Cargo Transfer Research Articles

Laser-Induced Intracellular Delivery: Exploiting Gold-Coated Spiky Polymeric Nanoparticles and Gold Nanorods under Near-Infrared Pulses for Single-Cell Nano-Photon-Poration.

This study explores the potential of laser-induced nano-photon-poration as a non-invasive technique for the intracellular delivery of micro/macromolecules at the single-cell level. This research proposes the utilization of gold-coated spiky polymeric nanoparticles (Au-PNPs) and gold nanorods (GNRs) to achieve efficient intracellular micro/macromolecule delivery at the single-cell level. By shifting the operating wavelength towards the near-infrared (NIR) range, the intracellular delivery efficiency and viability of Au-PNP-mediated photon-poration are compared to those using GNR-mediated intracellular delivery. Employing Au-PNPs as mediators in conjunction with nanosecond-pulsed lasers, a highly efficient intracellular delivery, while preserving high cell viability, is demonstrated. Laser pulses directed at Au-PNPs generate over a hundred hot spots per particle through plasmon resonance, facilitating the formation of photothermal vapor nanobubbles (PVNBs). These PVNBs create transient pores, enabling the gentle transfer of cargo from the extracellular to the intracellular milieu, without inducing deleterious effects in the cells. The optimization of wavelengths in the NIR region, coupled with low laser fluence (27 mJ/cm2) and nanoparticle concentrations (34 µg/mL), achieves outstanding delivery efficiencies (96%) and maintains high cell viability (up to 99%) across the various cell types, including cancer and neuronal cells. Importantly, sustained high cell viability (90-95%) is observed even 48 h post laser exposure. This innovative development holds considerable promise for diverse applications, encompassing drug delivery, gene therapy, and regenerative medicine. This study underscores the efficiency and versatility of the proposed technique, positioning it as a valuable tool for advancing intracellular delivery strategies in biomedical applications.

Experimental Study on Adaptive Backstepping Synchronous following Control and Thrust Allocation for a Dynamic Positioning Vessel

Cargo transfer vessels (CTVs) are designed to transfer cargo from a floating production storage and offloading (FPSO) unit into conventional tankers. The dynamic positioning system allows the CTV to maintain a safe position relative to the FPSO unit using a flexible cargo transmission pipe, and the CTV tows the tanker during operating conditions. The operation mode can be considered a synchronization tracking control problem. In this paper, a synchronization control strategy is presented based on the virtual leader–follower configuration and an adaptive backstepping control method. The position and heading of the following vessel are proven to be able to globally exponentially converge to the virtual ship by the contraction theorem. Then, the optimization problem of the desired thrust command from the controller is solved through an improved firefly algorithm, which fully considers the physical characteristics of the azimuth thruster and the thrust forbidden zone caused by hydrodynamic interference. To validate the effectiveness of the presented synchronous following strategy and thrust allocation algorithm, a scale model experiment is carried out under a sea state of 4 in a seakeeping basin. The experimental results show that the CTV can effectively maintain a safe distance of 100 m with a maximum deviation of 3.78 m and an average deviation of only 0.99 m in the wave heading 180°, which effectively verifies that the control strategy proposed in this paper can achieve safe and cooperative operation between the CTV and the FPSO unit. To verify the advantages of the SAF algorithm in the thrust allocation, the SQP algorithm and PSO algorithm are used to compare the experimental results. The SAF algorithm outperforms the SQP and PSO algorithms in longitudinal and lateral forces, with the R-squared (R2) values of 0.9996 (yaw moment), 0.9878 (sway force), and 0.9596 (surge force) for the actual thrusts and control commands in the wave heading 180°. The experimental results can provide technical support to improve the safe operation of CTVs.

Facilitating Interskin Communication in Artificial Polymer Systems through Liquid Transfer.

Chemical communication is a ubiquitous process in nature, and it has sparked interest in the development of electric-sense-based robotic perception systems with chemical components. Here, a novel liquid crystal polymer is introduced that combines the transferring, receiving, and sensing of chemical signals, providing a new principle to achieve chemical communication in robotic systems. This approach allows for the transfer of cargo between two polymer coatings, and the transfer can be monitored through an electrical signal. Additionally, cascade transfer can be achieved through this approach, as the transfer of cargo is not limited to only two coatings, but can continue from the second to a third coating. Furthermore, the two coatings can be infused with different reagents, and upon exchange, a reaction takes place to generate the desired species. The novel method of chemical communication that is developed presents a notable improvement in embodied perception. This advancement facilitates human-robot and robot-robot interactions and enhances the ability of robots to efficiently and accurately perform complex tasks in their environment.

Immunometabolism, extracellular vesicles and cardiac injury.

Recent evidence from our lab and others suggests that metabolic reprogramming of immune cells drives changes in immune cell phenotypes along the inflammatory-to-reparative spectrum and plays a critical role in mediating the inflammatory responses to cardiac injury (e.g. hypertension, myocardial infarction). However, the factors that drive metabolic reprogramming in immune cells are not fully understood. Extracellular vesicles (EVs) are recognized for their ability to transfer cargo such as microRNAs from remote sites to influence cardiac remodeling. Furthermore, conditions such as obesity and metabolic syndrome, which are implicated in the majority of cardiovascular disease (CVD) cases, can skew production of EVs toward pro-inflammatory phenotypes. In this mini-review, we discuss the mechanisms by which EVs may influence immune cell metabolism during cardiac injury and factors associated with obesity and the metabolic syndrome that can disrupt normal EV function. We also discuss potential sources of cardio-protective and anti-inflammatory EVs, such as brown adipose tissue. Finally, we discuss implications for future therapeutics.

Planning rolling stock operation in international communications with modern requirements to cargo transportation technology

Introduction. The relevance of the research carried out is justified by the need to plan performance indicators of rolling stock in the context of changes in the technology of cargo transportation in international traffic when implementing the Draft Order of the Ministry of Transport of the Russian Federation. An obligatory element in the technology of cargo transportation is the re-coupling of a semi-trailer or reloading of cargo. In practice, there are additional costs for the transportation of goods due to the significant waiting time for interchange due to the deviation of the time of arrival of rolling stock transporting goods in international traffic to the interchange point in accordance with the contract from the planned time of arrival at the interchange point. Today, there is no methodology for planning the operation of rolling stock of road transport in international traffic that takes into account modern requirements for the technology of cargo transportation in terms of eliminating waiting time at the point of transfer or reloading of cargo. The purpose of this article is to develop an algorithm for a planning methodology based on the mathematical model of the functioning of rolling stock in international traffic, created for the first time by the authors, taking into account modern requirements for cargo transportation technology.Materials and methods. To achieve the purpose of the study, the scientific foundations of current planning of the work of a motor transport enterprise are applied. The development of a mathematical model for the functioning of rolling stock in international traffic was carried out on the basis of the criterion - minimum transportation costs, taking into account the duration of technological operations, including waiting time at the point of transfer or reloading of cargo. The systematic nature of the study lies in the fact that the properties of cargo transportation are manifested in relation to rolling stock and depend not only on the properties of the cargo, but also on transportation technology, the time of completion of the transport process, which are established in the contract and affect the performance of the rolling stock.Results. The use of planning methodology for the practice of functioning of rolling stock in international traffic, taking into account modern requirements for cargo transportation technology, was carried out using the example of transporting a disassembled hydraulic vulcanization press. Software and mathematics have been developed to calculate costs.Conclusions. A methodology for planning the functioning of rolling stock in international traffic has been developed, taking into account modern requirements for the technology of cargo transportation based on the created mathematical model, using regulatory requirements for the transportation of goods in international traffic and promising theoretical studies. Practical implementation is presented using the example of a DAF XF 480 FT truck tractor with a Kogel S24-1 semi-trailer.

Intercellular contact and cargo transfer between Müller glia and to microglia precede apoptotic cell clearance in the developing retina.

To clarify our understanding of glial phagocytosis in retinal development, we used real-time imaging of larval zebrafish to provide cell-type specific resolution of this process. We show that radial Müller glia frequently participate in microglial phagocytosis while also completing a subset of phagocytic events. Müller glia actively engage with dying cells through initial target cell contact and phagocytic cup formation, after which an exchange of the dying cell from Müller glia to microglia often takes place. In addition, we find evidence that Müller glia cellular material, possibly from the initial Müller cell phagocytic cup, is internalized into microglial compartments. Previously undescribed Müller cell behaviors were seen, including cargo splitting, wrestling for targets and lateral passing of cargo to neighbors. Collectively, our work provides new insight into glial functions and intercellular interactions, which will allow future work to understand these behaviors on a molecular level.

Neuroserpin and Extracellular Vesicles in Ischemic Stroke: Partners in Neuroprotection?

Ischemic stroke represents a significant global health challenge, often resulting in death or long-term disability, particularly among the elderly, where advancing age stands as the most unmodifiable risk factor. Arising from the blockage of a brain-feeding artery, the only therapies available to date aim at removing the blood clot to restore cerebral blood flow and rescue neuronal cells from death. The prevailing treatment approach involves thrombolysis by administration of recombinant tissue plasminogen activator (tPA), albeit with a critical time constraint. Timely intervention is imperative, given that delayed thrombolysis increases tPA leakage into the brain parenchyma, causing harmful effects. Strategies to preserve tPA's vascular benefits while shielding brain cells from its toxicity have been explored. Notably, administering neuroserpin (Ns), a brain-specific tPA inhibitor, represents one such approach. Following ischemic stroke, Ns levels rise and correlate with favorable post-stroke outcomes. Studies in rodent models of focal cerebral ischemia have demonstrated the beneficial effects of Ns administration. Ns treatment maintains blood-brain barrier (BBB) integrity, reducing stroke volume. Conversely, Ns-deficient animals exhibit larger stroke injury, increased BBB permeability and enhanced microglia activation. Furthermore, Ns administration extends the therapeutic window for tPA intervention, underscoring its potential in stroke management. Remarkably, our investigation reveals the presence of Ns within extracellular vesicles (EVs), small membrane-surrounded particles released by all cells and critical for intercellular communication. EVs influence disease outcome following stroke through cargo transfer between cells. Clarifying the role of EVs containing NS could open up urgently needed novel therapeutic approaches to improve post-ischemic stroke outcome.

A Framework for In-Car Loading Optimization Problem

Speed is a crucial evaluation criterion in the cargo transportation industry. The processes carried out during transfers before cargo reaches the destination unit are vital for timely delivery. Time spent at cargo distribution centers should be minimized, the maximum number of packages should be transported in a single action between transfers, and cargo vehicles should be used as accurately and efficiently as possible. Minimizing unused space inside the vehicles and ensuring that vehicles at cargo transfer centers are arranged correctly and efficiently for faster departures and increased cargo capacity are of great importance. In pursuit of this goal, the present research concentrates on optimizing the loading of vehicle interiors. This investigation proposes a method that determines the optimal dimensions of packages to be loaded within the vehicle, with the intention of maximizing the number of cargo packages while minimizing the interior volume used. A preliminary implementation of the suggested approach has been created. This developed prototype application can assist cargo transportation companies in planning their cargo loading and optimizing the utilization of vehicle interiors. The efficacy of the prototype application was evaluated using a representative vehicle loading dataset, and the results demonstrate its success.

A novel magnetorheological anti-swing system for offshore crane: System modeling and controller design

Constrained by the unique operational conditions and the swinging motion of the payload, offshore cranes exhibit low lifting efficiency and positioning accuracy during operation. In this paper, magnetorheological (MR) technology is applied in the realm of payload anti-swing and positioning of offshore cranes for the first time. The anti-swing system adopts a parallel mechanical configuration design, offering a simple structure that does not encroach upon the crane's working space and exhibits high levels of robustness. Based on the principle of robotics, the kinematic and dynamic model of anti-swing system is derived. Co-simulation analysis is conducted to assess the swing response of the crane's payload throughout the lifting and transfer process amidst irregular ocean waves. The findings demonstrate that the MR anti-swing system effectively mitigates payload swing, achieving an anti-swing effect of over 80%. With a similar anti-swing effect, the MR anti-swing system with time-varying current reduces energy consumption by 54% compared to the system with fixed current. Subsequently, experimental results from the physical prototype reveal that the anti-swing system can suppress payload swing by over 80% during cargo transfer processes. This underscores the capability of the MR anti-swing system to enhance payload transfer efficiency and positioning accuracy.

Imaging of Light-Enhanced Extracellular Vesicle-Mediated Delivery of Oxaliplatin to Colorectal Cancer Cells via Laser Ablation, Inductively Coupled Plasma Mass Spectrometry.

Extracellular vesicles (EVs) are lipid bilayer structures released by all cells that mediate cell-to-cell communication via the transfer of bioactive cargo. Because of the natural origin of EVs, their efficient uptake by recipient cells, capacity to stabilize and transport biomolecules and their potential for cell/tissue targeting and preferential uptake by cancer cells, they have enormous potential for bioengineering into improved and targeted drug delivery systems. In this work, we investigated the use of laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) as a tool to measure the loading of platinum-based chemotherapeutic agents. The EV loading of oxaliplatin via co-incubation was demonstrated, and LA-ICP-MS imaging showed greater efficiency of delivery to colorectal cancer cells compared to free oxaliplatin, leading to enhanced cytotoxic effect. Further, the impact of EV co-loading with a porphyrin (C5SHU, known as 'C5') photosensitizer on oxaliplatin delivery was assessed. Fluorescence analysis using nano-flow cytometry showed dose-dependent EV loading as well as a trend towards the loading of larger particles. Exposure of OXA-C5-EV-treated colorectal cancer cells to light indicated that delivery was enhanced by both light exposure and porphyrins, with a synergistic effect on cell viability observed between oxaliplatin, EVs and light exposure after the delivery of the co-loaded EVs. In summary, this work demonstrates the utility of LA-ICP-MS and mass spectrometry imaging in assessing the loading efficiency and cellular delivery of platinum-based therapeutics, which would also be suitable for agents containing other elements, confirms that EVs are more efficient at delivery compared to free drugs, and describes the use of light exposure in optimizing delivery and therapeutic effects of EV-mediated drug delivery both in combination and independently of porphyrin-based photosensitizers.

Exploring the Cargo Potential: A Comprehensive Analysis of Kertajati Airport

Kertajati Airport was constructed to cater the growing demand from West Java Province and its surrounding areas, aiming to address the limitations faced by the previous airport, Husein Sastranegara International Airport in Bandung. The intention was to relieve pressure from Soekarno-Hatta International Airport and accommodate passengers from the former airport. However, since its inauguration in 2018, the airport's activities have fallen short of initial expectations. In response to this challenge, the West Java Provincial Government has strategized to reposition Kertajati Airport as a dedicated cargo-centric facility, aiming to pivot its focus to a financial solution. This study encompasses an in-depth analysis of the cargo potential, considering the key commodities within West Java, strategies for cargo transfer from Soekarno-Hatta and Husein Sastranegara airports, estimated travel time and associated costs to Kertajati Airport, and the most efficient aircraft types for cargo transportation. The findings reveal that Kertajati Airport's catchment area encompasses 19 districts/cities (70%) within West Java and 3 districts/cities (9%) in Central Java. The demand forecasting analysis projects the volume for international and domestic cargo in 2028 originating from Soekarno-Hatta Airport, indicating a 13% transfer, are 62 tons and 56 tons, respectively. Concurrently, the anticipated demand volume for international and domestic cargo transfer from Husein Sastranegara Airport in 2023 are 4 tons and 30 tons, respectively. The concentration of cargo potential lies prominently in areas rich in key commodities, notably Bandung City, Bandung Barat District, Tasikmalaya District, Garut District, and Sumedang District. The results indicate that there is a potential to promote the Kertajati Airport into a cargo-centric facility. More deep research with more data will give more confidence to focus in developing this facility.

Extracellular Vesicles Secreted from Daratumumab Resistant Cells Promote Resistance and Proliferation of Daratumumab Sensitive Cells, Possibly through the Transfer of miRNA Cargo

Multiple Myeloma (MM) is the second most common hematologic malignancy and remains incurable. Daratumumab (dara) is a potent anti-CD38 monoclonal antibody used for MM treatment, but responses are heterogeneous, and resistance is inevitable. There is hence an urgent need for identification of biomarkers to predict responses and in-depth characterisation of mechanisms of resistance. We have previously demonstrated that the exosome biogenesis pathway plays a significant role in the survival of dara resistant (dara R) cell lines. Here, we highlight that the enriched expression of exosome pathway proteins reported in dara R cell lines is not detected in Lenalidomide or Bortezomib-resistant cell lines, or in other monoclonal antibody resistant cell lines such as anti-CD20 (Rituximab)-resistant cell lines, thus indicating that this mechanism is unique to daratumumab resistance. Coculture of dara sensitive (dara S) cell lines with dara R cell lines separated by a cell-impermeable transwell insert promoted cell proliferation and reduced response to dara treatment in dara S cell lines thereby suggesting a potential role for extracellular vesicles (EVs) secreted by dara R cells in mediating these responses. In this study, we seek to investigate the role of EVs secreted by dara R cells, in particular, that of EV-derived miRNAs in the tumour microenvironment which can help predict and mediate dara resistance. We have originally described the establishment of three dara R cell lines in Natural Killer T-cell Lymphoma (NKTL), T-cell acute lymphoblastic leukaemia (T-ALL) and MM via long-term exposure to increasing concentrations of dara. To assess the specific role of EVs in mediating resistance, we isolated and purified EVs from the media of dara R cell lines and added it to the culture of dara S cells. To confirm uptake of dara R EVs by sensitive cell lines, EVs isolated from resistant cell lines were stained with PKH26 and characterised by binding to CD81 and CD63 beads via flow cytometry. Uptake of dara R EVs by dara S cell lines was confirmed through flow cytometry and confocal microscopy. We observed that uptake of dara R EVs directly promote proliferation and reduced cytotoxic response to dara treatment in dara S cells. Next, we assessed the effect of inhibiting dara R EV secretion by applying Neticonazole and Ketoconazole, prior to coculture of resistant and sensitive cell lines. Interestingly, coculturing azole-treated resistant cell lines with sensitive cell lines mitigated the increase in proliferation and dara resistance. Exosomal miRNAs are known to play a pivotal role in regulating cellular pathways driving cancer cell resistance and survival. To evaluate the potential role of EV-derived miRNA cargo, we first extracted miRNAs from the EVs purified from dara R and dara S cell lines and then performed an miRNA profiling screen with the PanoramiR panel (MiRXES) which targets 376 miRNAs expertly curated from miRBase 22, HMDD 3.2 and The Cancer Genome Atlas. We discovered that EVs derived from resistant cell lines expressed higher levels of proliferative miRNAs, miR-155 and miR-181a. These findings were validated through qPCR, confirming the increased expression of these miRNAs in both resistant cell lines and EVs derived from resistant cell lines. We also observed a concomitant downregulation of mir-155 target genes such as BACH1, JARID2 and SMAD5 in the resistant cell lines. This positive observation led us to extend the study into the clinic. Extracellular vesicles were isolated from the plasma fraction of bone marrow samples obtained from 17 patients with MM prior to treatment with dara based combinations either in the upfront or relapsed setting. miRNA extraction was performed and samples evaluated by miRNA sequencing. We found that the EVs from patients with a progression free survival (PFS) of less than 2 years after dara based therapy (dara R patients) had an enrichment of mir-155 and mir-181a as compared to those with a PFS longer than 2 years. These data align with our findings in the cell lines and suggest that these miRNAs may be utilised as potential biomarkers for daratumumab resistance. We are currently elucidating the biological basis for dara resistance mediated by these miRNAs. A deeper understanding of the mechanisms involved may pave the way for clinical evaluation of EV- directed therapeutics to overcome dara resistance.

Extracellular vesicles-Mediators of opioid use disorder?

Opioid use disorder (OUD) is a growing health emergency in the United States leading to an epidemic of overdose deaths. OUD is recognized as an addictive brain disorder resulting in psychological, cognitive and behavioural dysfunction. These observed clinical dysfunctions are a result of cellular changes that occur in the brain. Derangements in inflammation, neurogenesis and synaptic plasticity are observed in the brains of OUD patients. The mechanisms of these derangements are unclear; however, extracellular vesicles (EVs), membrane bound particles containing protein, nucleotides and lipids are currently being investigated as agents that invoke these cellular changes. The primary function of EVs is to facilitate intercellular communication by transfer of cargo (protein, nucleotides and lipids) between cells; however, changes in this cargo have been observed in models of OUD suggesting that EVs may be agents promoting the observed cellular derangements. This review summarizes evidence that altered cargo of EVs, specifically protein and miRNA, in models of OUD promote impairments in neurons, astrocytes and microglial cells. These findings support the premise that opioids alter EVs to detrimentally affect neuro-cellular function resulting in the observed addictive, psychological and neurocognitive deficits in OUD patients.

Simulation and optimization of transfer system for ore terminal with complex waterways

Terminal towing and barging operations play a critical role in cargo transfer within ports, especially in complex waterways. Scheduling of barges and tugs is influenced by various factors, such as speed, and the operation planning must consider the constraints of channel traffic. Additionally, the transfer system involves constructing and operating berths, transshipment equipment, barges, tugboats, and other resources. Effective scheduling and resource planning are crucial for achieving sustainability. To illustrate this point, we analyze the estuary barging process in a real-world case. We utilize the Anylogic platform to simulate the entire process of ore terminal loading, river transportation, and sea transshipment. Furthermore, we employ simulation-based optimization methods to enhance the system’s performance. Our case study has yielded valuable management insights, including: (1) Key variables related to shipping speeds and resource allocation are identified and optimized; (2) A specific tug dispatch rule has been verified to outperform other options in terms of efficiency and emissions; (3) The potential benefits of constructing and enabling an additional terminal have been identified. Our exploration provides quantitative support for decision-making related to vessel scheduling and resource planning in engineering projects for ore terminals.

Interplay of Extracellular Vesicles and TLR4 Signaling in Hepatocellular Carcinoma Pathophysiology and Therapeutics.

Hepatocellular carcinoma (HCC) stands as a significant contributor to global cancer-related mortality. Chronic inflammation, often arising from diverse sources such as viral hepatitis, alcohol misuse, nonalcoholic fatty liver disease (NAFLD), and nonalcoholic steatohepatitis (NASH), profoundly influences HCC development. Within this context, the interplay of extracellular vesicles (EVs) gains prominence. EVs, encompassing exosomes and microvesicles, mediate cell-to-cell communication and cargo transfer, impacting various biological processes, including inflammation and cancer progression. Toll-like receptor 4 (TLR4), a key sentinel of the innate immune system, recognizes both pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs), thereby triggering diverse signaling cascades and pro-inflammatory cytokine release. The intricate involvement of the TLR4 signaling pathway in chronic liver disease and HCC pathogenesis is discussed in this study. Moreover, we delve into the therapeutic potential of modulating the TLR4 pathway using EVs as novel therapeutic agents for HCC. This review underscores the multifaceted role of EVs in the context of HCC and proposes innovative avenues for targeted interventions against this formidable disease.

Epstein-Barr virus LMP1 enhances levels of large extracellular vesicle-associated PD-L1.

A growing body of evidence has supported the notion that viruses utilize EVs and associated pathways to incorporate viral products. This allows for the evasion of an immune response while enabling viral spread within the host. Given that viral proteins often elicit strong antigenic peptides that are recognized by T cells, the regulation of the PD-L1 pathway through the overexpression of lEV-associated PD-L1 may serve as a strategy for immune evasion by viruses. The discovery that EBV LMP1 increases the secretion of PD-L1 in larger EVs identifies a new potential target for immune blockade therapy in EBV-associated cancers. Our findings may help to clarify the mechanism of LMP1-mediated enhancement of PD-L1 packaging into lEVs and may lead to the identification of more specific targets for treatment. Additionally, the identification of lEV biomarkers that predict a viral origin of disease could allow for more targeted therapies to be developed.

Two-echelon vehicle routing problem with direct deliveries and access time windows

Nowadays, heavy-duty trucks are usually restricted from entering urban areas due to emission and congestion problems in most cities. So, a two-echelon distribution system becomes vastly applicable, in which satellites transfer cargo and avoid heavy-duty trucks entering urban areas. However, with the development of new energy vehicles and access policies and regulations, some environmentally friendly trucks are accessible to urban areas within specific time windows of daytime directly. In light of this, we introduce a two-echelon vehicle routing problem with direct deliveries and access time windows (2E-VRPDDATW) arising in city logistics. In this problem, customers are served by the two-echelon distribution systems within their required time windows and are allowed to be directly delivered by the first echelon vehicles within access time windows, which provides more flexible routing schemes. A novel mixed integer linear programming (MILP) model for the above problem is presented, and the corresponding adaptive large neighborhood algorithm is developed. The computational experiments are provided to verify the validity of the proposed model and the effectiveness of the algorithm. Finally, the sensitivity analysis shows some interesting findings about the number of two-echelon vehicles and the assignment of customers. Moreover, we conclude that direct deliveries are advantageous in transportation costs when the proportion of the end time of access time window to the last end time of customers is greater than 0.25.

Analisis Manajemen Risiko pada Tingkat Kinerja Pelayanan Kapal di PT X

Loading and unloading activities are the transfer of cargo from ship to port or vice versa. One of the loading and unloading activities is on liquid bulk cargo. Loading and unloading activities are related to ship services, namely ET indicators: BT. One of the indicators is Idle Time (IT). Idle Time (IT) is the number of unused working hours during loading and unloading work time at the mooring. IT value < RKAP indicates minimal obstacles to loading and unloading operations. The purpose of this study is to analyze Idle Time in liquid bulk loading and unloading activities every month and analyze the factors that can affect the performance of liquid bulk loading and unloading in 2021 at Company X. This research uses descriptive quantitative methods. The results of the analysis of Company X, namely Idle Time (IT) are not good because IT> RKAP. There are obstacles in loading and unloading activities due to various factors. The inhibiting factors are tool factors, environmental factors and worker factors. This requires good risk management.

Mitochondrial transfer from cancer-associated fibroblasts increases migration in aggressive breast cancer.

Cancer-associated fibroblasts (CAFs) have distinct roles within the tumor microenvironment, which can impact the mode and efficacy of tumor cell migration. CAFs are known to increase invasion of less-aggressive breast cancer cells through matrix remodeling and leader-follower dynamics. Here, we demonstrate that CAFs communicate with breast cancer cells through the formation of contact-dependent tunneling nanotubes (TNTs), which allow for the exchange of cargo between cell types. CAF mitochondria are an integral cargo component and are sufficient to increase the 3D migration of cancer cells. This cargo transfer results in an increase in mitochondrial ATP production in cancer cells, whereas it has a negligible impact on glycolytic ATP production. Manually increasing mitochondrial oxidative phosphorylation (OXPHOS) by providing extra substrates for OXPHOS fails to enhance cancer cell migration unless glycolysis is maintained at a constant level. Together, these data indicate that tumor-stromal cell crosstalk via TNTs and the associated metabolic symbiosis is a finely controlled mechanism by which tumor cells co-opt their microenvironment to promote cancer progression and may become a potential therapeutic target.

DEM Based Wear Analysis and Optimization of the Chute System in Transfer Stations

With the increasing application of bulk cargo transfer station in ports, it is one of key problems to effectively solve the wear problem of the chute system and to reduce the maintenance cost of port equipment and improve the production efficiency. Taking the actual wear of the chute as an example, this paper analyzed the causes of the wear of the chute system used in the bulk cargo transfer station based on the discrete element method (DEM), and the problems of the original chute design was revealed. On this basis, the optimization scheme of chute was put forward from two aspects of reducing the wear degree and facilitating the replacement of lining plate.