Delivery Scheme Research Articles

Генезис логистических транспортных систем уровня 5-pl в свете новых антироссийских санкций

Purpose: To conduct an analytical study of the genesis of 5-pl logistic providing format in Russia taking into account the new conditions of external sanctions. In particular, the attempt was made to give answers to the questions: “What extent to, the changes in global transport and logistics market will affect business transformation in Russia? Whichsoever will the logistic transport systems become? What does doing business new format represent? How logistic transport systems transform into business ecosystems? What are the prerequisites for 5-pl genesis in Russia?” Methods: Analytical review method for Russia transport-logistic market state in the conditions of new sanctions is applied. Results: The analysis of new conditions that can be considered as prerequisites for the creation of fundamentally new formats of interaction in supply chains — the genesis of 5-pl providing — allows us to define 5-pl providing as an innovative mechanism for the improvement of the positions of logistic transport systems in the domestic market which’s undergone radical changes. Practical importance: An analytical review of the prerequisites and factors-accelerators for the formation of 5-pl logistic providing and of digital ecosystems in the context of new sanctions opposite Russia has been carried out. It’s been established that the genesis of 5-pl services of MaaS format contributes to the development of a new market on “online-assembling” of logistic delivery schemes based on the principles of logistics, transparency, import substitution, multimodality, digitalization, multivariance, customer orientation, quality and complexity. Based on the results of the study, the potential appearance of logistic transport systems of 5-pl digital ecosystem format as of March 2022 has been formulated.

A Secure Dynamic Content Delivery Scheme in Named Data Networking

Named data networking (NDN) is a promising alternative data dissemination technology of TCP/IP communication networks, which can bring out much more cost-effective and resilient communication in a highly mobile environment. However, due to the feature of NDN, content poisoning comes out as a potential threat. Hence, state-of-the-art studies introduce network layer approaches based on name-key binding, in which the producer notifies routers of the bindings of names and key values. Key values include publisher public key digest or content digest. Routers check key values to determine whether incoming data packets have been poisoned. Unfortunately, the approaches lead to more vulnerabilities in dynamic content poisoning because attackers can impersonate the producer to alter or fabricate the bindings. Thus, we introduce a consumer-oriented two-phased lightweight security scheme, which consists of an end-to-end authentication and a packet-level name-key query mechanism. Specifically, the name-key bindings are authenticated via an additional verification by the consumer. Furthermore, we also introduce a novel trust model to help routers to determine and disconnect from the malicious nodes. Finally, our extensive experimental results demonstrate that the scheme can work effectively in improving the vulnerability of existing studies on dynamic content poisoning and lowering the system overhead simultaneously.

Shaping the Optimal Technology for Servicing the Long-Distance Deliveries of Packaged Cargo by Road Transport

The concept of sustainable transportation of goods as the primary paradigm for designing contemporary logistics systems assumes the use of energy-efficient and affordable modes of transport in a way that guarantees the most cost-efficient variant of the delivery scheme. That especially applies to road transport deliveries, where the number of alternatives for organizing the transportation process is numerous and the choice of the optimal solution is complicated by the multiple stochastic influences of the environment on the technological processes. In this paper, we contribute to solving the problem of shaping the sustainable delivery schemes by proposing an approach to shape the complete set of alternative transport and technological schemes for packaged cargo delivery by road transport. The developed mathematical model allows estimating the efficiency of each alternative delivery scheme for the given request and chooses the best variant that minimizes the total costs of all participants in the delivery process. The proposed algorithms are implemented in the C# programming language within the frame of a class library for modeling transport delivery processes. A case of transport processes for Delivery Ltd. (Kharkiv, Ukraine) is applied to illustrate the procedure of using the developed approach to choose the optimal transport and technological schemes for long-distance deliveries. As the result of simulating the goods transportation processes, we show the regression models that represent dependencies of the total costs for the implementation of a delivery scheme from the parameters of demand for the transportation of goods. These regression models allow estimating the most efficient delivery schemes based on the functional analysis of the obtained dependencies for the given demand parameters.

Joint Disposition Properties and Comprehensive Pharmacokinetic Characterization of Antibody–Drug Conjugates

Antibody–drug conjugates (ADCs) comprise 3 distinct parts: a specific antibody carrier (mAb), a linker, and a cytotoxic payload. Typical pharmacokinetic (PK) characterization of ADCs remains fragmented using separate noncompartmental analyses (NCA) of individual analytes, offering little insight into the dynamic relationships among the ADC components, and the safety and efficacy implications. As a result, it is exceedingly difficult to compare ADCs in terms of favorable PK characteristics. Therefore, there is a need for characterizing ADCs using the joint disposition properties critical for understanding the fate of an ADC complex and clinical implications. In this communication, we describe 3 joint disposition metrics (JDMs) for integrated NCA of ADCs based on a combination of common analytes of ADC, payload, conjugated payload, and total mAb. These JDMs were derived, each in a simple form of a ratio between appropriate PK parameters of two analytes, from the presumed drug delivery scheme behind typical ADC designs, in terms of (1) linker stability, (2) therapeutic exposure ratio, and (3) effective drug-to-antibody ratio in vivo. The validity of the JDM-based PK characterization was examined against model-based analyses via their applications to 3 clinical candidates: PF-06650808, PF-06647020, and PF-06664178. For instance, the linker stability estimates for PF-06650808, PF-06647020, and PF-06664178 were 0.31, 0.14, and 0.096, respectively, from the JDM-based analyses vs. 0.23, 0.11, and 0.086 by the model-based approach. Additionally, the JDMs were estimated for a number of FDA-approved or otherwise well-documented ADCs, showing their utilities in comparing ADCs in terms of favorable PK characteristics.Graphical

Enhanced request adaptive scheme for information-centric vehicular networks

In this paper, we propose an enhanced request adaptive (EReA) scheme for content service provision in dynamic information-centric vehicular networking (ICVN) environment. The EReA scheme manages the cache update at the roadside units (RSUs) and provides low-latency content delivery to the end-users. User requests trigger the cache update at the RSU for a particular content item on the basis of its update−probability. We introduce an additional parameter tolerancei for each content item i. This parameter suppresses the frequency of content updates triggers at the RSU cache during high network load for the non-critical contents. This provides an additional saving in bandwidth. The simulation setup is created by ndnSIM 2.0 to validate the performance of this proposed scheme. The working and performance of the other content delivery schemes are also discussed in details. Results show that the proposed scheme provides a better hit-ratio compared to the existing ReA scheme under high network load, which results in an additional saving in bandwidth. Additionally, it also inherits the advantages of the ReA scheme.

Are cesarean deliveries equitable in India: assessment using benefit incidence analysis

BackgroundIn the last two decades, cesarean section (CS) deliveries in India have increased by six-fold and created economic hardship for families and households. Although several schemes and policies under the National Health Mission (NHM) have reduced the inequality in the use of maternal care services in India, the distributive effect of public health subsidies on CS deliveries remains unclear. In this context, this paper examines the usage patterns of CS delivery and estimates the share of public health subsidies on CS deliveries among mothers by different background characteristics in India.DataData from the fourth round of the National Family Health Survey (NFHS-4) was used for the study. Out-of-pocket (OOP) payment for CS delivery was used as a dependent variable and was analyzed by level of care that is, primary (PHC, UHC, other) and secondary (government/municipal, rural hospital). Descriptive statistics, binary logistic regression, benefit incidence analysis, concentration curve and concentration index were used for the analysis.ResultsA strong economic gradient was observed in the utilization of CS delivery from public health facilities. Among mothers using any public health facility, 23% from the richest quintile did not pay for CS delivery compared to 13% from the poorest quintile. The use of the public subsidy among mothers using any type of public health facility for CS delivery was pro-rich in nature; 9% in the poorest quintile, 16.1% in the poorer, 24.5% in the middle, 27.5% among richer and 23% in the richest quintile. The pattern of utilization and distribution of public subsidy was similar across the primary and secondary health facilities but the magnitude varied. The findings from the benefit-incidence analysis are supported by those obtained from the inequality analysis. The concentration index of CS was 0.124 for public health centers and 0.291 for private health centers. The extent of inequality in the use of CS delivery in public health centers was highest in the state of Mizoram (0.436), followed by Assam (0.336), and the lowest in Tamil Nadu (0.060), followed by Kerala (0.066).ConclusionThe utilization of CS services from public health centers in India is pro-rich. Periodically monitoring and evaluating of the cash incentive schemes for CS delivery and generating awareness among the poor would increase the use of CS delivery services in public health centers and reduce the inequality in CS delivery in India.

Contribution of general aviation to ensuring transport accessibility to the Arctic regions: the challenges and areas of focus

The article defines the dominant position of general aviation to ensure passenger transportation, to render the sanitary aviation and the Ministry of Emergencies services, taking into consideration the natural and climatic conditions of the Russian Federation Eastern Arctic. It analyzes the current state of the transport system of this territory, which is characterized by the railway communication lack, available roads for only seasonal purpose – winter roads, and the key role of water transport in the organization of freight transport based on the complex long-term (more than one year) multimodal delivery schemes, extremely high cost of regional and local air transportation. The purpose of the study is to analyze the state of the general aviation system in the Eastern Arctic of Russia and identify the factors, constraining its development, and to formulate proposals for their elimination. The article examines the state of the operating airport network, route network and operators’ fleet of aircraft – in service which render services to these territories. The limited airport network does not provide aviation accessibility to each settlement of the Arctic zone and causes transport discrimination. The lack of scheduled flights in local communication leads to increased waiting time for transportation and reduces demand. The outdated general aviation fleet with low economic efficiency is outcompeted by the helicopter service. The cost of a helicopter flight hour in the Arctic is 500–650 thousand rubles. The article considers the legal restrictions, that are associated with overstated requirements for companies and aviation enterprises serving the general aviation activities and hinder the development of local air transportation in the Arctic zone. Based on the analysis of foreign experience, the areas of focus to improve the Russian legislation, regulating the general aviation activities, which will allow us to reduce the costs to maintain the airport network, thereby stimulating its expansion for the purpose of increasing the level of transport accessibility to remote settlements of the Arctic zone, are proposed. The proposed measures to improve the air transport system in the Arctic zone are aimed to achieve the formulated targets.

VaCoChain: Blockchain-Based 5G-Assisted UAV Vaccine Distribution Scheme for Future Pandemics.

This paper proposes a generic scheme VaCoChain, that fuses blockchain (BC) and unmanned aerial vehicles (UAVs) underlying fifth-generation (5G) communication services for timely vaccine distribution during novel coronavirus (COVID-19) and future pandemics. The scheme offers 5G-tactile internet (5G-TI) based services for UAV communication networks (UAVCN) monitored through ground controller stations (GCs). 5G-TI enabled UAVCN supports real-time dense connectivity at ultra-low round-trip time (RTT) latency of [Formula: see text] and high availability of 99.99999%. Thus, it can support resilient vaccine distributions in a phased manner at government-designated nodal centers (NCs) with reduced round trip delays from vaccine production warehouses (VPW). Further, UAVCNs ensure minimizes human intervention and controls vaccine health conditions due to shorter trip times. Once vaccines are supplied at NCs warehouses, then the BC ensures timestamped documentation of vaccinated persons with chronology, auditability, and transparency of supply-chain checkpoints from VPW to NCs. Through smart contracts (SCs), priority groups can be formed for vaccination based on age, healthcare workers, and general commodities. In the simulation, for UAV efficacy, we have compared the scheme against fourth-generation (4G)-assisted long term evolution-advanced (LTE-A), orthogonal frequency division multiplexing (OFDM) channels, and traditional logistics for round-trip time (RTT) latency, logistics, and communication costs. In the BC setup, we have compared the scheme against the existing 5G-TI delivery scheme (Gupta et al.) for processing latency, packet losses, and transaction time. For example, in communication costs, the proposed scheme achieves an average improvement of 9.13 for block meta-information. For 4000 transactions, the proposed scheme has a communication latency of 16 s compared to 36 s. The packet loss is significantly reduced to 2.5% using 5G-TI compared to 16% in 4G-LTE-A. The proposed scheme has a computation cost of 1.6 ms and a communication cost of 157 bytes, which indicates the scheme efficacy against conventional approaches.

The impact of retirement on inpatient healthcare utilization in Guangzhou,\xa0China: a regression discontinuity analysis of 189,031 health insurance claims

BackgroundPrevious studies suggest that retirement, a major life event, affects overall healthcare utilization. We examine, the effects of retirement on inpatient healthcare utilization, including effect heterogeneity by gender, disease category, and type of health service.MethodsWe used routine health insurance claims data (N = 87,087) spanning the period 2021 - September 2013 from the Urban Employee Basic Medical Insurance (UEBMI), a mandatory social health insurance for working and retired employees in urban China. We applied a non-parametric fuzzy regression discontinuity design using the statutory retirement age in urban China as an exogenous instrument to measure the causal effect of retirement on six measures of inpatient healthcare utilization.ResultsRetirement reduced total hospital costs (-84.71 Chinese Yuan (CNY), 95% confidence interval (CI) -172.03 – 2.61), shortened length of hospital stays (-44.59, 95% CI -70.50 – -18.68), and increased hospital readmissions (0.06, 95% CI 0.00 – 0.12) and primary hospital visits (0.06, 95% CI 0.02 – 0.09) among women. Retirement did not significantly change inpatient healthcare utilization among men. The retirement effects among women varied by disease category. Specifically, retirement substantially increased hospitalizations for non-communicable diseases (NCDs), yet had only modest or no effect on hospitalizations for communicable diseases or injuries. Retirement effects among women also varied by the type of services. For relatively inexpensive services, such as nonoperative treatment, there were surges in the extensive margin (hospital readmission). For relatively expensive and invasive services, such as surgeries, retirement reduced the intensive margin (out-of-pocket expenditures and length of stay).ConclusionsRetirement decreases overall use of inpatient healthcare for women. The examination on the disease-related heterogeneous effects helps with the introduction and implementation of integrated healthcare delivery and appropriate incentive schemes to encourage better use of healthcare resources among older adults.

In vitro modified microdosimetric kinetic model–based predictions for B14-150 cells survival in 450 MeV/u carbon ion beam with aluminum ridge filter for biologically optimized spread-out Bragg peak

The relative biological efficiency of particle irradiation could be predicted with a wide variety of radiobiological models for various end-points. We validate the forecast of modified Microdosimetric Kinetic Model in vitro using combined data of reference Co-60 radiation and carbon ion plateau data for specific cell line to optimize the survival function in spread-out Bragg Peak obtained with an especially designed ridge filter. We used Geant4 Monte-Carlo software to simulate the fragment contribution along Bragg curve inside water phantom, open-source toolkit Survival to predict the expected linear-quadratic model parameters for each fragment, and in-house software to form the total survival curve in spread-out Bragg Peak. The irradiation was performed at U-70 synchrotron with an especially designed Aluminum ridge filter under the control of PTW and in-house ionization chambers. The cell clonogenic assay was conducted with the B14–150 cell line. The data analysis was accomplished using scipy and CERN ROOT. The clonogenic assay represents the survival in spread-out Bragg Peak at different points and qualitatively follows the modeled survival curve very well. The quantitative difference is within 3σ, and the deviation might be explained by the uncertainties of physical modeling using Monte-Carlo methods. Overall, the obtained results are promising for further usage in radiobiological studies or carbon ion radiotherapy. Shaping the survival curve in the region of interest (i.e., spread-out Bragg Peak) is a comprehensive task that requires high-performance computing approaches. Nevertheless, the method’s potential application is related to the development of next-generation treatment planning systems for ion beams. This can open a wide range of improvements in patient treatment outcome, provide new optimized fractionation regimes or optimized dose delivery schemes, and serve as an entrance point to the translational science approach.

WSN Location Privacy Scheme Enhancement through Epidemical Information Dissemination

Wireless Sensor Networks (WSNs) are commonly used for animal tracking. Over the years, a significant number of studies have been presented for monitoring moving targets through WSN. At the same time, the location / position information of each target should be available only to authorized entities, e.g., Animal Protection Centers, thus, the position should be kept private. The iHIDE is a location privacy mechanism that uses a non-geographical based routing scheme for packet delivery over WSN. In this paper, we elaborate on that scheme by introducing a routing plan construction algorithm. Furthermore, we enhance iHIDE by adopting the use of epidemical data dissemination as an enforcing privacy technique. Finally, we evaluate through simulations the scheme against other commonly used location privacy overlays in terms of network overhead and safety period.

Research on Mathematical Model of Balancing the Interests of All Parties in Food Delivery

In this paper, we study the delivery order pattern of take-out riders in Chinese society, adopt a time window function to give a reward and punishment measure for the complete quality of riders under various factors, and adopt hierarchical analysis to obtain and quantify the degree of influence of different factors on delivery, and get the commission scheme design so that the riders can get the maximum commission. Then, from the perspective of game theory, we establish a two-stage game model under the non-cooperative game, with the first stage of the game being the takeaway demand realizer and the second stage of the game being the takeaway demander and the contacting platform, and finally select a win-win solution with a balanced game. Finally, the pricing model proposed in the previous paper is optimized iteratively, considering the addition of long-distance as well as cross-regional distance quantification factors, and considering the case of dedicated personnel working exclusively. This paper proposes an equilibrium state for the four ends of the platform, merchants, consumers, and riders, and proposes a cross-regional and long-distance delivery scheme with certain feasibility, giving the platform and riders the possibility to expand the sales area and delivery area.

261 Engineering Synthetic Scaffolds to Achieve Periodontal Ligament Cell-Mediated Tissue Regeneration

OBJECTIVES/GOALS: Autologous periodontal ligament cells (PDLCs) are a promising tool for rebuilding tooth-supporting (periodontal) tissues but require scaffolds that enable delivery while maintaining PDLC bioactivity. The goal of this study was to design a synthetic hydrogel that fulfilled these criteria to support clinical translation of PDLC delivery. METHODS/STUDY POPULATION: Hydrogels were formed using poly(ethylene glycol) (PEG) polymers and synthetic peptides. PDLCs were isolated from human 3rd molars following informed consent and were cultured using established techniques. Integrin-binding peptides were utilized to promote specific PDLC behaviors, testing PDLCs from 3 human donors in a design of experiments (DOE) approach. Two promising hydrogel designs, identified in the DOE, were selected for validation testing using PDLCs from 3 additional donors. Finally, a small animal model for hydrogel-mediated PDLC delivery was used to determine if benchtop outcomes could predict in vivo tissue regeneration. RESULTS/ANTICIPATED RESULTS: Hydrogel scaffolds maintained high PDLC viability and controlled differentiation of each donor’s PDLCs based on differential presentation of integrin-binding peptides RGD and GFOGER. Two hydrogel designs were selected that optimized either PDLC alkaline phosphatase (ALP) activity or matrix mineralization, outcomes typically associated with cementum and bone formation. ALP activity-optimized hydrogels displayed enhanced PDLC pyrophosphate regulation while mineralization-optimized hydrogels promoted PDLC osteogenic differentiation. When used to deliver PDLCs to periodontal defects, both ALP activity-optimized and mineralization-optimized hydrogels stimulated new cementum formation with inserting PDL fibers, while mineralization-optimized hydrogels promoted enhanced bone formation. DISCUSSION/SIGNIFICANCE: Numerous challenges remain for translating PDLC regenerative potential to clinical practice. This study demonstrates that a synthetic hydrogel scaffold could overcome certain barriers, including controlling PDLC bioactivity with a simplified fabrication and delivery scheme, and may be a promising scaffold for periodontal tissue regeneration.

NOMA and Coded Multicasting in Cache-Aided Wireless Networks

Coded multicasting is considered to be an effective approach to simultaneously serve multiple users in the same frequency/time/code resource, which is made possible by exploiting the information available in users’ caches. Recently, non-orthogonal multiple access (NOMA) has emerged as an alternative transmission technique for cache-aided network. In cache-aided NOMA system, cache-enabled interference cancellation (CIC) is employed to cancel the interference using the information in the cache, and thus enhance the user transmission rate, particularly for the weak users. Despite the enhanced spectral efficiency offered by both techniques, complexity issue arises from handling large number of users. Therefore, user pairing/clustering should be employed to limit the number of users served in the same time-frequency resource. However, the key question is which delivery technique performs better under different pairing scenarios. In this paper, the performance of NOMA and coded multicasting for two-user pairing are investigated in terms of probability of sum rate comparison and outage probability. In order to exploit the benefits of NOMA and coded multicasting, we also propose a hybrid delivery scheme, which select either NOMA or coded multicasting depending on the channel conditions of the paired users in each resource block (RB). A joint mode selection, power allocation and user pairing scheme is developed to enhance the performance of the hybrid scheme. Both analytical and simulation results demonstrate that NOMA outperforms coded multicasting when pairing users whose channel gains are highly distinctive, while coded multicasting is preferred when the paired users have similar channel gains. In addition, the hybrid scheme is demonstrated to offer enhanced sum rate performance in comparison to NOMA and coded multicasting.

Metal–organic frameworks encapsulated with an anticancer compound as drug delivery system: Synthesis, characterization, antioxidant, anticancer, antibacterial, and molecular docking investigation

AbstractMetal organic framework (MOF) hybrid materials could be one of the answers in this investigation. We describe a simple and effective encapsulation of doxorubicin (DOX), an anticancer drug, inside Zr‐MOF, which have been little studied as drug delivery organizations. We investigated the measured release of the drug from Zr‐MOF in response to external incentives such as pH changes and interaction with biomimetic schemes. Zr‐MOF with encapsulated doxorubicin (DOX@Zr‐MOF) can be manufactured in one pot by addition the anticancer medication DOX to the reaction combination. They demonstrated pH‐responsive medication release and cancer cell killing capability. MOFs can be designed as multifunctional distribution vehicles for a diversity of loads, including medicinal and imaging agents, using our simple one‐pot approach. Fourier transform infrared (FTIR), X‐ray diffraction, scanning electron microscopy, and N2 sorption isotherm were used to analyze MOF and the developed drug delivery (DOX@Zr‐MOF) scheme. It investigated the effects of MOF and a bespoke drug delivery system on the feasibility of patient breast as well as liver tumor cell lines. At pH 5, the trapped drug can be released more quickly than at pH 7.4. Zr‐MOF nanoparticles had modest cytotoxicity; however, DOX@Zr‐MOF has higher cytotoxicity in MCF‐7 and HepG‐2 cells than DOX at concentrations greater than 31.25 μg ml−1. These results were discovered that DOX@Zr‐MOF could be a promising technique for delivering medicines to cancer cells. Furthermore, using the agar well dispersion technique, Zr‐MOF, DOX, and captured DOX@Zr‐MOF samples were assessed for their potential antibacterial activity against pathogenic bacteria in comparison to traditional antibiotics. In compared to the reference medication Gentamycin, the DOX@Zr‐MOF exhibits a large inhibitory zone against Gram negative organisms (Escherichia coli). The docking active place interactions were assessed to see if DOX might bind to the breast cancer 3hb5‐oxidoreductase receptor, prostate cancer protein 2q7k, and SARS‐CoV‐2 protease 6YB7 for anticancer and anticovid‐19 activities.

How may a generator manage the risk of PJM’s incentive scheme for capacity delivery?

Motivated by PJM’s recently proposed incentive scheme for capacity delivery during system emergencies, this paper develops two wholesale market products that a generator may use to manage the scheme’s risk. The first product is an insurance that removes the scheme’s downside risk due to the penalty for under-delivery. The second product is a forward contract that insulates a generator from the scheme’s risk due to the penalty for under-delivery and reward for over-delivery. The paper’s main contribution is how to price these newly developed products using readily available data.

Content Delivery Scheme Based on Network Selection for Power Saving

In this study, we present content delivery scheme based on network selection for power saving. There are two main communication technologies such as Wi-Fi and mobile telecommunication (4G, 5G) in smartphones. Power consumption is one of the important factors in smartphones. Wi-Fi network consumes low power compared to mobile telecommunication in multimedia streaming. The proposed scheme transmits the multimedia content data first when the Wi-Fi signal is strong. In this manner, it can reduce the energy consumption of a smartphone. Therefore, the proposed content delivery scheme is expected to be useful for providing multimedia streaming services with low-power consumption.

Vehicle-Assisted UAV Delivery Scheme Considering Energy Consumption for Instant Delivery.

Unmanned aerial vehicles (UAVs) are increasingly used in instant delivery scenarios. The combined delivery of vehicles and UAVs has many advantages compared to their respective separate delivery, which can greatly improve delivery efficiency. Although a few studies in the literature have explored the issue of vehicle-assisted UAV delivery, we did not find any studies on the scenario of an UAV serving several customers. This study aims to design a new vehicle-assisted UAV delivery solution that allows UAVs to serve multiple customers in a single take-off and takes energy consumption into account. A multi-UAV task allocation model and a vehicle path planning model were established to determine the task allocation of the UAVs as well as the path of UAVs and the vehicle, respectively. The model also considered the impact of changing the payload of the UAV on energy consumption, bringing the results closer to reality. Finally, a hybrid heuristic algorithm based on an improved K-means algorithm and ant colony optimization (ACO) was proposed to solve the problem, and the effectiveness of the scheme was proven by multi-scale experimental instances and comparative experiments.

Apoptotic body-inspired nanoparticles target macrophages at sites of inflammation to support an anti-inflammatory phenotype shift

Chronic inflammation is a significant pathological process found in a range of disease states. Treatments to reduce inflammation in this family of diseases may improve symptoms and disease progression, but are largely limited by variable response rates, cost, and off-target effects. Macrophages are implicated in many inflammatory diseases for their critical role in the maintenance and resolution of inflammation. Macrophages exhibit significant plasticity to direct the inflammatory response by taking on an array of pro- and anti-inflammatory phenotypes based on extracellular cues. In this work, a nanoparticle has been developed to target sites of inflammation and reduce the inflammatory macrophage phenotype by mimicking the anti-inflammatory effect of apoptotic cell engulfment. The nanoparticle, comprised of a poly(lactide-co-glycolide) core, is coated with phosphatidylserine (PS)-supplemented cell plasma membrane to emulate key characteristics of the apoptotic cell surface. The particle surface is additionally functionalized with an acid-sensitive sheddable polyethylene glycol (PEG) moiety to increase the delivery of the nanoparticles to low pH environments such as those of chronic inflammation. In a mouse model of lipopolysaccharide-induced inflammation, particles were preferentially taken up by macrophages at the site and promoted an anti-inflammatory phenotype shift. This PEGylated membrane coating increased the delivery of nanoparticles to sites of inflammation and may be used as a tool alone or as a delivery scheme for additional cargo to reduce macrophage-associated inflammatory response.

Parallel model exploration for tumor treatment simulations

AbstractComputational systems and methods are often being used in biological research, including the understanding of cancer and the development of treatments. Simulations of tumor growth and its response to different drugs are of particular importance, but also challenging complexity. The main challenges are first to calibrate the simulators so as to reproduce real‐world cases, and second, to search for specific values of the parameter space concerning effective drug treatments. In this work, we combine a multi‐scale simulator for tumor cell growth and a genetic algorithm (GA) as a heuristic search method for finding good parameter configurations in reasonable time. The two modules are integrated into a single workflow that can be executed in parallel on high performance computing infrastructures. In effect, the GA is used to calibrate the simulator, and then to explore different drug delivery schemes. Among these schemes, we aim to find those that minimize tumor cell size and the probability of emergence of drug resistant cells in the future. Experimental results illustrate the effectiveness and computational efficiency of the approach.