15E-06). In healthy adolescents, the muscle reserve at a walking speed of 3.7-4.3 km/h was: in hip extensors and flexors 65-75%, hip adductors 30-40%, hip abductors — 80-90%, leg extensors — 70-80%, leg flexors — 80-90% and dorsal foot flexors — 75-90%. The kinetic values of the plantar flexors exceed the isometric maximum when the foot is placed at an angle of 90° by 30-40%. In AIS the distal muscle groups had no signs of functional damage; proximal muscle groups showed asymmetry (up to 25%) and a decrease in strength in the isometric mode by 33-42%. Muscle reserve at the same speed is reduced for anti-gravity muscles in AIS: in hip extensors by 40% and in leg extensors by 70%. The total joints power did not significantly differ from the control group. Conclusions: In locomotor stereotypes in patients with scoliosis, there was a pattern of adaptive redistribution of the kinetic potential of the contractile function from one joint muscle to another.

Оценка результатов внедрения гибридных моделей развития сферы социальных услуг в регионах России

In order to overcome the uneven consumption of social services and eliminate social development imbalances, Russian regions require measures to increase the output of such services with the existing resource base. To this end, the present study built a correlation model of the output indicator and parameters of the development intensity for regions characterised by hybrid models of social services. Data on state orders to private producers of social services, data on funds allocated for investment in fixed assets, including public-private partnership infrastructure projects, and data on grant funds directed to socially-oriented non-profit organisations for the period 2013-2020 were analysed. The obtained results show that adaptive redistribution of resources within hybrid models positively correlates with the output in most regions. Thus, a unidirectional positive relationship between changes in the sum of state orders to private producers and total output is characteristic for 34 Russian regions. A positive correlation between the output of social services and public-private partnership investment is observed in 64 regions. Grant support to socially-oriented non-profit organisations positively affects the output in most regions; this impact is significant for 51 regions. Simultaneously, the possibility of obtaining government funds by private producers is crucial for ensuring the growth of the output of social services. These findings largely contradict the original goal of developing a hybrid model, which is to attract private capital to the social sector in order to reduce budget expenditures for social services. The feasibility of the hybrid model, considering the provision of private participants with government funds, should be examined directly at the regional level.

Adaptive Redistribution and Replication to Improve the Responsiveness of Mobile Web Apps

In a mobile web app, a browser-based client communicates with a cloud-based server across the network. An app is statically divided into client and server functionalities, so the resulting division remains fixed at runtime. However, if such static division mismatches the current network conditions and the device’s processing capacities, app responsiveness and energy efficiency can deteriorate rapidly. To address this problem, we present Communicating Web Vessels (CWV), an adaptive redistribution and replication framework that improves the responsiveness of full-stack JavaScript mobile apps. Unlike standard computation offloading, in which client functionalities move to run on the server, CWV’s redistribution is bidirectional. Without any preprocessing, CWV enables apps to move any functionality from the server to the client and vice versa at runtime, thus adapting to the ever-changing execution environment of the web. Having moved to the client, former server functionalities become regular local functions. To further improve performance, CWV can replicate server-side functionalities on the client and keep the replicas consistent. By monitoring the network, CWV determines if a redistribution or a replication would improve app performance, and then analyzes, transforms, sandboxes, moves, or replicates functions and program state at runtime. An evaluation with third-party mobile web apps shows that CWV optimizes their performance for dissimilar network conditions and client devices. As compared to their original versions, CWV-powered web apps improve their performance (i.e., latency, energy consumption), particularly when executed over limited networks.1

Algorithm of anti-lock braking system for two-axle vehicles with one driving axle with adaptive redistribution of braking forces

The main purpose of active vehicle safety systems is to prevent an emergency situation. If such a situation arises, the system independently (without the participation of the driver) assesses the probable danger and, if necessary, prevents it by actively intervening in the driving process. One of the ways to increase the active safety of vehicles when braking is the use of anti-lock braking systems (ABS). The main problems in ensuring the operation of the ABS, built on different control principles and with different control parameters, are the impossibility of directly determining the vehicle speed and, as a result, the slip coefficient, as well as the inability to effectively respond to changing road conditions during braking. For example, when braking on a slippery supporting surface and trying to avoid an obstacle in front, there is a risk of losing traction and skidding. The algorithms of the ABS operation developed at present do not ensure the prevention of the occurrence and development of skidding under the conditions indicated above. The aim of the work is to increase the stability and controllability of two-axle vehicles with one driving axle during braking due to the adaptive redistribution of braking forces on the wheels. An algorithm for the operation of an anti-lock braking system with adaptive redistribution of braking forces on the wheels of a vehicle is proposed. Thanks to this algorithm, when braking on a slippery surface of a two-axle vehicle with one driving axle, the absence of wheel blocking and also skid resistance are ensured. The efficiency and effectiveness of the proposed algorithm when braking a two-axle vehicle with one driving axle on a slippery supporting surface were proved by the methods of simulation.

Investigation of human thermal comfort and improvement in public places adapted to a hot climate in Iraq

This study focuses on improving the thermal comfort in Mosques in Iraq. Omar bin Abdul Aziz Mosque in Baghdad is taken as a case study. In general, the weather in Baghdad is hot- dry climate during the summer. the study was conducted at the time of noon prayer on Friday where the maximum number of people can be obtained inside the Mosque about 500 worshipers and severe environmental conditions. Numerical methods (CFD) are used for the simulation utilizing the package of ANSYS (FLUENT V. 18). As the results depending on the number of elements, 4 millions elements are used for dividing the physical domain. Thermal comfort was assessed by finding the values of the predicted mean vote (PMV), predicted percentage of dissatisfied (PPD), and ASHRAE standard-55. The adaptive redistribution of the air conditioning device strategy at five cases is used to obtain the best thermal comfort. Moreover, changing the angle of air intake of space by changing the angle inclination of the access blade at three different angles of 0o, 7.5o and 15o degree, and studying its effect on the thermal comfort in breathing level. The four case is the best in terms of thermal comfort when the angle of intake air at 0o.when the PMV was 0.35 and PPD is 7.5, which is lower than the original state. The improving percentage of PPD is 10 % and PMV 14 %.

Differential regulation of vacuolar H+‐ATPase subunits by Transforming Growth Factor beta 1 (TGF‐β1) in salivary ducts

Bicarbonate concentration in saliva is controlled by the action of acid‐base transporters in salivary duct cells. We have previously shown expression of ATP6V1E1 and ATP6V1A in human and rodent salivary ducts and adaptive redistribution to the apical plasma membrane following acute and chronic metabolic acidosis. However, whether such redistribution has any physiological significance has not been elucidated. Using the human submandibular gland cell line HSG, we show for the first time functional expression of V‐ATPase in submandibular duct cells and introduce Transforming Growth Factor beta (TGF‐β) as a novel regulator of V‐ATPase subunits. Using QRT‐PCR, immunoblotting, biotinylation of surface proteins, immunofluorescence, and intracellular H(+) recording with H(+) ‐sensitive dye 2′,7′‐bis‐(carboxyethyl)‐5‐(and‐6)‐carboxyfluorescein, we show that activation of TGF‐β signalling upregulates ATP6V1E1 and ATP6V1B2, and has no effect on ATP6V1A. Following acidosis, neutralization of TGF‐βs or blocking of Smad2/3 phosphorylation decreased membrane expression of ATP6V1A, and prevented the acidosis‐induced increased V‐ATPase activity. The results suggest multiple modes of action of TGF‐β1 on V‐ATPase subunits in HSG cells: TGF‐β1 may regulate transcription or protein synthesis of certain subunits and trafficking of other subunits in a context‐dependent manner. Moreover, V‐ATPase is active in salivary duct cells and involved in intracellular pH regulation following acidosis.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Applications of combined financial strategies based on universal adaptive forecasting

We consider an online adaptive forecasting algorithm for time series elements. Based on this algorithm, we define a universal strategy for the financial market: such a strategy ensures asymptotically maximal profit compared to any trading strategy where decisions are made based on rules that depend continuously on the input information. To reduce risk, in simultaneous trading of several financial instruments we perform adaptive redistribution of the current capital among them according to the AdaHedge algorithm. We propose variations of a combined game with various algorithmic trading strategies. We give results of numerical experiments based on historical data of the MICEX and BATS (US) trading platforms.

Shrub cover expressed as an ‘arthropod island’ in xeric environments

Based on the vague importance of shrub cover, an attempt was made to create a theoretical concept framework known as an ‘arthropod-island’ analytical model. These models were based on the multi-bond correlation between shrubs, soil properties, and above- and below-ground biotic communities. By utilizing published datasets on (i.e., above- and below-ground) arthropod communities related to shrub species and age, the proposed models for an ‘arthropod island’ were applied in order to determine their fitness for xeric ecosystems. It was found that the ‘arthropod-island’ concept could be the result of statistical differences in ecologically adaptive (i.e., preferable) redistribution of arthropods among the microhabitats beneath the shrub canopy and in the open spaces. Taxon density, relative to the richness and Shannon indices, was found to be more sensitive to the selected models. The relative interaction intensity index [RII = (A − B)/(A + B), A = shrub canopy value, B = intershrub value] was found to be more suitable for the ‘arthropod island’ at the community level. The relative neighbor effect [RNE = (B − A)/max(A, B)] and RII were found to be suitable at the population level, while the fitted model heavily depended on the variety of arthropod taxon. It was suggested that there were consistent ‘arthropod island’–shrub relationships between shrub species and between shrub ages in terms of arthropod density at the community level. The arthropod taxon was found to indicate an inconsistent ‘arthropod island’–shrub relationship between shrub species that differed from shrub ages at the population level.

Planning for the unexpected: The value of reserve capacity for public transport network robustness

Public transport networks (PTN) are subject to recurring service disruptions. Most studies of the robustness of PTN have focused on network topology and considered vulnerability in terms of connectivity reliability. While these studies provide insights on general design principles, there is lack of knowledge concerning the effectiveness of different strategies to reduce the impacts of disruptions. This paper proposes and demonstrates a methodology for evaluating the effectiveness of a strategic increase in capacity on alternative PTN links to mitigate the impact of unexpected network disruptions. The evaluation approach consists of two stages: identifying a set of important links and then for each identified important link, a set of capacity enhancement schemes is evaluated. The proposed method integrates stochastic supply and demand models, dynamic route choice and limited operational capacity. This dynamic agent-based modelling of network performance enables to capture cascading network effects as well as the adaptive redistribution of passenger flows. An application for the rapid PTN of Stockholm, Sweden, demonstrates how the proposed method could be applied to sequentially designed scenarios based on their performance indicators. The method presented in this paper could support policy makers and operators in prioritizing measures to increase network robustness by improving system capacity to absorb unexpected disruptions.

Design of an amplitude-bounded output feedback adaptive neural control with guaranteed componentwise performance

This paper proposes a methodology for the design of a mixed output feedback linear and adaptive neural controller that guarantees componentwise boundedness of the tracking error within an a priori specified compact polyhedron for an uncertain nonlinear system. The approach is based on the design of a robust invariant ellipsoidal set where the adaptive neural network (NN) control is modeled as an amplitude-bounded signal. A linear error observer is employed to recover the unmeasured states, and a linear gain controller is used to enforce the containment of the ellipsoidal set within the performance polyhedron. The analysis and design of the observer and linear controller is set up as an LMI problem. The linear observer/controller scheme is then augmented with a general adaptive NN element having the purpose of approximating and compensating for the unknown nonlinearities thus providing performance improvement. The only requirement for the adaptive control signals is that their amplitudes must be confined within pre-specified limits. For this purpose, a novel mechanism called adaptive control redistribution is introduced to manage the adaptive NN control confinement during the online operation. A numerical example is used to illustrate the design methodology.

Agricultural Adaptation to a Changing Climate: Economic and Environmental Implications Vary by U.S. Region

Global climate models predict increases over time in average temperature worldwide, with significant impacts on local patterns of temperature and precipitation. The extent to which such changes present a risk to food supplies, farmer livelihoods, and rural communities depends in part on the direction, magnitude, and rate of such changes, but equally importantly on the ability of the agricultural sector to adapt to changing patterns of yield and productivity, production cost, and resource availability. Study findings suggest that, while impacts are highly sensitive to uncertain climate projections, farmers have considerable fl exibility to adapt to changes in local weather, resource conditions, and price signals by adjusting crops, rotations, and production practices. Such adaptation, using existing crop production technologies, can partially mitigate the impacts of climate change on national agricultural markets. Adaptive redistribution of production, however, may have signifi cant implications for both regional land use and environmental quality.

Rab11b and its effector Rip11 regulate the acidosis‐induced traffic of V‐ATPase in salivary ducts

Redistribution of acid-base transporters is a crucial regulatory mechanism for many types of cells to cope with extracellular pH changes. In epithelial cells, however, translocation of acid-base transporters ultimately leads to changes in vectorial transport of H+ and HCO3-. We have previously shown that the bicarbonate-secreting epithelium of salivary ducts responds to changes of systemic acid-base balance by adaptive redistribution of H+ and HCO3- transporters, thereby influencing the ionic composition and buffering capacity of saliva. However, the specific proteins involved in regulated vesicular traffic of acid-base transporters are largely unknown. In the present study we have investigated the impact of Rab11 family members on the acidosis-induced trafficking of the vacuolar-type H+-ATPase (V-ATPase) in salivary duct cells in vitro using the human submandibular cell line of ductal origin HSG as an experimental model. The results show that Rab11b is expressed in salivary ducts and exhibits a significantly higher co-localization with V-ATPase than Rab11a and Rab25. We also show that Rab11 but not Rab25 interacts with the ε subunit of V-ATPase. Extracellular acidosis up-regulates Rab11b expression and protein abundance in HSG cells and causes translocation of the V-ATPase from intracellular pools toward the plasma membrane. Loss-of-function experiments using specific siRNA either against Rab11b or against its effector Rip11 prevent acidosis-induced V-ATPase translocation. These data introduce Rab11b as a crucial regulator and Rip11 as mediator of acidosis-induced V-ATPase traffic in duct cells of submandibular gland.

Female Scent Signals Enhance the Resistance of Male Mice to Influenza

BackgroundThe scent from receptive female mice functions as a signal, which stimulates male mice to search for potential mating partners. This searching behavior is coupled with infection risk due to sniffing both scent marks as well as nasal and anogenital areas of females, which harbor bacteria and viruses. Consideration of host evolution under unavoidable parasitic pressures, including helminthes, bacteria, viruses, etc., predicts adaptations that help protect hosts against the parasites associated with mating.Methods and FindingsWe propose that the perception of female signals by BALB/c male mice leads to adaptive redistribution of the immune defense directed to protection against respiratory infection risks. Our results demonstrate migration of macrophages and neutrophils to the upper airways upon exposure to female odor stimuli, which results in an increased resistance of the males to experimental influenza virus infection. This moderate leukocyte intervention had no negative effect on the aerobic performance in male mice.ConclusionsOur data provide the first demonstration of the adaptive immunological response to female odor stimuli through induction of nonspecific immune responses in the upper respiratory tract.

Surgical Stress-Induced Immune Cell Redistribution Profiles Predict Short-Term and Long-Term Postsurgical Recovery

The experience of undergoing surgery is known to induce a short-term, fight-or-flight physiological stress response. As an optimum immune response at the site of surgery would enhance tissue repair, we examined surgical stress-induced immune cell redistribution profiles as predictors, and potential mediators, of short and long-term postoperative recovery. We tested the a priori hypothesis that predefined adaptive immune cell redistribution profiles observed during surgery will predict enhanced postoperative recovery. This prospective longitudinal study involved fifty-seven patients undergoing meniscectomy. Knee function was assessed preoperatively and at one, three, eight, sixteen, twenty-four, and forty-eight weeks postoperatively with use of the clinically validated Lysholm scale, which assesses mechanical function, pain, mobility, and the ability to perform daily activities. Surgery-induced immune cell redistribution was measured in the blood at baseline, before surgery, and after surgery. Mixed-model repeated-measures analyses revealed a main effect of immune cell redistribution: patients who showed the predefined "adaptive" lymphocyte and monocyte redistribution profiles during surgery showed enhanced recovery. Interesting differences were also observed between the sexes: women as a group showed less adaptive redistribution and correspondingly showed significantly delayed maximum recovery, requiring forty-eight weeks, compared with men, who required only sixteen weeks. Inter-individual differences in leukocyte redistribution predicted the rate of recovery across both sexes. Immune cell redistribution that is induced by the stress of undergoing surgery can predict (and may partially mediate) postoperative healing and recovery. These findings may provide the basis for identifying patients (either prospectively or during surgery) who are likely to show good as opposed to poor recovery following surgery and for designing interventions that would maximize protective immune responses and enhance the rate and extent of recovery.

Recognition Versus Adaptive Up-regulation and Degradation of CC Chemokines by the Chemokine Decoy Receptor D6 Are Determined by Their N-terminal Sequence

The chemokine decoy receptor D6 controls inflammatory responses by selective recognition and degradation of most CCR1 to CCR5 agonistic ligands. CCL14 is a homeostatic chemokine present at high concentrations in the serum with a weak agonist activity on CCR1. Under inflammatory conditions, plasmin and UPA-mediated truncation of 8 amino acids generates the potent CCR1/CCR3/CCR5 isoform CCL14(9-74), which is further processed and inactivated by dipeptidyl peptidase IV/CD26 that generates CCL14(11-74). Here we report that D6 efficiently binds both CCL14 and its truncated isoforms. Like other D6 ligands, the biologically active CCL14(9-74) induces adaptive up-regulation of D6 expression on the cell membrane and is rapidly and efficiently degraded. In contrast, the D6-mediated degradation of the biologically inactive isoforms CCL14(1-74) and CCL14(11-74) is very inefficient. Thus, D6 cooperates with CD26 in the negative regulation of CCL14 by the selective degradation of its biologically active isoform. Analysis of a panel of CC chemokines and their truncated isoforms revealed that D6-mediated chemokine degradation does not correlate with binding affinity. Conversely, degradation efficiency is positively correlated with D6 adaptive up-regulation. Sequence analysis indicated that a proline residue in position 2 of D6 ligands is dispensable for binding but crucial for D6 adaptive up-regulation and efficient degradation.

Adaptive distributed replica–exchange simulations

Owing to the loose coupling between replicas, the replica-exchange (RE) class of algorithms should be able to benefit greatly from using as many resources as available. However, the ability to effectively use multiple distributed resources to reduce the time to completion remains a challenge at many levels. Additionally, an implementation of a pleasingly distributed algorithm such as replica-exchange, which is independent of infrastructural details, does not exist. This paper proposes an extensible and scalable framework based on Simple API for Grid Applications that provides a general-purpose, opportunistic mechanism to effectively use multiple resources in an infrastructure-independent way. By analysing the requirements of the RE algorithm and the challenges of implementing it on real production systems, we propose a new abstraction (BigJob), which forms the basis of the adaptive redistribution and effective scheduling of replicas.

Female Scent Signals Enhances Male Resistance to Influenza

AbstractScent of receptive females as signal to reproduction stimulate male mice to olfactory search of a potential breeding partner^1, 2^. This searching behavior is coupled with infection risk due to bacterial contamination of the fecal and urine scent marks^4^. The theoretical consideration of host evolution under inevitable parasitic pressures, including helminthes, bacteria, virus etc., predicts adaptations that help protect against parasites associated with breeding^7^. In this study, we propose that acceptation of female signals by male mice leads to adaptive redistribution of immune defense directed to protection against respiratory infection risks. Our results reveal migration of macrophages and neutrophils to upper airways upon exposure to female odor stimulus resulting in increased resistance to influenza virus in male mice. Contrary to widely accepted immunosuppressive function of female sexual signals, our data provide the first demonstration of the adaptive immunological response to female odor stimulus through induction of nonspecific immune response in upper airways.

Involvement of the actin and tubulin networks in the trafficking of V‐ATPase, NBCe1‐A and NBCe1‐B in a submandibular duct cell line

Cytoskeletal components are established players in protein trafficking in epithelial cells. The bicarbonate‐secreting epithelium of salivary ducts is equipped with several acid‐base transporters whose cellular distribution is altered after systemic acid‐base disturbances. Here we investigated the role of actin and tubulin in V‐ATPase and electrogenic NBC1 distribution under physiological and pathological conditions in vitro. Therefore, extracellular acidosis or alkalosis was induced in the presence or absence of cytochalasin D or colchicine.Disruption of the actin network differentially influenced constitutive trafficking and adaptive redistribution after acid‐base disturbances. Following cytochalasin D treatment all transporters failed to reach the membrane. Trafficking of NBCe1‐B is impaired after disruption of the tubulin network as well, whereas localisation of NBCe1‐A was not affected by colchicine treatment during acid‐base disturbances.The results indicate differential regulation of tubulin‐mediated trafficking for NBCe1‐A and ‐B, reflecting their differences in the direction of ion transport and localisation in a polarized epithelium in vivo.This work was supported by the DFG.