Search Results (17)

Background and aims: Brain metastases are prevalent in the late stages of malignant melanoma. Multimodal therapy remains challenging. Patient-derived organoids (PDOs) represent a valuable pre-clinical model, faithfully recapitulating key aspects of the original tumor, including the heterogeneity and the mutational status. This study aimed to establish PDOs from melanoma brain metastases (MBM-PDOs) and to test the feasibility of using them as a model for in vitro targeted-therapy drug testing. Methods: Surgical resection samples from eight patients with melanoma brain metastases were used to establish MBM-PDOs. The samples were enzymatically dissociated followed by seeding into low-attachment plates to generate floating organoids. The MBM-PDOs were characterized genetically, histologically, and immunohistologically and compared with the parental tissue. The MBM-PDO cultures were exposed to dabrafenib (BRAF inhibitor) and trametinib (MEK inhibitor) followed by a cell viability assessment. Results: Seven out of eight cases were successfully cultivated, maintaining the histological, immunohistological phenotype, and the mutational status of the parental tumors. Five out of seven cases harbored BRAF V600E mutations and were responsive to BRAF and MEK inhibitors in vitro. Two out of seven cases were BRAF wild type: one case harboring an NRAS mutation and the other harboring a KIT mutation, and both were resistant to BRAF and MEK inhibitor therapy. Conclusions: We successfully established PDOs from melanoma brain metastases surgical specimens, which exhibited a consistent histological and mutational profile with the parental tissue. Using FDA-approved BRAF and MEK inhibitors, our data demonstrate the feasibility of employing MBM-PDOs for targeted-therapy in vitro testing. Full article

This paper presents the parallelization of two widely used implicit numerical solvers for the solution of partial differential equations on structured meshes, namely, the ADI (Alternating-Direction Implicit) solver for tridiagonal linear systems and the SIP (Strongly Implicit Procedure) solver for the penta-diagonal systems. Both solvers were parallelized using CUDA (Computer Unified Device Architecture) Fortran on GPGPUs (General-Purpose Graphics Processing Units). The parallel ADI solver (P-ADI) is based on the Parallel Cyclic Reduction (PCR) algorithm, while the parallel SIP solver (P-SIP) uses the wave front method (WF) following a diagonal line calculation strategy. To map the solution schemes onto the hierarchical block-threads framework of the CUDA on the GPU, the P-ADI solver adopted two mapping methods, one block thread with iterations (OBM-it) and multi-block threads (MBMs), while the P-SIP solver also used two mappings, one conventional mapping using effective WF lines (WF-e) with matrix coefficients and solution variables defined on original computational mesh, and a newly proposed mapping using all WF mesh (WF-all), on which matrix coefficients and solution variables are defined. Both the P-ADI and the P-SIP have been integrated into a two-dimensional (2D) hydrodynamic model, the CCHE2D (Center of Computational Hydroscience and Engineering) model, developed by the National Center for Computational Hydroscience and Engineering at the University of Mississippi. This study for the first time compared these two parallel solvers and their efficiency using examples and applications in complex geometries, which can provide valuable guidance for future uses of these two parallel implicit solvers in computational fluids dynamics (CFD). Both parallel solvers demonstrated higher efficiency than their serial counterparts on the CPU (Central Processing Unit): 3.73~4.98 speedup ratio for flow simulations, and 2.166~3.648 speedup ratio for sediment transport simulations. In general, the P-ADI solver is faster than but not as stable as the P-SIP solver; and for the P-SIP solver, the newly developed mapping method WF-all significantly improved the conventional mapping method WF-e. Full article

Organic waste can provide an alternative to synthetic fertilisers for maintaining productivity with limited environmental impact. Our research evaluates the potential use of processed animal waste in corn fertilisation, which may represent a partially closed nutrient cycle of importance in a sustainable agricultural system. The objective of this study was to evaluate the quantity and quality of fat obtained from corn grain fertilised with meat and bone meal (MBM) produced from animal waste. A static field experiment using MBM was conducted at the Experimental Station in Tomaszkowo (53°71′ N, 20°43′ E), Poland. The field experiment was conducted in 2014–2017 with continuous corn cultivation. The course of weather conditions in the years of this study influenced the fat content, with the lowest amount found in 2016. The application of fertilisers in the form of MBM and mineral fertilisation resulted in a slightly lower fat content compared to the variant without fertilisation. The application of mineral fertilisers and MBM influenced an increase in the content of the predominant C18:2 acid compared to the variant without fertilisation, while the opposite was shown for C18:1 cis-9 acid. The fertiliser variants are most correlated with fat yield and total polyunsaturated fatty acids. The fertiliser variants in their effects on fat yield, fat content, fatty acid profiles, and their ratios can be divided into three groups, which were related to the effects of organic fertilisers during the years of this study. The use of meat and bone meal as fertilisers cannot be regarded as a factor in increasing the fat content of corn grain. Meat and bone meal applied over several years to the same field in the quantities required to achieve optimum yield can be an element that shapes fatty acid profiles. Full article

After recognizing the importance of marine and coastal resources and the use of marine space for economic growth, the European Union (EU) created and implemented a long-term Blue Economy (BE) strategy that supports the development of traditional and emerging marine and maritime sectors, aiming at the enhancement of Blue Growth (BG). However, despite the existence of a robust policy framework that supports the expansion of BE sectors at both an EU Sea Basin and state level, scholars have been sceptical as to whether the pursuit of BG adequately addresses the challenges that usually come with economic development, including those of climate change and marine biodiversity loss. Various frameworks for integrating sectoral goals with each other and with environmental goals that could facilitate the transition towards Sustainable Blue Growth (SBG) already exist and have been suggested and promoted by the European Commission, such as Ecosystem-Based Management (EBM) and Marine Spatial Planning (MSP). They require the consideration of marine ecosystems and biodiversity and their protection as one of the BE sectors to be integrated via planning and management, which in turn requires the estimation of the value of ecosystem services and the spatial implications thereof. Nonetheless, there is little evidence or real-world examples on whether and how ecosystems, and within them coastal and marine biodiversity, are actually integrated (i.e., mainstreamed) when developing sectoral policies and planning and implementing economic activities at sea at various scales, i.e., local, national, and regional, and what the necessary steps and actions are that would facilitate such mainstreaming. By seeking evidence in EU and Atlantic Arc (AA) member states’ sectoral policies on marine tourism, ports and shipping, marine renewable energy, and fisheries and aquaculture (as promoted by the Atlantic Maritime Strategy and its corresponding action plans) and in the outcomes of the Interreg Atlantic Funded Research Project MOSES (aiming at valuating a Sustainable Blue Economy at the national and regional scale of the EU AA), the present article focused on understanding if and how marine biodiversity is taken into consideration by EU and AA BE and/or BG policies, strategies, and sectoral developments. Τhe selected sectoral policies demonstrate a good uptake of marine-ecosystem- and biodiversity-related challenges; however, at both the EU and the AA member-state level, it is unclear whether and how marine ecosystems and biodiversity are addressed as a separate BE sector. As such, we argue why and how Marine Biodiversity Mainstreaming (MBM) could address this gap, and hence it could contribute to planning, implementing, and managing maritime economic activities towards SBG at the Sea Basin level. This is demonstrated by illustrating the central role of MBM in enabling (and being further enabled by) the above integrative frameworks (i.e., MSP and EBM) and by presenting the key elements and actions required for such facilitation. Full article

A hydride of Yb₂Pd₂Sn could be synthesized with approximately 2 H atoms per f.u. The hydrogenation leads to a volume expansion while preserving the tetragonal symmetry (P4/mbm). The lattice reaction is strongly anisotropic, and the 5% expansion in c is partly compensated by the 0.5% compression in a. The hydride is paramagnetic at least down to 0.5 K. Yb remains at or very close to the 3+ (4f¹³) state, as in Yb₂Pd₂Sn. Specific heat C/T vs. T shows an upturn existing already in Yb₂Pd₂Sn, but it is much more pronounced in the hydride (1.8 J/mol f.u. K² for T → 0, i.e., more than twice higher than in its precursor). This is interpreted as lowering the Kondo temperature due to H bonding. Full article

Meat and bone meal (MBM) is a product of the rendering industry, which is looking for high-value applications of rendered animal proteins (RAP). The objective of this research was to utilize MBM as a nitrogen source to produce astaxanthin (AX) by Xanthophyllomyces dendrorhous and quantify the bioavailability of MBM as a potential substitution of commercial nitrogen sources (i.e., yeast extract and peptone). To conduct yeast fermentation under the optimal glucose loading, the C/N ratio was optimized to achieve maximum AX content. MBM was hydrolyzed by using proteinase and alkaline (Ca(OH)₂) for 4, 8, and 16 h with different enzyme and alkaline loadings to produce MBM hydrolysates (MBMHs). The MBMHs were directly fermented by X. dendrorhous under the optimum glucose concentration. Experimentally, the optimum medium contained 40 g/L glucose, 5 g/L peptone, and 3 g/L yeast extract, where AX content of 3.69 mg/g dry cell mass was achieved. MBMHs were used by X. dendrorhous as a nitrogen source, while fermentation with lyophilized MBMHs was generated using proteinase K. This resulted in a maximum AX content of 1.58 mg/g dry cell mass. This research exhibits the feasibility of using MBM as a nitrogen source to produce AX with X. dendrorhous. Full article

Stage IV melanoma patients develop melanoma brain metastases (MBM) in 50% of cases. Their prognosis is improving, and its understanding outside the context of clinical trials is relevant. We have retrospectively analyzed the clinical data, course of treatment, and outcomes of 531 subsequent stage IV melanoma patients with BM treated in five reference Italian and Polish melanoma centers between 2014 and 2021. Patients with MBM after 2017 had a better prognosis, with a significantly improved median of overall survival (OS) after 2017 in the worst mol-GPA prognostic groups (mol-GPA ≤ 2): a median OS >6 months and HR 0.76 vs. those treated before 2017 (CI: 0.60–0.97, p = 0.027). In our prognostic model, mol-GPA was highly predictive for survival, and symptoms without steroid use did not have prognostic significance. Local therapy significantly improved survival regardless of the year of diagnosis (treated before or after 2017), with median survival >12 months. Systemic therapy improved outcomes when it was combined with local therapy. Local surgery was associated with improved OS regardless of the timing related to treatment start (i.e., before or after 30 days from MBM diagnosis). Local and systemic treatment significantly prolong survival for the poorest mol-GPA prognosis. Use of modern treatment modalities is justified in all mol-GPA prognostic groups. Full article

Electromagnetic bi-directional micropumps (EMBM) are indispensable for the development of portable devices which enable fluid transportation in forward and reverse directions. However, the high disposal cost of rare-earth magnets attached to the fluidic part and the low pump density due to multiple motors limit their practical application in disposable multi-channel microfluidic applications such as droplet-based oscillatory-flow (DBOF) rapid PCR amplification. Therefore, this paper presented a low-cost, disposable, high-pump-density EMBM. To reduce the disposal cost, we separated the magnets from the disposable fluidic part and used cylindrical holes to store and guide the magnet, which resulted in the ability to reuse all the magnets. To increase the pump density, we used the combination of one motor and one multi-pole ring magnet to drive several channels simultaneously. A proof-of-concept prototype with a pump density of 0.28 cm⁻² was fabricated and experimentally evaluated. The fabricated micropump exhibited a maximum flow rate of 0.86 mL/min and a maximum backpressure of 0.5 kPa at a resonant frequency around 50 Hz. The developed multi-channel micropump with reusable magnets is highly beneficial to the development of low-cost and high-throughput rapid PCR amplification microchips and therefore can have a significant impact on timely infectious disease recognition and intervention. Full article

The COVID-19 pandemic has affected the world socially and economically changing behaviors towards medical facilities, public gatherings, workplaces, and education. Educational institutes have been shutdown sporadically across the globe forcing teachers and students to adopt distance learning techniques. Due to the closure of educational institutes, work and learn from home methods have burdened the network resources and considerably decreased a viewer’s Quality of Experience (QoE). The situation calls for innovative techniques to handle the surging load of video traffic on cellular networks. In the scenario of distance learning, there is ample opportunity to realize multi-cast delivery instead of a conventional unicast. However, the existing 5G architecture does not support service-less multi-cast. In this article, we advance the case of Virtual Network Function (VNF) based service-less architecture for video multicast. Multicasting a video session for distance learning significantly lowers the burden on core and Radio Access Networks (RAN) as demonstrated by evaluation over a real-world dataset. We debate the role of Edge Intelligence (EI) for enabling multicast and edge caching for distance learning to complement the performance of the proposed VNF architecture. EI offers the determination of users that are part of a multicast session based on location, session, and cell information. Moreover, user preferences and network’s contextual information can differentiate between live and cached access patterns optimizing edge caching decisions. While exploring the opportunities of EI-enabled distance learning, we demonstrate a significant reduction in network operator resource utilization and an increase in user QoE for VNF based multicast transmission. Full article

The crystal structure, mechanical anisotropy, elastic properties and electronic characteristics, as well as the stability, of P4/m BN are predicted by means of density functional theory. In this work, BN in the P4/m phase demonstrates mechanical and dynamical stability. Compared with the values of bulk B, E and G in the P4/m phase, the B of BN in the P4/m phase is greater than that of dz4 BN, while the G and E of P4/m BN are greater than those of Pnc2 BN and dz4 BN. The ratio of the bulk-to-shear modulus for P4/m BN is less than 1.75 and dz4 BN, dz2 BN and lzlz2 BN, indicating that P4/m BN is more brittle than dz4 BN, dz2 BN and lzlz2 BN. P4/m BN exhibits stronger mechanical anisotropy in G and E than Pbca BN, P4₂/mnm BN and Pm-3m BN but much weaker mechanical anisotropy than P4/mbm BN, B₇N₇, B₁₁N₁₁ and B₁₅N₁₅. In addition, P4/m BN is a quasi-direct bandgap semiconductor, and the difference between the direct and the indirect bandgap is 0.008 eV. In order to obtain further characteristics of P4/m BN for future synthetic verification, the X-ray diffraction (XRD) patterns for P4/m BN are also calculated. Given its properties, P4/m BN is a good candidate for photoelectric devices. Full article

This study demonstrates the utility of an updated mass balance model for predicting the distribution of organic chemicals in in vitro test systems (IV-MBM EQP v2.0) and evaluates its performance with empirical data. The IV-MBM EQP v2.0 tool was parameterized and applied to four independent data sets with measured ratios of bulk medium or freely-dissolved to initial nominal concentrations (e.g., C24/C0 where C24 is the measured concentration after 24 h of exposure and C0 is the initial nominal concentration). Model performance varied depending on the data set, chemical properties (e.g., “volatiles” vs. “non-volatiles”, neutral vs. ionizable organics), and model assumptions but overall is deemed acceptable. For example, the r² was greater than 0.8 and the mean absolute error (MAE) in the predictions was less than a factor of two for most neutral organics included. Model performance was not as good for the ionizable organic chemicals included but the r² was still greater than 0.7 and the MAE less than a factor of three. The IV-MBM EQP v2.0 model was subsequently applied to several hundred chemicals on Canada’s Domestic Substances List (DSL) with nominal effects data (AC50s) reported for two in vitro assays. We report the frequency of chemicals with AC50s corresponding to predicted cell membrane concentrations in the baseline toxicity range (i.e., >20–60 mM) and tabulate the number of chemicals with “volatility issues” (majority of chemical in headspace) and “solubility issues” (freely-dissolved concentration greater than water solubility after distribution). In addition, the predicted “equivalent EQP blood concentrations” (i.e., blood concentration at equilibrium with predicted cellular concentration) were compared to the AC50s as a function of hydrophobicity (log octanol-water partition or distribution ratio). The predicted equivalent EQP blood concentrations exceed the AC50 by up to a factor of 100 depending on hydrophobicity and assay conditions. The implications of using AC50s as direct surrogates for human blood concentrations when estimating the oral equivalent doses using a toxicokinetic model (i.e., reverse dosimetry) are then briefly discussed. Full article

Existing technologies in disaster and safety communication networks (DSCNs) face problems such as narrow bandwidth, low transmission rate, and difficulty in securing channels. Conversely, public safety long-term evolution (PS-LTE) technology provides high-speed, low-latency, quick-setup, and high-security data access for multimedia-based mission-critical services. To perform tests on each unit of core equipment with PS-LTE technology, a new call model such as push-to-talk, which is a service representing PS-LTE, is required. Moreover, objective and consistent metrics and methods are required for administering tests on the unique functions of DSCNs newly constructed with PS-LTE technology. This paper proposes a call model for the core facilities of DSCNs established in Korea, and it also suggests test and verification methods for all the areas of PS-LTE, including mission-critical push-to-talk, evolved multimedia broadcast and multicast service, and coverage and quality assessment for wireless services. Full article

High-throughput analysis of biomass is necessary to ensure consistent and uniform feedstocks for agricultural and bioenergy applications and is needed to inform genomics and systems biology models. Pyrolysis followed by mass spectrometry such as molecular beam mass spectrometry (py-MBMS) analyses are becoming increasingly popular for the rapid analysis of biomass cell wall composition and typically require the use of different data analysis tools depending on the need and application. Here, the authors report the py-MBMS analysis of several types of lignocellulosic biomass to gain an understanding of spectral patterns and variation with associated biomass composition and use machine learning approaches to classify, differentiate, and predict biomass types on the basis of py-MBMS spectra. Py-MBMS spectra were also corrected for instrumental variance using generalized linear modeling (GLM) based on the use of select ions relative abundances as spike-in controls. Machine learning classification algorithms e.g., random forest, k-nearest neighbor, decision tree, Gaussian Naïve Bayes, gradient boosting, and multilayer perceptron classifiers were used. The k-nearest neighbors (k-NN) classifier generally performed the best for classifications using raw spectral data, and the decision tree classifier performed the worst. After normalization of spectra to account for instrumental variance, all the classifiers had comparable and generally acceptable performance for predicting the biomass types, although the k-NN and decision tree classifiers were not as accurate for prediction of specific sample types. Gaussian Naïve Bayes (GNB) and extreme gradient boosting (XGB) classifiers performed better than the k-NN and the decision tree classifiers for the prediction of biomass mixtures. The data analysis workflow reported here could be applied and extended for comparison of biomass samples of varying types, species, phenotypes, and/or genotypes or subjected to different treatments, environments, etc. to further elucidate the sources of spectral variance, patterns, and to infer compositional information based on spectral analysis, particularly for analysis of data without a priori knowledge of the feedstock composition or identity. Full article

The search for life on Mars is predicated on the idea that Earth and Mars life (if present) should be both carbon- and water-based with similar forms of evolution. However, the astrobiology community can currently only investigate plausible Martian microbial ecosystems by using Terran life-forms as proxies. In order to examine how life might persist on Mars, we used a hypopiezotolerant bacterium (def., able to grow at 7–10 hPa)—Serratia liquefaciens—in growth assays with four Mars analog soils conducted under a subset of simulated Martian conditions including 7 hPa, 0 °C, and a CO₂-enriched anoxic atmosphere (called low-PTA conditions). The four Mars analog soils included an Aeolian dust analog, the Mars JSC-1 analog, a Phoenix lander-site simulant, and a high-Salts analog. Serratia liquefaciens cells were able to grow at 30 °C in a liquid minimal basal medium (MBM) supplemented with 10- or 20-mM sucrose, Spizizen salts, and micronutrients. When the four analog soils were doped with both MBM and cells of S. liquefaciens, and subsequently incubated at 30 °C for 72 h, cell densities increased between 2-logs (Phoenix analog) and 4-logs (Aeolian and JSC-1 analogs); the Salts analog led to complete inactivation of S. liquefaciens within 24 h. In contrast, when the experiment was repeated, but incubated under low-PTA conditions, S. liquefaciens cells were either killed immediately by the Salts analog, or decreased by >5 logs over 28 d by the Aeolian, JSC-1, and Phoenix analogs. The failure of S. liquefaciens to grow in the analog soils under low-PTA conditions was attributed to the synergistic interactions among six factors (i.e., low pressure, low temperature, anoxic atmosphere (i.e., the low-PTA conditions), low-pH in the Salts soil, dissolved salts in all analogs, and oligotrophic conditions) that increased the biocidal or inhibitory conditions within the analog soils. Results suggest that even if a hypopiezotolerant Terran microbe is displaced from a spacecraft surface on Mars, and lands in a hydrated and nutrient-rich niche, growth in the Martian regolith is not automatically assured. Full article

Collagen from a marine resource is believed to have more potential activity in bone tissue engineering and their bioactivity depends on biochemical and structural properties. Considering the above concept, pepsin soluble collagen (PSC) and acid soluble collagen (ASC) from blue shark (Prionace glauca) skin were extracted and its biochemical and osteogenic properties were investigated. The hydroxyproline content was higher in PSC than ASC and the purified collagens contained three distinct bands α₁, α_2, and β dimer. The purity of collagen was confirmed by the RP-HPLC profile and the thermogravimetric data showed a two-step thermal degradation pattern. ASC had a sharp decline in viscosity at 20–30 °C. Scanning electron microscope (SEM) images revealed the fibrillar network structure of collagens. Proliferation rates of the differentiated mouse bone marrow-mesenchymal stem (dMBMS) and differentiated osteoblastic (dMC3T3E1) cells were increased in collagen treated groups rather than the controls and the effect was dose-dependent, which was further supported by higher osteogenic protein and mRNA expression in collagen treated bone cells. Among two collagens, PSC had significantly increased dMBMS cell proliferation and this was materialized through increasing RUNX2 and collagen-I expression in bone cells. Accordingly, the collagens from blue shark skin with excellent biochemical and osteogenic properties could be a suitable biomaterial for therapeutic application. Full article