•Path planning in large dense grid-based automated guided vehicle systems.•Proposal and simulation of a real-time dynamic path planning approach.•Using a graph-based system representation with ...changing vertex weights over time.•Enabling deadlock recovery through re-planning over time.•Evaluation through discrete event simulations on four layouts for two AGV densities.
Real-time path planning for large, dense grid-based automated guided vehicle (AGV) systems, used for example to sort parcels, is challenging. Most approaches described in the literature are not fast enough for real-time control or are not able to avoid congestion. This paper presents a dynamic approach using a graph-representation of the grid system layout with vertex weights that are updated over time. By means of an extensive discrete-event simulation, we show that the proposed path planning approach significantly increases the throughput compared to existing approaches. Furthermore, it enables the recovery from deadlock situations.
The cytoskeleton is a highly adaptive network of filamentous proteins capable of stiffening under stress even as it dynamically assembles and disassembles with time constants of minutes. Synthetic ...materials that combine reversibility and strain-stiffening properties remain elusive. Here, strain-stiffening hydrogels that have dynamic fibrous polymers as their main structural components are reported. The fibers form via self-assembly of bolaamphiphiles (BA) in water and have a well-defined cross-section of 9 to 10 molecules. Fiber length recovery after sonication, H/D exchange experiments, and rheology confirm the dynamic nature of the fibers. Cross-linking of the fibers yields strain-stiffening, self-healing hydrogels that closely mimic the mechanics of biological networks, with mechanical properties that can be modulated by chemical modification of the components. Comparison of the supramolecular networks with covalently fixated networks shows that the noncovalent nature of the fibers limits the maximum stress that fibers can bear and, hence, limits the range of stiffening.
Local intraperitoneal drug administration is considered a challenging drug delivery route. The therapeutic efficiency is low, mainly due to rapid clearance of drugs. To increase the intraperitoneal ...retention time of specific drugs, a pH‐sensitive supramolecular hydrogel that can act as a drug delivery vehicle is developed. To establish the optimal formulation of the hydrogel and to study its feasibility, safety, and tissue compatibility, in vitro, postmortem, and in vivo experiments are performed. In vitro tests reveal that a hydrogelator formulation with pH ≥ 9 results in a constant viscosity of 0.1 Pa·s. After administration postmortem, the hydrogel covers the parietal and visceral peritoneum with a thin, soft layer. In the subsequent in vivo experiments, 14 healthy rats are subjected to intraperitoneal injection with the hydrogel. Fourteen and 28 days after implantation, the animals are euthanized. Intraperitoneal exposure to the hydrogel is not resulted in significant weight loss or discomfort. Moreover, no macroscopic adverse effects or signs of organ damage are detected. In several intra‐abdominal tissues, vacuolated macrophages are found indicating a physiological degradation of the synthetic hydrogel. This study demonstrates that the supramolecular hydrogel is safe for intraperitoneal application and that the hydrogel shows good tissue compatibility in rats.
Several in vitro and postmortem tests are conducted to establish an optimal hydrogel formulation specifically for the intraperitoneal application. Subsequent in vivo experiments demonstrate the feasibility, safety, and tissue compatibility of the intraperitoneal administration of a pH‐sensitive supramolecular hydrogel in 14 healthy rats. No significant weight loss or discomfort, macroscopic adverse effects, or signs of organ damage are found.
Grounded in the Cognitive Evaluation Theory, a mini‐theory of Self‐Determination Theory, this experimental field study sought to examine the impact of competence support of both coaches and athlete ...leaders on athletes’ competence satisfaction, intrinsic motivation, and subjective as well as objective performance. Male basketball players (N = 120) were allocated to groups of 5 players. These groups were then randomly assigned to a control group or to 1 of 3 experimental conditions. In these experimental conditions, either the coach, the athlete leader, or both provided motivational feedback to their team. The provision of motivational feedback by either the coach or the athlete leader was sufficient to increase athletes’ competence satisfaction, intrinsic motivation, and objective performance (i.e., enhanced execution time without a decrease in scoring percentage) relative to the control group. Interestingly, when both the coach and the athlete leader provided competence support, a surplus effect was observed on objective performance compared with when only the coach provided competence support. Furthermore, structural equation modeling revealed that players’ competence satisfaction mediated the relationship between the provided competence support and players’ intrinsic motivation, while a direct effect was observed on objective performance. In conclusion, the study findings indicate that also athlete leaders can adopt a motivating role, and that by doing so, their impact is as strong as the impact of the coach. Both coaches and athlete leaders can thus boost athletes’ objective performance and foster competence satisfaction, with the latter resulting in increased intrinsic motivation.
Treatment of cancer in the peritoneal cavity may be improved with macroscale drug delivery systems that offer control over intraperitoneal concentration of chemotherapeutic agents. Currently, ...suitable drug carriers to facilitate a sustained release of small hydrophilic drugs such as mitomycin C are lacking. For this purpose, a pH‐responsive supramolecular hydrogel based on ureido‐pyrimidinone (UPy) chemistry is utilized here. In order to provide a sustained release profile, a lipophilicity‐increasing cholesterol conjugation strategy is proposed that enhances affinity between the modified drug (mitomycin‐PEG24‐cholesterol, MPC) and the hydrophobic compartments in the UPy gel. Additional advantages of cholesterol conjugation include improved chemical stability and potency of mitomycin C. In vitro the tunability of the system to obtain optimal effective concentrations over time is demonstrated with a combinatorial treatment of mitomycin C and MPC in one UPy hydrogel delivery system.
Hydrophilic chemotherapeutic mitomycin C is modified with a cholesterol group. This modification improves potency, prevents chemical degradation, and radically enhances retention in a supramolecular ureido‐pyrimidinone hydrogel. A sustained release and a prolonged effect in vitro are hereby realized. To maximize therapeutic effect, the new drug can be combined with parent mitomycin C in one hydrogel system.
The present research examines the impact of leaders' confidence in their team on the team confidence and performance of their teammates. In an experiment involving newly assembled soccer teams, we ...manipulated the team confidence expressed by the team leader (high vs neutral vs low) and assessed team members' responses and performance as they unfolded during a competition (i.e., in a first baseline session and a second test session). Our findings pointed to team confidence contagion such that when the leader had expressed high (rather than neutral or low) team confidence, team members perceived their team to be more efficacious and were more confident in the team's ability to win. Moreover, leaders' team confidence affected individual and team performance such that teams led by a highly confident leader performed better than those led by a less confident leader. Finally, the results supported a hypothesized mediational model in showing that the effect of leaders' confidence on team members' team confidence and performance was mediated by the leader's perceived identity leadership and members' team identification. In conclusion, the findings of this experiment suggest that leaders' team confidence can enhance members' team confidence and performance by fostering members' identification with the team.
Colorectal cancer is a multi-step process characterized by a sequence of genetic alterations in cell growth regulatory genes, such as the adenomatous polyposis coli, KRAS, p53 and DCC genes. In the ...present study mutation analysis was performed with SSCA/direct sequencing of the hot-spot regions in exons 11 and 15 for the BRAF gene and exons 1–2 for the KRAS gene in 130 primary colorectal cancer tumors and correlated with clinico-pathological and mutational data. We also performed mutation analysis of the corresponding conserved regions in the ARAF and RAF-1 genes. Mutations in the BRAF and KRAS genes were found in 11.5 and 40% of the tumors, respectively. One germline exonic and nine germline intronic genetic variants were found in the ARAF and RAF-1 genes. All of the BRAF mutations were located in the kinase domain of the conserved region 3 in exon 15 of the BRAF gene. One novel somatic mutation was also identified in the BRAF gene. The majority of the BRAF mutations were found in colon compared with rectal tumors (P = 0.014). In agreement with others, a statistically significant correlation between BRAF mutations and microsatellite instability could be found. A negative correlation was also evident between mutations in the BRAF and KRAS genes, which supports earlier studies where somatic mutations in these genes are mutually exclusive. Collectively, our results provide support for the idea that activation of the MAP kinase pathway, especially via BRAF and KRAS mutations, is of critical importance for the development of colorectal cancer.
The performance was assessed of a new, rapid, visual and qualitative immunoassay for the detection of HIV p24 antigen (Ag) and antibodies (Ab) to HIV-1 and HIV-2. Characterised serum or plasma ...specimens from patients diagnosed with HIV infection were tested: 179 samples of known Ab-positive patients harbouring different subtypes of HIV-1 (
n
=
154) and HIV-2 (
n
=
25) and 200 samples from individuals not infected with HIV. The assay's Ag sensitivity was assessed by testing HIV seroconversion panels (
n
=
10) and primary HIV infection specimens (
n
=
57). In addition, the influence of the genetic variability of HIV-1 on Ag detection was evaluated using dilutions of culture supernatants infected with different subtypes (
n
=
50). The performance of the rapid test was compared to a “gold standard” testing algorithm with the use of a single Ag ELISA and with the Vironostika
® HIV Uni-Form II Ag/Ab test, a fourth-generation ELISA. The new assay, the Determine™ HIV-1/2 Combo demonstrated 100% (98.2–100.0) Ab specificity (200/200) and 100% (98.0–100.0) Ab sensitivity (179/179). In these samples, the observed Ag sensitivity was 86.6% (58/67) with the Determine™ HIV-1/2 Combo test and 92.5% (62/67) with the Vironostika compared to the reference single Ag ELISA. The assay could not detect Ag in one group O, one subtype F and two subtype H cell supernatant isolates. None of the HIV-2 Ag could be detected.
Objectives: To assess whether social capital benefits older adults’ self-rated health and well-being and whether physical activity mediates this relation. Methods: A survey study was conducted among ...members of a sociocultural organization (age ≥55 years), both cross-sectionally (baseline Time 1; N = 959) and longitudinally (3-year follow-up Time 2; N = 409). Results: Specific indicators of social capital were positively, though modestly, related to health and well-being at Time 1 and Time 2. Experienced connectedness with age peers emerged as the strongest predictor. Physical activity only mediated the relation with experienced safety in society. Discussion: The relative importance of older adults’ experienced connectedness with their age peers underlines the importance of internalized group membership as a determinant of their health and well-being. Physical activity seems to play only a minor mediating role.
The prognosis of colorectal cancer patients with peritoneal metastases is very poor. Intraperitoneal drug delivery systems, like supramolecular hydrogels, are being developed to improve local ...delivery and intraperitoneal residence time of a cytostatic such as mitomycin C (MMC). In this study, we evaluate the effect of intraperitoneal hydrogel administration on anastomotic healing. Forty-two healthy Wistar rats received a colonic end-to-end anastomosis, after which 6 animals received an intraperitoneal injection with saline, 18 with unloaded hydrogel and 18 with MMC-loaded hydrogel. After 7 days, animals were euthanized, and the anastomotic adhesion and leakage score were measured as primary outcome. Secondary outcomes were bursting pressure, histological anastomosis evaluation and body weight changes. Twenty-two rats completed the follow-up period (saline: n = 6, unloaded hydrogel: n = 10, MMC-loaded hydrogel: n = 6) and were included in the analysis. A trend towards significance was found for anastomotic leakage score between the rats receiving saline and unloaded hydrogel after multiple-comparison correction (p = 0.020, α = 0.0167). No significant differences were found for all other outcomes. The main reason for drop-out in this study was intestinal blood loss. Although the preliminary results suggest that MMC-loaded or unloaded hydrogel does not influence anastomotic healing, the intestinal blood loss observed in a considerable number of animals receiving unloaded and MMC-loaded hydrogel implies that the injection of the hydrogel under the studied conditions is not safe in the current rodent model and warrants further optimalisation of the hydrogel.
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