Search

Probe vehicles and loop detectors collect traffic data for empirical MFD estimation. The accuracy of MFD estimation is contingent upon the percentage of road network links covered (road coverage) and the extent of information (penetration rate) from each link. While the previous research has explored the effects of loop detector road coverage and probe vehicle penetration rates, the impact of probe vehicle road coverage remains unaddressed. Furthermore, the unequal distribution and low penetration rates of probe vehicles undermine the reliability of the data obtained from them. Therefore, this study aimed to (i) examine the impact of probe vehicle road coverage on MFD estimation, (ii) enhance the reliability of the spatial data by using speed data reconstruction, (iii) highlight the increased role of spatial data in the accuracy of MFD estimation, and (iv) develop a performance factor of speed data quality to demonstrate that the quality of spatial data is more susceptible to the penetration rate than road coverage. The results underlined the role of FCD road coverage in MFD estimation, and the proposed methodology significantly improves spatial data quality. The study concluded that spatial and temporal data affect the MFD estimation differently, and the proposed performance factor increases the role of spatial data in MFD estimation.

As the airspace is increasingly gaining importance as a new frontier to improve urban mobility, aerial cable cars are being discussed and already appropriately implemented worldwide to supplement conventional modes of transport in urban areas. Transit planners and designers should carefully consider the interoperability and integration of cable car services with conventional modes of transport. In particular, excessive delays and overcrowding conditions due to deficits in interoperability should be avoided. This challenge of interoperability arises as conventional modes of transport operate predominantly on a timetable, and most cable car technologies operate in such close headways that they can be considered as almost continuous conveyors. The advantage of having almost always a transport vessel of a cable car ready for boarding ceases when large volumes of passengers arrive in batches, for example from higher-capacity modes of transport or at large events, resulting in long queues. Traditional manuals do not yet reflect these aspects of interoperability adequately. Consequently, this work filled this research gap about the interoperability of cable cars related to handling high volumes of incoming passenger arrivals that transfer in larger batches from feeder modes and often result in queues at cable car stations. The following objectives were targeted: (1) determine passenger capacity limits of conventional modes of transport acting as feeders to cable cars and (2) specify space requirements to be provided due to the potential queues that arise. To answer these, methods of Queuing Theory were used and results were placed in Levels of Services of traditional manuals. Key performance indicators included queue length, waiting time, and corresponding queue space. The results revealed that cable cars can be a useful complement to public transit but are of limited feasibility due to cumulative queues at arrival rates with larger crowds. High-capacity feeder modes (e.g., commuter rails) are limited to 20-minute headways depending on cable car technologies. Further, queuing areas of up to 1000 square meters (around 10,800 ft2) should be considered. Several operational limitations are presented as guidance for practitioners and policymakers.

Shared space design aims to establish an environment in which pedestrians, cyclists, and motor vehicles can interact and coexist harmoniously. To identify whether pedestrians and cyclists equally favour attributes that attract, engage, and protect them in the space, this paper explores their preferences for shared space design in configurations that emphasise the sense of place, integration, and informal segregation. In an online survey, 408 participants experienced videos of virtual environments with different designs to assess various attributes and their influence on the perception of the space and crossing behaviour. The results indicate that pedestrians and cyclists do favour similar attributes and space configurations. While both find motor vehicles undesirable, they hold a positive view of the central placement of design elements and protective barriers separating them from other road users. To design liveable environments that integrate and accommodate road users’ needs, this paper reiterates that it is crucial to systematically structure the space to deliver the concept of integration while reinforcing the place function and providing a sense of protection for vulnerable road users. Distinct design elements and their strategic placement, such as a centrally located fountain, can also further enhance the overall appeal of the design.

Sensitive methods for antibody detection tend to be expensive and slow. Here, the authors report a magnetic particle spectroscopy method named COMPASS, as a rapid and low-cost technique which is comparable to ELISA in terms of sensitivity but with a measurement times of seconds.

Background and purpose: Infections and vaccinations have been identified as potential immunological triggers of neuralgic amyotrophy (NA), but the exact type and frequency of the preceding agents is unknown. Methods: This was a multicentre, prospective, observational, matched case–control study. NA was diagnosed by neuromuscular experts according to validated clinical criteria and electrodiagnostic studies. Clinical data and biological samples of NA patients were collected within 90 days from disease onset between June 2018 and December 2023. All NA patients were asked about prior infection and vaccination in the month before disease onset. Serological tests for hepatitis E virus, human immunodeficiency virus, severe acute respiratory syndrome coronavirus 2, Epstein–Barr virus, cytomegalovirus, parvovirus B19, varicella‐zoster virus, Borrelia burgdorferi, Mycoplasma pneumoniae and Bartonella henselae were performed in a central laboratory. Each case was matched with a healthy control for age, sex, place of residence and time of blood collection. Results: Fifty‐seven patients and corresponding controls were included. The mean age was 45 years for both groups. NA onset was preceded by a symptomatic infectious trigger confirmed by microbiological tests in 15/57 (26.3%) patients. Coronavirus disease 2019 vaccination was considered a potential trigger in 7/57 (12.3%) subjects. An acute viral infection was associated with a bilateral involvement of the brachial plexus (p = 0.003, Cramèr's V = 0.43). Conclusions: Confirmed immune triggers (infection or vaccination) preceded disease onset in 22/57 (38.6%) NA cases. We suggest to test NA patients in the acute phase for intracellular antigens, especially in the case of concomitant bilateral involvement and hepatitis. [ABSTRACT FROM AUTHOR]

Background: Whey protein isolate (WPI) is a by-product from the dairy industry, whose main component is β-lactoglobulin. Upon heating, WPI forms a hydrogel which can both support controlled drug delivery and enhance the proliferation and osteogenic differentiation of bone-forming cells. This study makes a novel contribution by evaluating the ability of WPI hydrogels to support the growth of endothelial cells, which are essential for vascularization, which in turn is a pre-requisite for bone regeneration. Methods: In this study, the proliferation and antioxidant levels in human umbilical vascular endothelial cells (HUVECs) cultured with WPI supplementation were evaluated using real-time cell analysis and flow cytometry. Further, the attachment and growth of HUVECs seeded on WPI-based hydrogels with different concentrations of WPI (15%, 20%, 30%, 40%) were investigated. Results: Supplementation with WPI did not affect the viability or proliferation of HUVECs monitored with real-time cell analysis. At the highest used concentration of WPI (500 µg/mL), a slight induction of ROS production in HUVECs was detected as compared with control samples, but it was not accompanied by alterations in cellular thiol levels. Regarding WPI-based hydrogels, HUVEC adhered and spread on all samples, showing good metabolic activity. Notably, cell number was highest on samples containing 20% and 30% WPI. Conclusions: The demonstration of the good compatibility of WPI hydrogels with endothelial cells in these experiments is an important step towards promoting the vascularization of hydrogels upon implantation in vivo, which is expected to improve implant outcomes in the future.

Superparamagnetic iron oxide nanoparticles (SPION) are being investigated for many purposes, e.g., for the amplification of ionizing radiation and for the targeted application of therapeutics. Therefore, we investigated SPIONs coated with (3-Aminopropyle)-Triethoxysilane (SPION-APTES) for their influence on different head and neck squamous cell carcinoma (HNSCC) cell lines, as well as for their suitability as a radiosensitizer. We used 24-well microscopy and immunofluorescence microscopy for cell observation, growth curves to determine cytostatic effects, and colony formation assays to determine cytotoxicity. We found that the APTES-SPIONs were very well taken up by the HNSCC cells. They generally have a low cytotoxic effect, showing no significant difference in clonogenic survival between the control group and cells treated with 20 µg Fe/mL (p > 0.25) for all cell lines. They have a cytostatic effect on some cell lines cells (e.g., Cal33) that is visible across different radiation doses (1, 2, 8 Gy, p = 0.05). In Cal33, e.g., SPION-APTES raised the doubling time at 2 Gy from 24.53 h to 41.64 h. Importantly, these findings vary notably between the cell lines. However, they do not significantly alter the radiation effect: only one out of eight cell lines treated with SPION-APTES showed a significantly reduced clonogenic survival after ionizing radiation with 2 Gy, and only two showed significantly reduced doubling times. Thus, although the APTES-SPIONs do not qualify as a radiosensitizer, we were still able to vividly demonstrate and analyze the effect that the APTES-SPIONs have on various cell lines as a contribution to further functionalization.

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide. They are associated with alcohol and tobacco consumption, as well as infection with human papillomaviruses (HPV). Therapeutic options include radiochemotherapy, surgery or chemotherapy. Nanoparticles are becoming more and more important in medicine. They can be used diagnostically, but also therapeutically. In order to provide therapeutic alternatives in the treatment of HNSCC, the effect of citrate-coated superparamagnetic iron oxide nanoparticles (Citrate-SPIONs) and gold-coated superparamagnetic iron oxide nanoparticles (Au-SPIONs) in combination with ionizing irradiation (IR) on two HPV positive and two HPV negative HNSCC and healthy fibroblasts and keratinocytes cell lines were tested. Effects on apoptosis and necrosis were analyzed by using flow cytometry. Cell survival studies were performed with a colony formation assay. To better understand where the SPIONs interact, light microscopy images and immunofluorescence studies were performed. The HNSCC and healthy cell lines showed different responses to the investigated SPIONs. The cytotoxic effects of SPIONs, in combination with IR, are dependent on the type of SPIONs, the dose administered and the cell type treated. They are independent of HPV status. Reasons for the different cytotoxic effect are probably the different compositions of the SPIONs and the related different interaction of the SPIONs intracellularly and paramembranously, which lead to different strong formations of double strand breaks.

Dextran-coated superparamagnetic iron oxide nanoparticles (SPIONDex) of various sizes can be used as contrast agents in magnetic resonance imaging (MRI) of different tissues, e.g., liver or atherosclerotic plaques, after intravenous injection. In previous studies, the blood compatibility and the absence of immunogenicity of SPIONDex was demonstrated. The investigation of the interference of SPIONDex with stimulated immune cell activation is the aim of this study. For this purpose, sterile and endotoxin-free SPIONDex with different hydrodynamic sizes (30 and 80 nm) were investigated for their effect on monocytes, dendritic cells (DC) and lymphocytes in concentrations up to 200 µg/mL, which would be administered for use as an imaging agent. The cells were analyzed using flow cytometry and brightfield microscopy. We found that SPIONDex were hardly taken up by THP-1 monocytes and did not reduce cell viability. In the presence of SPIONDex, the phagocytosis of zymosan and E. coli by THP-1 was dose-dependently reduced. SPIONDex neither induced the maturation of DCs nor interfered with their stimulated maturation. The particles did not induce lymphocyte proliferation or interfere with lymphocyte proliferation after stimulation. Since SPIONDex rapidly distribute via the blood circulation in vivo, high concentrations were only reached locally at the injection site immediately after application and only for a very limited time. Thus, SPIONDex can be considered immune compatible in doses required for use as an MRI contrast agent.

Nanoformulations for delivering nucleotides into cells as vaccinations as well as treatment of various diseases have recently gained great attention. Applying such formulations for a local treatment strategy, e.g., for cancer therapy, is still a challenge, for which improved delivery concepts are needed. Hence, this work focuses on the synthesis of superparamagnetic iron oxide nanoparticles (SPIONs) for a prospective “magnetofection” application. By functionalizing SPIONs with an active catechol ester (CafPFP), polyethyleneimine (PEI) was covalently bound to their surface while preserving the desired nanosized particle properties with a hydrodynamic size of 86 nm. When complexed with plasmid-DNA (pDNA) up to a weight ratio of 2.5% pDNA/Fe, no significant changes in particle properties were observed, while 95% of the added pDNA was strongly bound to the SPION surface. The transfection in A375-M cells for 48 h with low amounts (10 ng) of pDNA, which carried a green fluorescent protein (GFP) sequence, resulted in a transfection efficiency of 3.5%. This value was found to be almost 3× higher compared to Lipofectamine (1.2%) for such low pDNA amounts. The pDNA-SPION system did not show cytotoxic effects on cells for the tested particle concentrations and incubation times. Through the possibility of additional covalent functionalization of the SPION surface as well as the PEI layer, Caf-PEI-SPIONs might be a promising candidate as a magnetofection agent in future.

Gram+ bacteria are very common in clinical medicine and responsible for a large number of infectious diseases. For example, Gram+ bacteria play a major role in causing bloodstream infections and sepsis. Therefore, the detection of Gram+ bacteria is of great importance for the diagnosis and treatment of infectious diseases. Furthermore, these bacteria are often present in biofilms that cover implants. Recent research work has mainly focused on the biologic activity and removal of Gram-negative bacteria or bacterial components such as lipopolysaccharides (LPS). In contrast, the effects of lipoteichoic acid (LTA) have been less well studied so the relevance of their removal from body fluids is possibly underestimated. To address this topic, we evaluated superparamagnetic iron oxide particles (SPION) carrying different peptides derived from the innate immune receptor (GP-340) for their ability to bind and remove Gram+ bacteria and LTA from different media. Our results show that, beyond S. aureus, effective agglutinating and removing of S. pneumoniae was possible. Furthermore, we were able to show for the first time that this was possible with LTA alone and that the magnetic removal of bacteria was also efficient under flow conditions. We also found that this method was able to capture Stapyhylococcus aureus from platelet concentrates, which can help to enhance the sensitivity of microbiological diagnostics, quality control measures, and blood product safety.

Objective: Inflammatory polyradiculomyelitis belongs to a rare group of immune-mediated diseases affecting both the central and peripheral nervous system. We aimed to describe an unusual presentation of acute polyradiculomyelitis with marked spinal cord lesions restricted to the gray matter.Methods: Thorough examination of two case reports including clinical, MRI, serologic, electrophysiologic and CSF examinations as well as short-term follow-up.Results: We present two adult patients with acute polyradiculomyelitis and unusual spinal cord lesions restricted to the gray matter on MRI. The clinical presentation, serologic, electrophysiologic and CSF features of the two patients varied, whereas both patients demonstrated severe, asymmetrical, predominantly distal, motor deficits of the lower extremities as well as bladder and bowel dysfunction. Both patients only partially responded to anti-inflammatory treatment. Severe motor impairment and bladder dysfunction persisted even months after symptom onset.Conclusions: To our best of knowledge, these are the first reports of acute polyradiculomyelitis with distinct involvement of the lower thoracic spinal cord gray matter. Currently, it remains unclear whether gray matter lesions reflect a separate pathophysiologic mechanism or an exceedingly rare presentation of spinal cord involvement in acute polyradiculomyelitis.

Background: Acute hepatitis E virus (HEV) infection has recently emerged as a potential trigger for acute dysimmune neuropathies, but prospective controlled studies are lacking. Aims: To compare the frequency of concomitant acute HEV infection in patients with neuralgic amyotrophy (NA), Guillain–Barré syndrome (GBS), and Bell's palsy with a matched control population. Methods: Swiss multicenter, prospective, observational, matched case–control study over 3 years (September 2019–October 2022). Neurological cases with NA, GBS, or Bell's palsy were recruited within 1 month of disease onset. Healthy controls were matched for age, sex, geographical location, and timing of blood collection. Diagnostic criteria for acute hepatitis E were reactive serum anti‐HEV IgM and IgG assays (ELISA test) and/or HEV RNA detection in serum by real‐time polymerase chain reaction (RT‐PCR). RT‐PCR was performed on sera to confirm IgM positivity. Results: We included 180 patients (59 GBS, 51 NA, 70 Bell's palsy cases) and corresponding matched controls (blood donors) with median age 51 years for both groups and equal gender distribution. Six IgM+ cases were detected in the NA, two in the GBS, and none in the Bell's palsy group. Two controls were anti‐HEV IgM‐positive. At disease onset, most cases with acute HEV infection had increased liver enzymes. A moderate association (p = 0.027, Fisher's exact test; Cramér's V = −0.25) was observed only between acute HEV infection and NA. Conclusion: This prospective observational study suggests an association between concomitant acute HEV infection and NA, but not with GBS or Bell's palsy. [ABSTRACT FROM AUTHOR]

Surface-functionalized gold-coated superparamagnetic iron oxide nanoparticles (Au-SPIONs) may be a useful tool in various biomedical applications. To obtain Au-SPIONs, gold salt was precipitated onto citrate-stabilized SPIONs (Cit-SPIONs) using a simple, aqueous one-pot technique inspired by the Turkevich method of gold nanoparticle synthesis. By the further stabilization of the Au-SPION surface with additional citrate (Cit-Au-SPIONs), controllable and reproducible Z-averages enhanced long-term dispersion stability and moderate dispersion pH values were achieved. The citrate concentration of the reaction solution and the gold/iron ratio was found to have a major influence on the particle characteristics. While the gold-coating reduced the saturation magnetization to 40.7% in comparison to pure Cit-SPIONs, the superparamagnetic behavior of Cit-Au-SPIONs was maintained. The formation of nanosized gold on the SPION surface was confirmed by X-ray diffraction measurements. Cit-Au-SPION concentrations of up to 100 µg Fe/mL for 48 h had no cytotoxic effect on Jurkat cells. At a particle concentration of 100 µg Fe/mL, Jurkat cells were found to take up Cit-Au-SPIONs after 24 h of incubation. A significantly higher attachment of thiol-containing L-cysteine to the particle surface was observed for Cit-Au-SPIONs (53%) in comparison to pure Cit-SPIONs (7%).

Urban road networks may benefit from left turn prohibition at signalized intersections regarding capacity, for particular traffic demand patterns. The objective of this paper is to propose a method for minimizing the total travel time by prohibiting left turns at intersections. With the flows obtained from the stochastic user equilibrium model, we were able to derive the stage generation, stage sequence, cycle length, and the green durations using a stage-based method which can handle the case that stages are sharing movements. The final output is a list of the prohibited left turns in the network and a new signal timing plan for every intersection. The optimal list of prohibited left turns was found using a genetic algorithm, and a combination of several algorithms was employed for the signal timing plan. The results show that left turn prohibition may lead to travel time reduction. Therefore, when designing a signal timing plan, left turn prohibition should be considered on a par with other left turn treatment options.