Endotoxins are considered as the major contributors to the pyrogenic response observed with contaminated pharmaceutical products. Recombinant biopharmaceutical products are manufactured using living organisms, including gram-negative bacteria. Upon the death of a gram-negative bacteria, endotoxins (also known as lipopolysaccharides; LPS) in the outer cell membrane are released into the lysate where it can interact with and form bonds with biomolecules, including target therapeutic compounds. Endotoxin contamination of biologic products may also occur through water, raw materials such as excipients, media, additives, sera, equipment, containers closure systems, and expression systems used in manufacturing. The manufacturing process is therefore in critical need to reduce and remove endotoxins by monitoring raw materials and in-process intermediates at critical steps, in addition to final drug product release testing. In this review, a discussion regarding the progression of endotoxin detection techniques, from crude to refined are presented. We provide a brief overview of the upstream processed used to manufacture therapeutic products and then discuss various downstream purification techniques widely used to purify the products off endotoxins. Finally, we investigate the effectiveness of endotoxin purification processes, both from a perspective of precision as well as cost-effectiveness.

Mannitol, a hyperosmotic agent, is commonly used in hemodialysis for eliminating the symptoms of dialysis disequilibrium syndrome. Mannitol extravasation is a potential complication which will induce fluid shift out of vessel, thrombophlebitis, bullous eruption and even compartment syndrome. We reported a case of mannitol extravasation due to improper mannitol infusion site during first hemodialysis.

Drug resistance is a great challenge in cancer therapy using chemotherapeutic agents. Administration of these drugs with siRNA is an efficacious strategy in this battle. Here, it was tried to incorporate siRNA and paclitaxel simultaneously into a novel nanocarrier. The selectivity of carrier to target cancer tissues was optimized through conjugation of folic acid (FA) and glucose onto its surface. The structure of nanocarrier formed from ternary magnetic copolymers based on FeCo-polyethylenimine (FeCo-PEI) nanoparticles and polylactic acid-polyethylene glycol (PLA-PEG) gene delivery system. Biocompatibility of FeCo-PEI-PLA-PEG-FA(NPsA), FeCo-PEI-PLA-PEG-Glu (NPsB) and FeCo-PEI-PLA-PEG-FA/Glu (NPsAB) nanoparticles and also influence of PTX-loaded nanoparticles on in vitro cytotoxicity were examined using MTT assay. Besides, siRNA-FAM internalization was investigated by fluorescence microscopy. The results showed the blank nanoparticles were significantly less cytotoxic at various concentrations. Meanwhile, siRNA-FAM/PTX encapsulated nanoparticles exhibited greater cytotoxicity on MCF-7 cells. NPsAB/siRNA/PTX nanoparticles showed greater effect on MCF-7 cell viability than NPsA/siRNA/PTX and NPsB/siRNA/PTX. Also, they induced significantly higher cytotoxic effects on cancer cells compared with NPsA/siRNA/PTX and NPsB/siRNA/PTX due to their multi-targeted properties using folic acid and glucose. We concluded that NPsAB nanoparticles have great potential for co-delivery of both drugs and genes for use in gene therapy and chemotherapy.

Rainfall derived infiltration and inflow (RDII) are extraneous water in a sanitary sewer system that are originated from rainfall in a surface runoff form. Most RDII enters sanitary sewer systems through illegal connections or mechanical faults especially in aged sewer systems. In this study, the physical process of three major RDII sources: roof downspout, sump pump, and leaky lateral, are investigated using physics-based models. These three sources represent three different flow paths: direct connection of impervious catchments, mixed flow through course porous media followed by a direct connection, and percolated flow through compacted soil, respectively. Due to the differences in medium and the flow paths, flow responses of these three RDII sources differ in time and magnitude and they can be distinctly identified from each other. The typical flow response of each RDII source is represented as an Impulse Response Function (IRF) that is a flow response to a pre-specified representative rainfall computed using physics-based models. The total RDII flow hydrograph is presented as a combination of these three IRFs and the weighting factors of each IRF is calibrated using a genetic algorithm (GA) technique in a test sewer catchment. The results may shed light on identifying the contributions of different RDII sources in a sewershed and help public water managers to better understand the local RDII issues which in turn facilitates a more effective management of a sewer system.

This paper applied ab initio theoretical studies on the complex of the π bond in C2H2 and nHX(n=1 8;X=F,Cl,Br,I),formed by typical X-H···π bond complexes in geometry and energy system is described and analysed,the results demonstrated that,C2H2···nHX(n=1 8;X=F,Cl,Br,I), with increasing halogen atomic number,from HF to HI,when hydrogen halide with the same number,the complex system of X-H···π bond length and other parameters showed a periodic increase;however,with the increase of the number of hydrogen halides,the binding energy of complex with n≤6,present in the overall increasing trend;and when n=6 reaches the maximum,in this case the π bond in C2H2 with hydrogen halide maximum capacity the limit has been reached, indicating that the π bond of C2H2···(HX)n up to six hydrogen halide molecules interactions to the formation of X-H···π bond complexes,that is to say X-H···π bond in C2H2···nHX complex have saturation property,and in the n=6 reach saturation state.

Humans currently occupy all continents and by doing so, modify the environment and create novel threats to many species; a phenomenon known as human-induced rapid environmental changes (HIREC). These growing anthropogenic disturbances represent major and relatively new environmental challenges for many animals, and invariably alter selection on traits adapted to previous environments. Those species that survive often have modified their habitat or their phenotype through plasticity or genetic evolution. Based on the most recent advances in this research area, we predict that individuals with highly plastic capacities, those that are generally shy, with high cognitive abilities and stress responses – in other words, individuals displaying a reactive phenotype – would better perform in human-modified landscapes than their counterparts’ proactive phenotypes. Moreover, we hypothesize that when human presence reduces predation, this decouples commonly associated traits resulting in a new range of phenotypes, with individuals characterized by low aggressiveness and physiological stress responses but high boldness, cognitive abilities and plasticity. We coin these individuals as “preactive”, being part proactive and part reactive. While supported by some studies, demonstrating the existence of this new coping style will require additional multivariate studies investigating behavioral and physiological responses to multiple challenges in HIREC impacted species.

The development of alternate energy resources is of great interest to meet the growing energy demand. Herein, we demonstrate the production of bioelectricity as well as Synechocystis sp. from dairy industry wastewater using an algal assisted microbial fuel cell (AAMFC) under different initial anodic microbial loads comprising Enterobacter aerogenes and Rhodobacter sphaeroides. Synechocystis sp. and municipal solid waste leachate present in the cathode chamber served as terminal electron acceptors. Synergistic interaction of dark and photo-fermentation at the anode region was better at a ratio of 1:9, which gave power density of 114±6 mW/m2 and COD removal of 84%. This showed higher Synechocystis sp. and lipid productivity besides highest DO level of 9.2 mgL-1 in the cathode chamber. Better performance of AAMFC was observed at pH 7.5. E. aerogenes was found to grow much faster and dominant volatile fatty acid (VFA) produced was acetic acid. Carbon dioxide fixation by Synechocystis sp. exhibited biomass and lipid productivity of 156.3±1.5 and 28.8± 4.2 mg L-1 d-1, respectively with 88.6% and 89.4% total nitrogen and phosphorous removal.

Rationale, aims and objectives: The main component of error minimization in operating rooms (ORs) is to maintain high reliability of surgical teams. The analysis of adverse events in the OR reveals deficiencies in cognitive and interpersonal skills as the main factors influencing surgeons’ errors. Therefore, research of these additional factors is necessary, besides factors related to surgeons’ clinical knowledge and technical skills. In this paper, the key factors for evaluating activities in surgical operating rooms are identified. Method: Fuzzy analytic hierarchy process (FAHP) is used for the identification of key factors. Fifteen key factors are identified for evaluating activities in surgical operating rooms to improve the efficiency of surgical operations. For each group of activities (surgical ’capabilities’, operating room characteristics, and non-technical skills), five factors are identified. Results: As the most important, the following factors are obtained: communication, indoor environment standardization, and tool handle design. Conclusions: The aim of the analysis of these key factors is surgeons’ work capability enhancement, rational design of operating rooms, and advancement of operators’ cognitive and interpersonal skills.

Rationale, aims and objectives The main purpose of this paper is to measure the efficiency and ranking of medical diagnostic laboratories by applying a Network Data Envelopment Analysis. Methods In this study, each medical diagnostic laboratory is considered as a decision making unit (DMU) and a network data envelopment analysis (NDEA) model is utilized to calculate the efficiency of each medical diagnostic laboratory. Therefore, we design a series four-stage system composed of three main laboratory processes (the pre-test process, the test process and the post-test process). We also consider sustainability criteria in order to cover social, economic, and environmental problems of health care organizations. Results The results show that three of the 22 considered laboratories are efficient. Therefore, the network DEA approach can lead to performance scores and ultimately real ranking. Also, the average efficiency scores show that the decrease of the reception unit’s efficiency results in a decrease of the efficiency of each laboratory. Therefore, the laboratories can increase the number of patients. Along with the intermediate values of the reception unit and the sampling unit, the efficiency of the reception unit increases, which results in an increase for the overall efficiency of each laboratory. Conclusion The proposed model can appropriately help the administrators and managers to identify inefficient units in their laboratory and ultimately improve the laboratory performance.

Rationale, aims and objectives Creating networked business models is one of the innovative approaches that have the ability and potential for meeting market needs. The purpose of this study is to provide a decision making model for a fair profit sharing among the members of a diagnostic laboratory network while providing a distinctive value for the patients. Methods To identify the members of the network of laboratories, a suitable approach to calculate members’ efficiency scores is proposed. Then, the network members are classified into three groups based on their performance scores. The three groups help administrators identify eligible members, members who need to improve their performance in order to meet the minimum requirements, and members who do not qualify for admission to the network. Since the performance of the members should play a significant role in the fair profit sharing mechanism, the fair allocation of profits among network members is done by the use of Shapely’s value based on the efficiency scores of members. Results The results show that for such a fair mechanism, the efficiency and sample size (the number of samples (blood, urine) taken from the patients by the laboratories), as the two effective factors, have a decisive role in the share of profit of laboratory units of the network. In the Laboratory Services Network, members receive a number of samples according to their performance. As a result, the sample size received has a direct impact on the net income of each member. Conclusion In conclusion, it is evident that the use of Shapely value may help managers in the process of sharing profits among network members in a fair way, thereby improving network performance. In this way, incentive strategies may be created for the members of the network and long-term survival of the network may be achieved.

Understanding the processes that shape forest functioning, structure and diversity remains challenging, although an increasing amount of data documents forest systems across scales. Forest models have a long history in assimilating various data and ecological knowledge and can simulate forest dynamics over spatio-temporal scales unreachable by most empirical investigations. Here we describe the trajectories of development different forest modelling communities have followed to demonstrate the leverage that computer models offer for advancing the understanding of forest ecosystems. Using three widely applied but contrasting forest modelling approaches - species distribution models, individual-based models and dynamic global vegetation models - as examples, we show how scientific and technical advances have led models beyond their initial objectives and limitations. We provide an overview of recent model applications on current important ecological topics and pinpoint ten key questions that could, and should, be tackled with forest models in the next decade. This shows that forest models, due to their long history of assimilating empirical knowledge, their iterative and continuous development, and their complementarity, represent an invaluable toolkit to address a wide range of theoretical and applied ecological questions, hence fostering a deeper understanding of forest dynamics, particularly in the context of global change.

Applying an external electric field over a polarizable electrode or object within microchannels can induce an electric double layer (EDL) around channel walls and create induced-charge electrokinetics (ICEK) within channels. The primary consequence of the induced charge is the generation of micro-vortices around the polarizable electrode or object, presenting a great potential for various microfluidic applications. This review presents the advances in theoretical, numerical and experimental studies on the physics and applications of ICEK within microfluidics. In particular, the characteristics and performance of ICEK-based microfluidic components in active micromixers, micropumps, and microvalves are critically reviewed, followed by discussing the applications of ICEK in electrophoresis and particle/cell manipulation within microfluidics. Furthermore, the opportunities and challenges of ICEK-based microfluidic devices are highlighted. This work facilitates in recognizing deliverable ICEK-based microfluidic technologies with unprecedented functionality for the next generation of biomedical applications with predictable manufacturability and functionality.

Thermoanaerobacterium thermosaccharolyticum GSU5 was isolated from animal dung collected in a pasture plain in Buenos Aires, Argentina. This thermophilic and anaerobic microorganism was able to produce butanol and ethanol, but not acetone, using sugars such as xylose, arabinose, glucose, galactose, fructose, sucrose and cellobiose. Key metabolic enzymes leading to solvent production were identified in its genome. A detailed analysis of the solvent and organic acid biosynthetic pathway genes of sequenced strains revealed new insights into the unique metabolic features of this species. The large range of fermentable substrates and the ability to produce both ethanol and butanol without acetone makes this species an interesting candidate for second generation biofuel production.

Although they fulfill various needs of human beings, reservoirs also cause hydrological regime variation in the downstream regions, thus affecting ecological diversity. Therefore, studying the reservoir-induced hydrological alterations and ecological effects is of great significance, as it could guide the regulation of the reservoir to protect the river ecology. In this study, taking the Taizi River as an example, the impact of a reservoir on hydrological alteration and ecological diversity was comprehensively evaluated through eco-flow indicators based on the flow duration curve and multiple hydrological indicators. The results reveal that (1) the ecological indicators can be used to analyze the annual and seasonal changes in the streamflow after the construction of the reservoir. The high-flow values and frequency decrease after the construction of the reservoir, especially in the autumn, the low-flow component values increase significantly, especially in spring and summer; (2) the main influencing factors of the ecological indicators can be reflected by the relationship with precipitation, as the annual ecosurplus is not significantly affected by the reservoir, while the ecodeficit is greatly affected, and the seasonal ecological indicators (especially in spring and summer) are greatly affected by the reservoir; (3) the indicators of hydrologic alteration (IHA) show significant changes after the construction of the reservoir, and are consistent with the changes in the eco-flow indicators; the change in the Shannon Index indicates that the ecological diversity reduced after construction of the reservoir. It is controlled by the reservoir, and a new equilibrium state appears; and (4) the eco-flow indicators have a good correlation with the 32 IHAs; they can reflect the change information of most IHAs, and can avoid statistical redundancy.

Environmental variation is a constant. Difficult to predict but important ‘Black Swan’ events are increasing in frequency and magnitude, but we are only beginning to understand the ecological and evolutionary consequences of such events. Extreme events can increase or decrease eco-evolutionary heterogeneity depending on the spatial grain at which they occur. Here I present a 6-year study of 3000+ individual univoltine gall makers and their enemies from 15 populations. An extreme event in one generation homogenized a key environmental determinant of enemy attack rates and survival, but exposed gall makers to an alternative environmental driver of ecological interactions. Counterintuitively, rather than acting as an ecological or evolutionary filter, extreme events can create greater spatial variation in demography, species interactions, natural selection, and evolutionary change. I suggest that the eco-evolutionary consequences of Black Swan events can only be understood by considering the evolutionary outcome of what are often complex species interactions.

This paper presents an evaluation of the user experience (UX) design of a scholarly article page, emphasizing the interface’s usability, accessibility, and content presentation. Focusing on the structure and features of a typical academic article interface, the analysis discusses how effectively the design aids in reading, navigation, and interaction with supplementary materials. We assess core design elements, including layout, navigation, readability, and accessibility, based on usability principles and real-world user behavior in academic settings.

Building on a previous work, pseudopotential sets are developed and tested for a variety of \(sp^2\) and \(sp^3\) carbon fragments. These fragments contain only one or two explicit protons and electrons, and make use of non-atom-centred potentials. They are tested with Density Functional Theory calculations in a selection of chemical environments in which several physical characteristics, including orbital and first ionisation energies, are found to be well-reproduced. They are then employed in the reproduction of molecular absorption spectra for large organic molecules and carbon allotropes, and are found to recreate both absorption and ECD spectra to a high accuracy. They are also found significantly to increase the computational efficiency of TDDFT calculations in which they are used.

The sandstone of Niche of Sakyamuni Entering Nirvana statues at Dazu Rock Carvings in China has been experiencing surface weathering for an extensive period of time. To understand the weathering effects of the local environment, three experiments were set up, including dry-wet cycle, freeze-thaw cycle and acid rain cycle. In this study, the mass, surface hardness, P-wave velocity, surface microstructure, were applied to explore the sandstone weathering degree over multiple cycles (for a total of 50 periods, 350 days). Various devices (e.g., X-ray diffraction (XRD), scanning electron microscope (SEM)) were adopted to analyze the sandstone weathering mechanism. The experimental results indicate that the main sandstone deterioration is granular disintegration. For all experiments, the variation in mass decayed exponentially with the periods; while the variation in surface hardness and P-wave velocity decayed as a power function with the periods. The rankings of influencing environmental factors of sandstone weathering follow this order: acid rain cycle, freeze-thaw cycle, and dry-wet cycle. More generally, the water-rock interaction (WRI) occurs from the surface to the inner structure of the sandstone. Granular disintegration is driven by (1) the dissolution of calcite, alteration of feldspar, and water swelling and drying shrinkage of smectite; and (2) the widening inter-granular micro-cracks. The findings could provide useful insights for the protection of the studied statues.

Rationale, aims and objectives: Colour-coded wristbands (CCWs) are widely used to signal special patient status to health care professionals. However, little is known about the feasibility of CCWs. The current study describes a process evaluation of an intervention in which CCWs were used to signal special patient status to health care professionals on the neurology Ward of a university hospital in the Netherlands. In this intervention, CCWs were issued to patients with an increased risk of falling and patients with dysphagia. Methods: Quantitative and qualitative methods were used to evaluate the reach of the intervention, performance according to protocol, compliance to the intervention, staff’s opinion on the intervention, and contextual factors that may have affected the implementation of the intervention. Data were gathered by means a self-administered questionnaire among the care professionals on the neurology ward and by means of a semi-structured interview among a subgroup of care professionals who guided the implementation process on the ward. Results: Five care professionals were interviewed and 23 care professionals (57.5%) responded to the questionnaire. Most professionals indicated they had received information about the CCWs and their role in conducting the intervention. The intervention was largely performed according to protocol, however some deviations from protocol were reported with respect to how family members were informed of the intervention, how the CCWs were issued, and how often patients were inspected for having the appropriate CCWs. Overall, staff members evaluated the intervention positively and perceived patients to be content with the CCWs. Conclusion: We conclude that the CCWs were largely implemented according to protocol. Our findings highlight some challenges that can arise when implementing CCWs. Recommendations are made to optimize the feasibility of the intervention.

Lake level is a sensitive integral indicator of climate change on global and regional scales, especially in enclosed endorheic basins. Eurasia contains the largest endorheic zone with several large terminal lakes whose water levels recently underwent remarkable variations. To address the common patterns of these variations and their links to global climate change, we investigated interdecadal variabilities in lake levels in 15 selected large lakes located at three neighboring Eurasian endorheic regions— Central Asia, the Tibetan Plateau, and the Mongolian Plateau. Satellite altimetry data revealed a heterogeneous pattern of lake levels among the three regions during the period of 1992-2018: the lake levels increased significantly in Central Asia and the Tibetan Plateau but decreased in the Mongolian Plateau. The water levels of Central Asian and Tibetan lakes revealed a shift in their trends during the observation period: the increasing trend was more evident since 1997 in Central Asia, since 2005 in the northern part of the Tibetan Plateau and since 1998 in the southern part of the Tibetan Plateau. To further quantify the climatic factors contributing to these patterns, precipitation and air temperature records were analyzed by merging three global gridded climate datasets and then applying cumulative analysis and change point tests. The precipitation over the lake basins was considered the main contributor to the heterogeneous pattern of lake levels in the three regions. The shift in air temperature in around 1997 and the shifts in precipitation in around 1998 and 2005, mainly contributed to the turning point of the trend of lake levels in those regions. Our findings reveal the linkage of the heterogeneous pattern of lake water levels to climatic factors in adjacent endorheic basins, providing a further understanding of the hydrological regime in the largest endorheic zone and its sensitivity to climate change.

Human pressure on the water resources provided by natural wetlands has intensified in Brazil due to an increase in agricultural land equipped with irrigation. However, the amount of water stored in these areas, and its contribution to aquifer recharge is unknown. The objectives of this study were to determine the amount of water that can be retained in a natural wetland surrounded by farmland and to propose a model of groundwater recharge. We used remote sensing techniques involving Unmanned Aerial Vehicle (UAV) to map the area and highlight the wetland internal morphology, using RGB orthomosaic and its respective digital surface model. According to the topography of the study area, three compartments were defined. Compartment 1, corresponding to the external border of the wetland, can store 313,121.00 m³ of water; compartment 2 and 3 can store 85,923.20 m³ and 17,952.10 m³, respectively. The 2D inversion and a pseudo-3D model produced from Electrical Resistivity Tomography (ETR) data were used to visualize the subsurface geologic structure and hydrologic flow paths. Our results showed the direct interactions between groundwater (GW) and surface water (SW) in the center of the wetland (compartment 3), which constitutes the aquifer recharge zone with vertical infiltration. As the depth increases, infiltration and water flow deviate laterally in the southwest and northeast direction. The wetland is characterized as an unconfined aquifer that plays an important role in the hydrogeological dynamics of the catchment. Remotely sensed very high-resolution images allied with geophysical techniques allowed complete surface and subsurface imaging and offered visual tools that contributed to understanding the hydrodynamics of the wetland.

Predicting how warming-induced shifts in plant species-specific phenology affect species dominance remains challenging. Here, we investigated the effects of experimental warming on plant species-specific phenology and dominance as well as their relations in an alpine meadow on the Tibetan Plateau. Warming significantly advanced phenological firsts (leaf out and first flower dates) for most species, while having variable effects on phenological lasts (leaf senescence and last flower) and full phenological periods (growing season and flower duration). Experimental warming reduced community evenness and differentially impacted the species-specific dominance. Specifically, warming-induced shifts in phenological lasts and full phenological periods, rather than the single phenological firsts, are associated with changes in species dominance. Species with lengthened full phenological periods under warming increased their dominance. Our results advance our understanding of how altered species-specific phenophases can be related to changes in community structure in response to climate change.

Underpinnings of the distribution of allopolyploid species (hybrids with duplicated genome) along spatial and ecological gradients are elusive. As allopolyploid speciation combines the range of genetic and ecological characteristics of divergent diploids, allopolyploids initially show their additivity and are predicted to evolve differentiated ecological niches to establish in face of their competition. Here, we use four diploid wild wheats that differentially combined into four independent allopolyploid species to test for such additivity and assess the impact of ecological constraints on species ranges. Divergent genetic variation from diploids being fixed in heterozygote allopolyploids supports their genetic additivity. Spatial integration of comparative phylogeography and modeling of climatic niches supports ecological additivity of locally adapted diploid progenitors into allopolyploid species which subsequently colonized wide ranges. Allopolyploids fill suitable range to a larger extent than diploids and conservative evolution following the combination of divergent species appears to support their expansion under environmental changes.

Ecological processes in food webs depend on species interactions. By identifying broad-scaled interaction patterns, important information on species ecological roles may be revealed. Here, we use the group model to examine how spatial resolution and proximity influence the group structure. We examine a dataset from the Barents Sea, with species occurrences for both the whole region and 25 subregions. Specifically, we test how the group structure in the networks differ comparing i) the regional metaweb to subregions and ii) subregion to subregion. We find that more than half the species in the metaweb change groups when compared to subregions. Between subregions, networks with similar group structure are usually spatially related. Interestingly, although species overlap is important for similarity in group structure, there are notable exceptions. Our results highlight that species ecological roles differ depending on fine-scaled differences in patterns of interactions, and that local network characteristics are important to consider.