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In vitro 3D culture is an important model for tissues in vivo. Cells in different locations of 3D tissues are physiologically different, because they are exposed to different concentrations of oxygen, nutrients, and signaling molecules, and to other environmental factors (temperature, mechanical stress, etc). The majority of high-throughput assays based on 3D cultures, however, can only detect the average behavior of cells in the whole 3D construct. Isolation of cells from specific regions of 3D cultures is possible, but relies on low-throughput techniques such as tissue sectioning and micromanipulation. Based on a procedure reported previously (‘‘cells-in-gels-in-paper’’ or CiGiP), this paper describes a simple method for culture of arrays of thin planar sections of tissues, either alone or stacked to create more complex 3D tissue structures. This procedure starts with sheets of paper patterned with hydrophobic regions that form 96 hydrophilic zones. Serial spotting of cells suspended in extracellular matrix (ECM) gel onto the patterned paper creates an array of 200 micron-thick slabs of ECM gel (supported mechanically by cellulose fibers) containing cells. Stacking the sheets with zones aligned on top of one another assembles 96 3D multilayer constructs. De-stacking the layers of the 3D culture, by peeling apart the sheets of paper, ‘‘sections’’ all 96 cultures at once. It is, thus, simple to isolate 200-micron-thick cell-containing slabs from each 3D culture in the 96-zone array. Because the 3D cultures are assembled from multiple layers, the number of cells plated initially in each layer determines the spatial distribution of cells in the stacked 3D cultures. This capability made it possible to compare the growth of 3D tumor models of different spatial composition, and to examine the migration of cells in these structures.

Here we describe an ultra-low-cost origami-based approach for large-scale manufacturing of microscopes, specifically demonstrating brightfield, darkfield, and fluorescence microscopes. Merging principles of optical design with origami enables high-volume fabrication of microscopes from 2D media. Flexure mechanisms created via folding enable a flat compact design. Structural loops in folded paper provide kinematic constraints as a means for passive self-alignment. This light, rugged instrument can survive harsh field conditions while providing a diversity of imaging capabilities, thus serving wide-ranging applications for cost-effective, portable microscopes in science and education.

In accordance with the opinion of the World Health Organization and the World Water Council the development of effective technologies for the treatment of wastewater from heavy metals for their discharge into water bodies or reuse is an urgent task nowadays. Phytoremediation biotechnologies is the most environmentally friendly and cheapest way of the treatment of wastewater, suitable for sustainable development principals. The main disadvantage of the phytoremediation is the slow speed of the process. A method for accelerating the process of phytoremediation by the combined effect of magnetic and weak electric fields is proposed. The purpose of this study is to determine the values of the parameters of the magnetic and weak electric fields that are most suitable for extracting cuprum ions from wastewater using the higher aqua plants (Lemna minor). A corresponding technological process based on the results of the study is proposed. The results have shown that the removal of copper cations from sulfate solutions effectively occurs in the initial period of time (1–5 hours) under the influence of a magnetic field with an intensity of H = 2 kA/m. Under the combined influence of an electrical current with density j = 240 μA/cm2 and a magnetic field (H = 2 kA/m) the highest rate of copper extraction by duckweed leaves is achieved. Under these conditions, the greatest growth and development of plant leaves occurs. The paper presents the results of determining of the parameters of the electrochemical release from the eluate of the spent phytomass of duckweed. It has been determined that the release of metal occurs at E = 0.32 V. An original scheme for wastewater treatment from copper with subsequent separation of copper from the spent phytomass of duckweed is proposed. In general, the presented results are a scientific justification of wastewater treatment technologies and a contribution to resolving the crisis in the field of fresh water supply. An important contribution in the circular economy is a technology recommendation proposed for recovering copper from duckweed after wastewater treatment.

Samples of bleached kraft pine cellulosic pulp, either treated with an enzyme preparation (a Thermomyces lanuginosus xylanase, an Aspergillus sp. cellulase, and a multienzyme preparation NS-22086 containing both these activities) or untreated, were refined in a laboratory PFI mill. The treatment with cellulases contained in the last two preparations significantly improved the pulp’s susceptibility to refining (the target freeness value of 30°SR was achieved in a significantly shorter time), increased water retention value (WRV) and fines contents while the weighted average fiber length was significantly reduced. These changes of pulp parameters caused deterioration of paper strength properties. The treatment with the xylanase, which partially hydrolyzed xylan, small amounts of which are associated with cellulose fibers, only slightly loosened the structure of fibers. These subtle changes positively affected the susceptibility of the pulp to refining (refining energy was significantly reduced) and improved the static strength properties of paper. Thus, the treatment of kraft pulps with xylanases may lead to substantial savings of refining energy without negative effects on paper characteristics.

Since the innovation of our new half-piece elastometric respirator, this type of filtering facepiece respirator (FFR) has been used widely in Thailand. Decontamination methods including ultraviolet C (UVC) germicidal irradiation and 70% alcohol have been implemented to decontaminate these respirators. We then examined the inactivation potential of different decontamination processes on porcine epidemic diarrhea virus (PEDV) and numerous bacterial strains, most of which were skin-derived. To enable rigorous integrity of the masks after repeated decontamination processes, fit tests by the Bitrex test, tensile strength and elongation at break were also evaluated. Our results showed that UVC irradiation at a dose of 3 J/cm2 can eradicate bacteria after 60 min and viruses after 10 min. No fungi were found on the mask surface before decontamination. The good fit test results, tensile strength and elongation at break were still maintained after multiple cycles of decontamination. No evidence of physical degradation was found by gross visual inspection. Alcohol (70%) is also an easy and effective way to eradicate microorganisms on respirators. As the current pandemic is expected to continue for months to years, the need to supply adequate reserves of personnel protective equipment (PPE) and develop effective PPE reprocessing methods is crucial. Our studies demonstrated that the novel silicone mask can be safely reprocessed and decontaminated for many cycles by UVC irradiation, which will help ameliorate the shortage of important protective devices in the COVID-19 pandemic era.

The response to the COVID-19 epidemic is generating severe shortages of personal protective equipment around the world. In particular, the supply of N95 respirator masks has become severely depleted, with supplies having to be rationed and health care workers having to use masks for prolonged periods in many countries. We sought to test the ability of 7 different decontamination methods: autoclave treatment, ethylene oxide gassing (ETO), low temperature hydrogen peroxide gas plasma (LT-HPGP) treatment, vaporous hydrogen peroxide (VHP) exposure, peracetic acid dry fogging (PAF), ultraviolet C irradiation (UVCI) and moist heat (MH) treatment to decontaminate a variety of different N95 masks following experimental contamination with SARS-CoV-2 or vesicular stomatitis virus as a surrogate. In addition, we sought to determine whether masks would tolerate repeated cycles of decontamination while maintaining structural and functional integrity. All methods except for UVCI were effective in total elimination of viable virus from treated masks. We found that all respirator masks tolerated at least one cycle of all treatment modalities without structural or functional deterioration as assessed by fit testing; filtration efficiency testing results were mostly similar except that a single cycle of LT-HPGP was associated with failures in 3 of 6 masks assessed. VHP, PAF, UVCI, and MH were associated with preserved mask integrity to a minimum of 10 cycles by both fit and filtration testing. A similar result was shown with ethylene oxide gassing to the maximum 3 cycles tested. Pleated, layered non-woven fabric N95 masks retained integrity in fit testing for at least 10 cycles of autoclaving but the molded N95 masks failed after 1 cycle; filtration testing however was intact to 5 cycles for all masks. The successful application of autoclaving for layered, pleated masks may be of particular use to institutions globally due to the virtually universal accessibility of autoclaves in health care settings. Given the ability to modify widely available heating cabinets on hospital wards in well-resourced settings, the application of moist heat may allow local processing of N95 masks.

Despite measures to reduce disease transmission, a risk can occur when blood glucose meters (BGMs) are used on multiple individuals or by caregivers assisting a patient. The laboratory and in-clinic performance of a BGM system before and after disinfection should be demonstrated to guarantee accurate readings and reliable control of blood glucose (BG) for patients. In this study, an effective disinfection procedure, conducting wiping 10 times to assure a one minute contact time of the disinfectant on contaminated surface, was first demonstrated using test samples of the meter housing materials, including acrylonitrile butadiene styrene (ABS), polymethyl methacrylate (PMMA), and polycarbonate (PC), in accordance with ISO 15197:2013. After bench studies comprising 10,000 disinfection cycles, the elemental compositions of the disinfected ABS, PMMA, and PC samples were almost the same as in the original samples, as indicated by electron spectroscopy for chemical analysis. Subsequently, the validated disinfection procedure was then directly applied to disinfect 5 commercial BGM systems composed of ABS, PMMA, or PC to observe the effect of the validated disinfection procedure on meter accuracy. The results of HBsAg values after treatment with HBV sera and disinfectant wipes for each material were less than the LoD of each material of 0.020 IU/mL. Before and after the multiple disinfection cycles, 900 of 900 samples (100%) were within the system accuracy requirements of ISO 15197:2013. All of the systems showed high performance before and after the series of disinfection cycles and met the ISO 15197:2013 requirements. In addition, our results demonstrated multiple cleaning and disinfection cycles that represented normal use over the lifetime of a meter of 3-5 years. Our validated cleaning and disinfection procedure can be directly applied to other registered disinfectants for cleaning commercial BGM products in the future.

Oilseed rape straw (ORS) is a kind of biorefractory waste widely existing in the rural area of China, which is highly suitable to mix with kitchen waste (KW) and duck droppings (DD) in two-phase anaerobic digestion (AD). This research introduced the importance of KW and DD addition to improve the biogas production and biodegradation of ORS. A set of comparative experiments were conducted on two-phase mono- and co-digestion with organic load of 60 g VS/L. The total methane yield (TMY) and the biodegradation of ORS of co-digestions were obviously improving, and the synergistic effect found in the two-phase co-digestions. The optimum mixing ratio of ORS, KW and DD was 50:40:10, and the corresponding TMY and VS degradation rate of ORS were 374.5 mL/g VS and 49.7%, respectively. Addition of KW and DD maintained the pH within the optimal range for the hydrolyzing-acidification, improved the phase separation and buffering capacity of AD system.

Five full-scale wastewater treatment plants (WWTPs) in China using typical biodegradation processes (SBR, oxidation ditch, A2/O) were selected to assess the removal of four popular artificial sweeteners (ASs). All four ASs (acesulfame (ACE), sucralose (SUC), cyclamate (CYC) and saccharin (SAC)) were detected, ranging from 0.43 to 27.34μg/L in the influent. Higher concentrations of ASs were measured in winter. ACE could be partly removed by 7.11–50.76% through biodegradation and especially through the denitrifying process. The A2/O process was the most efficient at biodegrading ASs. Adsorption (by granular activated carbon (GAC) and magnetic resin) and ultraviolet radiation-based advanced oxidation processes (UV/AOPs) were evaluated to remove ASs in laboratory-scale tests. The amounts of resin adsorbed were 3.33–18.51 times more than those of GAC except for SUC. The adsorption ability of resin decreased in the order of SAC > ACE > CYC > SUC in accordance with the pKa. Degradation of ASs followed pseudo-first-order kinetics in UV/H2O2 and UV/PDS. When applied to the secondary effluent, ASs could be degraded from 30.87 to 99.93% using UV/PDS in 30 minutes and UV/PDS was more efficient and economic.

This study investigated 24 tablet crushing devices for drug loss using different methods to recover the crushed tablet. 24 devices were compared: 3 with disposable cups, 6 with disposable bags, 12 without separate vessels and 3 types of mortar and pestle. One paracetamol tablet was crushed and recovered by tapping the powder out. Where appropriate, depending on crusher size and manufacturer instructions, the powder was also recovered by mixing with water or food. Paracetamol recovery (quantity that can be delivered to a patient) and leftover (quantity remaining in the device) were measured using a validated UV method and the entire experiment was replicated 3 times. Drug recovery ranged from 86.7-98.1% when the crushed tablet was tapped out of the crushers (average loss 5.8%). Significant losses were measured for 18 crushers, particularly manually operated hand-twist crushers with a serrated crushing surface, and some devices with disposable bags or cups. Rinsing the crushed powder with water once resulted in an average of 24.2% drug loss, and this was reduced to 4.2% after a second rinse. If crushing is unavoidable, maximizing medication delivery to the patient is essential. Rinsing twice resulted in similar paracetamol recovery to tapping the powder out; however only water rinses have the potential for direct consumption by the patient, minimizing drug loss across the entire crushing and transfer process.

Endocrine disrupting chemicals (EDCs) are environmental contaminants causing increasing concerns due to their toxicity, persistence and ubiquity. In the present study, degradative capabilities of Trametes versicolor, Pleurotus ostreatus and Phanerochaete chrysosporium to act on five EDCs, which represent different classes of chemicals (phenols, parabens and phthalate) and were first applied as single compounds, were assessed. T. versicolor was selected due to its efficiency against target EDCs and its potentialities were exploited against a mixture of EDCs in a cost-effective bioremediation process. A fed-batch approach as well as a starvation strategy were applied in order to reduce the need for input of 'fresh' biomass, and avoid the requirement for external nutrients. The fungus was successfully operated in two different bioreactors over one week. Semi-batch cultures were carried out by daily adding a mixture of EDCs to the bioreactors in a total of five consecutive degradation cycles. T. versicolor was able to efficiently remove all compounds during each cycle converting up to 21 mg L-1 day-1 of the tested EDCs. The maintained ability of T. versicolor to remove EDCs without any additional nutrients represents the main outcome of this study, which enables to forecast its application in a water treatment process.

Fe-treated biochar and raw biochar produced from macroalgae are effective biosorbents of metalloids and metals, respectively. However, the treatment of complex effluents that contain both metalloid and metal contaminants presents a challenging scenario. We test a multiple-biosorbent approach to bioremediation using Fe-biochar and biochar to remediate both metalloids and metals from the effluent from a coal-fired power station. First, a model was derived from published data for this effluent to predict the biosorption of 21 elements by Fe-biochar and biochar. The modelled outputs were then used to design biosorption experiments using Fe-biochar and biochar, both simultaneously and in sequence, to treat effluent containing multiple contaminants in excess of water quality criteria. The waste water was produced during ash disposal at an Australian coal-fired power station. The application of Fe-biochar and biochar, either simultaneously or sequentially, resulted in a more comprehensive remediation of metalloids and metals compared to either biosorbent used individually. The most effective treatment was the sequential use of Fe-biochar to remove metalloids from the waste water, followed by biochar to remove metals. Al, Cd, Cr, Cu, Mn, Ni, Pb, Zn were reduced to the lowest concentration following the sequential application of the two biosorbents, and their final concentrations were predicted by the model. Overall, 17 of the 21 elements measured were remediated to, or below, the concentrations that were predicted by the model. Both metalloids and metals can be remediated from complex effluent using biosorbents with different characteristics but derived from a single feedstock. Furthermore, the extent of remediation can be predicted for similar effluents using additive models.

The total solids content of feedstocks affects the performances of anaerobic digestion and the change of total solids content will lead the change of microbial morphology in systems. In order to increase the efficiency of anaerobic digestion, it is necessary to understand the role of the total solids content on the behavior of the microbial communities involved in anaerobic digestion of organic matter from wet to dry technology. The performances of mesophilic anaerobic digestion of food waste with different total solids contents from 5% to 20% were compared and the microbial communities in reactors were investigated using 454 pyrosequencing technology. Three stable anaerobic digestion processes were achieved for food waste biodegradation and methane generation. Better performances mainly including volatile solids reduction and methane yield were obtained in the reactors with higher total solids content. Pyrosequencing results revealed significant shifts in bacterial community with increasing total solids contents. The proportion of phylum Chloroflexi decreased obviously with increasing total solids contents while other functional bacteria showed increasing trend. Methanosarcina absolutely dominated in archaeal communities in three reactors and the relative abundance of this group showed increasing trend with increasing total solids contents. These results revealed the effects of the total solids content on the performance parameters and the behavior of the microbial communities involved in the anaerobic digestion of food waste from wet to dry technologies.

Extracellular polymeric substances (EPS) play important roles in regulating the dewaterability of sludge. This study sought to elucidate the influence of EPS on the dewaterability of sludge during bioleaching process. Results showed that, in bioleaching system with the co-inoculation of Acidithiobacillus thiooxidans TS6 and Acidithiobacillus ferrooxidans LX5 (A. t+A. f system), the capillary suction time (CST) of sludge reduced from 255.9 s to 25.45 s within 48 h, which was obviously better than the controls. The correlation analysis between sludge CST and sludge EPS revealed that the sludge EPS significantly impacted the dewaterability of sludge. Sludge CST had correlation with protein content in slime and both protein and polysaccharide contents in TB-EPS and Slime+LB+TB layers, and the decrease of protein content in slime and decreases of both protein and polysaccharide contents in TB-EPS and Slime+LB+TB layers improved sludge dewaterability during sludge bioleaching process. Moreover, the low sludge pH (2.92) and the increasing distribution of Fe in the solid phase were another two factors responsible for the improvement of sludge dewaterability during bioleaching. This study suggested that during sludge bioleaching the growth of Acidithiobacillus species resulted in the decrease of sludge pH, the increasing distribution of Fe in the solid phase, and the decrease of EPS content (mainly including protein and/or polysaccharide) in the slime, TB-EPS, and Slime+LB+TB layers, all of which are helpful for sludge dewaterability enhancement.

The feedstocks for biodiesel production are predominantly from edible oils and the high cost of the feedstocks prevents its large scale application. In this study, we evaluated the oil extracted from Boettcherisca peregrine larvae (BPL) grown on solid organic wastes for biodiesel production. The oil contents detected in the BPL converted from swine manure, fermentation residue and the degreased food waste, were 21.7%, 19.5% and 31.1%, respectively. The acid value of the oil is 19.02 mg KOH/g requiring a two-step transesterification process. The optimized process of 12∶1 methanol/oil (mol/mol) with 1.5% H(2)SO(4) reacted at 70°C for 120 min resulted in a 90.8% conversion rate of free fatty acid (FFA) by esterification, and a 92.3% conversion rate of triglycerides into esters by alkaline transesterification. Properties of the BPL oil-based biodiesel are within the specifications of ASTM D6751, suggesting that the solid organic waste-grown BPL could be a feasible non-food feedstock for biodiesel production.

The challenges which the large scale microalgal industry is facing are associated with the high cost of key operations such as harvesting, nutrient supply and oil extraction. The high-energy input for harvesting makes current commercial microalgal biodiesel production economically unfeasible and can account for up to 50% of the total cost of biofuel production. Co-cultivation of fungal and microalgal cells is getting increasing attention because of high efficiency of bio-flocculation of microalgal cells with no requirement for added chemicals and low energy inputs. Moreover, some fungal and microalgal strains are well known for their exceptional ability to purify wastewater, generating biomass that represents a renewable and sustainable feedstock for biofuel production. We have screened the flocculation efficiency of the filamentous fungus A. fumigatus against 11 microalgae representing freshwater, marine, small (5 µm), large (over 300 µm), heterotrophic, photoautotrophic, motile and non-motile strains. Some of the strains are commercially used for biofuel production. Lipid production and composition were analysed in fungal-algal pellets grown on media containing alternative carbon, nitrogen and phosphorus sources contained in wheat straw and swine wastewater, respectively. Co-cultivation of algae and A. fumigatus cells showed additive and synergistic effects on biomass production, lipid yield and wastewater bioremediation efficiency. Analysis of fungal-algal pellet's fatty acids composition suggested that it can be tailored and optimised through co-cultivating different algae and fungi without the need for genetic modification.

Gradual depletion of the world petroleum reserves and the impact of environmental pollution highlight the importance of developing alternative energy resources such as plant biomass. To address these issues, intensive research has focused on the plant Jatropha curcas, which serves as a rich source of biodiesel because of its high seed oil content. However, producing biodiesel from Jatropha generates large amounts of biomass waste that are difficult to use. Therefore, the objective of our research was to analyze the effects of different conditions of torrefaction on Jatropha biomass. Six different types of Jatropha tissues (seed coat, kernel, stem, xylem, bark, and leaf) were torrefied at four different temperature conditions (200°C, 250°C, 300°C, and 350°C), and changes in the metabolite composition of the torrefied products were determined by Fourier transform-infrared spectroscopy and nuclear magnetic resonance analyses. Cellulose was gradually converted to oligosaccharides in the temperature range of 200°C-300°C and completely degraded at 350°C. Hemicellulose residues showed different degradation patterns depending on the tissue, whereas glucuronoxylan efficiently decomposed between 300°C and 350°C. Heat-induced depolymerization of starch to maltodextrin started between 200°C and 250°C, and oligomer sugar structure degradation occurred at higher temperatures. Lignin degraded at each temperature, e.g., syringyl (S) degraded at lower temperatures than guaiacyl (G). Finally, the toxic compound phorbol ester degraded gradually starting at 235°C and efficiently just below 300°C. These results suggest that torrefaction is a feasible treatment for further processing of residual biomass to biorefinery stock or fertilizer.

Choice tests are a standard method to determine preferences in bio-assays, e.g. for food types and food additives such as bait attractants and toxicants. Choice between food additives can be determined only when the food substrate is sufficiently homogeneous. This is difficult to achieve for wood eating organisms as wood is a highly variable biological material, even within a tree species due to the age of the tree (e.g. sapwood vs. heartwood), and components therein (sugar, starch, cellulose and lignin). The current practice to minimise variation is to use wood from the same tree, yet the variation can still be large and the quantity of wood from one tree may be insufficient. We used wood samples of identical volume from multiple sources, measured three physical properties (dry weight, moisture absorption and reflected light intensity), then ranked and clustered the samples using fuzzy c-means clustering. A reverse analysis of the clustered samples found a high correlation between their physical properties and their source of origin. This suggested approach allows a quantifiable, consistent, repeatable, simple and quick method to maximize control over similarity of wood used in choice tests. © 2014 Oberst et al.

It is generally accepted as a fact in the biogas technology that protein-rich biomass substrates should be avoided due to inevitable process inhibition. Substrate compositions with a low C/N ratio are considered difficult to handle and may lead to process failure, though protein-rich industrial waste products have outstanding biogas generation potential. This common belief has been challenged by using protein-rich substrates, i.e. casein and precipitated pig blood protein in laboratory scale continuously stirred mesophilic fed-batch biogas fermenters. Both substrates proved suitable for sustained biogas production (0.447 L CH4/g protein oDM, i.e. organic total solids) in high yield without any additives, following a period of adaptation of the microbial community. The apparent key limiting factors in the anaerobic degradation of these proteinaceous materials were the accumulation of ammonia and hydrogen sulfide. Changes in time in the composition of the microbiological community were determined by next-generation sequencing-based metagenomic analyses. Characteristic rearrangements of the biogas-producing community upon protein feeding and specific differences due to the individual protein substrates were recognized. The results clearly demonstrate that sustained biogas production is readily achievable, provided the system is well-characterized, understood and controlled. Biogas yields (0.45 L CH4/g oDM) significantly exceeding those of the commonly used agricultural substrates (0.25-0.28 L CH4/g oDM) were routinely obtained. The results amply reveal that these high-energy-content waste products can be converted to biogas, a renewable energy carrier with flexible uses that can replace fossil natural gas in its applications. Process control, with appropriate acclimation of the microbial community to the unusual substrate, is necessary. Metagenomic analysis of the microbial community by next-generation sequencing allows a precise determination of the alterations in the community composition in the course of the process.

This paper uses event study based on the Generalized Autoregressive Conditional Heteroscedasticity (GARCH) model to study the impact of the COVID-19 outbreak on China’s financial market. It finds that the pandemic had an overall significant and negative impact on the stock prices of firms listed on SSE, SZSE and ChiNext. However, such impact appeared to be heterogeneous across industries, affecting listed firms in industries such as pharmaceutical and telecommunications positively, but those in services industries such as accommodation, catering, and commercial services negatively. Apparently, a crisis for some had been an opportunity for others. In addition, this paper seeks to understand the micro mechanism behind the heterogeneity of pandemic shock from the perspective of firms’ financial position. It finds that listed firms with higher debt level were hit harder, whereas those with more net cash flow had displayed higher resilience against the blow of the pandemic. However, the opposite pattern is found among those listed on ChiNext and in industries severely devastated by the pandemic. These findings have policy implications in terms of preventing systemic financial risks and facilitating recovery during pandemic-induced economic downturns. It also helps investor adjust investment strategies, hedge against risks, and secure gains when the market conditions in general are unfavorable.

Cannabis sativais relatively recalcitrant tode novoregeneration, but several studies have reported shoot organogenesis or somatic embryogenesis from non-meristematic tissues. Most report infrequent regeneration rates from these tissues, but a landmark publication from 2010 achieved regeneration from leaf explants with a 96% response rate, producing an average of 12.3 shoots per explant in a single drug-type accession. Despite the importance regeneration plays in plant biotechnology and the renewed interest in this crop the aforementioned protocol has not been used in subsequent papers in the decade since it was published, raising concerns over its reproducibility. Here we attempted to replicate this importantCannabisregeneration study and expand the original scope of the study by testing it across 10 drug-typeC.sativagenotypes to assess genotypic variation. In our study, callus was induced in all 10 genotypes but callus growth and appearance substantially differed among cultivars, with the most responsive genotype producing 6-fold more callus than the least responsive. The shoot induction medium failed to induce shoot organogenesis in any of the 10 cultivars tested, instead resulting in necrosis of the calli. The findings of this replication study raise concerns about the replicability of existing methods. However, some details of the protocol could not be replicated due to missing details in the original paper and regulatory issues, which could have impacted the outcome. These results highlight the importance of using multiple genotypes in such studies and providing detailed methods to facilitate replication.

Background Forensic odontology (FO) is regarded in the literature as one of the most reliable and economical scientific methods for victim identification in mass disasters (MDs). The present paper systematically reviews the role of forensic odontologists in various global MDs. Method A comprehensive search of the literature databases (PubMed, Medline, SCOPUS, Web of Science and Google Scholar), along with cross-referencing published peer-reviewed articles, was conducted. The search included full texts, abstracts or titles, had no inclusion year limit (searched until September 2017) and was limited to the English language. Keywords included a combination of ‘Forensic odontology’, ‘Dental records’, ‘Victim identification’, ‘Natural mass disaster’, ‘Criminal mass disaster’, ‘Accidental mass disaster’ and ‘Victim disaster’. Results Of the included disasters (20), 12 (57.14%) were accidental, 5 (23.80%) natural and 3 (19.04%) were criminal. The maximum number of victims was associated with the Japan tsunami (15892), followed by the Thailand tsunami (4280) and the Estonia ferry disaster (852). A total of 23654 victims were reported, of which 20569 (86.96%) were positively identified. Reports from 17 MDs included the use of FO in victim identification [3025 (14.70%) cases]. In addition, 1094 victims (5.31%; from 7 papers) were identified using FO in combination with other methodologies. The highest percentage of victims was identified using FO following the Kentucky air crash (47; 100%), followed by the Newark air crash (38; 76%), the Nepal air crash (10; 71.42%), the France air crash (56; 65.88%), the Australian bushfire (14; 63.63%), and the Estonia ferry disaster (57; 60.63%). Conclusion FO has played a significant role in victim identification in several MDs around the world. The success of FO-based identification is heavily dependent on the availability of ante-mortem records from general dental practitioners. Hence, adequate knowledge about FO and appropriate dental record keeping among general dental practitioners are critical.

This paper assesses the extent to which patent renewal data is associated with government funding in a university context by focusing on the relationship between the funded patentees and renewal decisions of their patents. The aim of this paper is to show whether receiving funding from government contributes to high-value patents as measured by the patent renewal decisions made by their owners. Our observations of academic nanotechnology patents in Canada discovered a positive relationship between funded researchers and the rate of patent renewal after 4 years. Further analysis is also undertaken into the relative impact on patent renewal after 8 years and 12 years. Our results suggest that the length of patent renewal in numbers of years can be related to levels of government funding received by their inventors.

One of the main strategies to control the spread of infectious animal diseases is the implementation of movement restrictions. This paper shows a loss in efficiency of the movement restriction policy (MRP) when behavioral responses of farmers are taken into account. Incorporating the strategic behavior of farmers in an epidemiologic model reveals that the MRP can trigger premature animal sales by farms at high risk of becoming infected that significantly reduce the efficacy of the policy. The results are validated in a parameterized network via Monte Carlo simulations and measures to mitigate the loss of efficiency of the MRP are discussed. Financial aid to farmers can be justified by public health concerns, not only for equity. This paper contributes to developing an interdisciplinary analytical framework regarding the expansion of infectious diseases combining economic and epidemiologic dimensions.

International audience; Vagus nerve stimulation (VNS) is an established adjunctive therapy for pharmacologically refractory epilepsy and depression and is currently in active clinical research for other applications. In current clinical studies, VNS is delivered in an open-loop approach, where VNS parameters are defined during a manual titration phase. However, the physiological response to a given VNS configuration shows significant inter and intra-patient variability and may significantly evolve through time. VNS closed-loop approaches, allowing for the optimization of the therapy in an adaptive manner, may be necessary to improve efficacy while reducing side effects. This paper proposes a generic, closed-loop control VNS system that is able to optimize a number of VNS parameters in an adaptive fashion, in order to keep a control variable within a specified range. Although the proposed control method is completely generic, an example application using the cardiac beat to beat interval (RR) as control variable will be developed in this paper. The proposed controller is based on a state transition model (STM) that can be configured using a partially or a fully-connected architecture, different model orders and different state-transition algorithms. The controller is applied to the adaptive regulation of heart rate and evaluated on 6 sheep, for 13 different targets, using partially-connected STM with 10 states. Also, partially and fully-connected STM defined by 30 states were applied to 7 other sheep for the same 10 targets. Results illustrate the interest of the proposed fully-connected STM and the feasibility of integrating this control system into an implantable neuromodulator.

International audience; The predominant clonal evolution (PCE) model seeks to formulate a common population genetics framework for all micropathogens (namely, parasitic protozoa, fungi and yeasts, bacteria, and viruses). It relies on a definition of clonality that is only based on population structure features (namely, strongly restrained genetic recombination). Its clear-cut properties make it of strong interest for applied and basic research, since it permits the definition of stable, clearly delimited units of analysis below the species level: clonal genotypes and discrete genetic subdivisions ("near-clades"). These units of analysis can be used for clinical and epidemiological studies, vaccine and drug design, species description, and evolutionary studies on natural and experimental populations. In this review, the evolutionary and population genetics background of the model will be only briefly mentioned, while considerable emphasis will be given to its practical significance for the study and control of neglected tropical diseases. The goal of the paper is to make this practical usefulness accessible to a broad audience of readers, including scientists who are not evolution specialists, such as epidemiologists, field scientists, and clinicians. For extensive developments about the evolutionary background of the model, see our previous papers [1-9]. Citations of these former articles lead to the many references quoted in them, which cannot be listed again here. Methods: Brief recall of the PCE model and how it has been designed The PCE model of pathogenic microorganisms explores the population structure and evolution of whole, presently described species in their complete ecogeographical range in the long term. It aims at evaluating to what extent genetic recombination is inhibited in the species PLOS Neglected Tropical Diseases | https://doi.

Background: Biosensor-based detection provides a rapid and low-cost alternative to conventional analytical methods for revealing the presence of the contaminants in water as well as solid matrices. Although important to be detected, small analytes (few hundreds of Daltons) are an issue in biosensing since the signal they induce in the transducer, and specifically in a Quartz-Crystal Microbalance, is undetectable. A pesticide like parathion (M = 292 Da) is a typical example of contaminant for which a signal amplification procedure is desirable. Methods/Findings: The ballasting of the analyte by gold nanoparticles has been already applied to heavy target as proteins or bacteria to improve the limit of detection. In this paper, we extend the application of such a method to small analytes by showing that once the working surface of a Quartz-Crystal Microbalance (QCM) has been properly functionalized, a limit of detection lower than 1 ppb is reached for parathion. The effective surface functionalization is achieved by immobilizing antibodies upright oriented on the QCM gold surface by a simple photochemical technique (Photonic Immobilization Technique, PIT) based on the UV irradiation of the antibodies, whereas a simple protocol provided by the manufacturer is applied to functionalize the gold nanoparticles. Thus, in a non-competitive approach, the small analyte is made detectable by weighing it down through a “sandwich protocol” with a second antibody tethered to heavy gold nanoparticles. The immunosensor has been proved to be effective against the parathion while showing no cross reaction when a mixture of compounds very similar to parathion is analyzed. Conclusion/Significance: The immunosensor described in this paper can be easily applied to any small molecule for which polyclonal antibodies are available since both the functionalization procedure of the QCM probe surface and gold nanoparticle can be applied to any IgG, thereby making our device of general application in terms of target analyte. Published version

Traditional descriptions of the knee suggest that the function of the patella is to facilitate knee extension by increasing the moment arm of the quadriceps muscles. Through modelling and evidence from the literature it is shown in this paper that the presence of the patella makes the ability of the quadriceps to rotate the thigh greater than their ability to rotate the tibia. Furthermore, this difference increases as the knee is flexed, thus demonstrating a pattern that is consistent with many human movements. This paper also shows that the anterior cruciate ligament plays a previously unheralded role in extending the shank and that translation at the tibiofemoral and patellofemoral joints is important in improving the capacity for thigh rotation when the knee is flexed. This study provides new insights as to how the structure of the knee is adapted to its purpose and illustrates how the functional anatomy of the knee contributes to its extension function.

Background: The alkalistable and thermostable xylanases are in high demand for pulp bleaching in paper industry and generating xylooligosaccharides by hydrolyzing xylan component of agro-residues. The compost-soil samples, one of the hot environments, are expected to be a rich source of microbes with thermostable enzymes. Methodology/Principal Findings: Metagenomic DNA from hot environmental samples could be a rich source of novel biocatalysts. While screening metagenomic library constructed from DNA extracted from the compost-soil in the p18GFP vector, a clone (TSDV-MX1) was detected that exhibited clear zone of xylan hydrolysis on RBB xylan plate. The sequencing of 6.321 kb DNA insert and its BLAST analysis detected the presence of xylanase gene that comprised 1077 bp. The deduced protein sequence (358 amino acids) displayed homology with glycosyl hydrolase (GH) family 11 xylanases. The gene was subcloned into pET28a vector and expressed in E. coli BL21 (DE3). The recombinant xylanase (rMxyl) exhibited activity over a broad range of pH and temperature with optima at pH 9.0 and 80 degrees C. The recombinant xylanase is highly thermostable having T1/2 of 2 h at 80 degrees C and 15 min at 90 degrees C. Conclusion/Significance: This is the first report on the retrieval of xylanase gene through metagenomic approach that encodes an enzyme with alkalistability and thermostability. The recombinant xylanase has a potential application in paper and pulp industry in pulp bleaching and generating xylooligosaccharides from the abundantly available agro-residues.

Maintaining bone volume during bone turnover by a BMU is known as bone balance. Balance is required to maintain structural integrity of the bone and is often dysregulated in disease. Consequently, understanding how a BMU controls bone balance is of considerable interest. This paper develops a methodology for identifying potential balance controls within a single cortical BMU. The theoretical framework developed offers the possibility of a directed search for biological processes compatible with the constraints of balance control. We first derive general control constraint equations and then introduce constitutive equations to identify potential control processes that link key variables that describe the state of the BMU. The paper describes specific local bone volume balance controls that may be associated with bone resorption and bone formation. Because bone resorption and formation both involve averaging over time, short-term fluctuations in the environment are removed, leaving the control systems to manage deviations in longer-term trends back towards their desired values. The length of time for averaging is much greater for bone formation than for bone resorption, which enables more filtering of variability in the bone formation environment. Remarkably, the duration for averaging of bone formation may also grow to control deviations in long-term trends of bone formation. Providing there is sufficient bone formation capacity by osteoblasts, this leads to an extraordinarily robust control mechanism that is independent of either osteoblast number or the cellular osteoid formation rate. A complex picture begins to emerge for the control of bone volume. Different control relationships may achieve the same objective, and the ‘integration of information’ occurring within a BMU may be interpreted as different sets of BMU control systems coming to the fore as different information is supplied to the BMU, which in turn leads to different observable BMU behaviors.

While there is a vast literature on the control systems that cells utilize to regulate their own state, there is little published work on the formal application of control theory to the external regulation of cellular functions. This paper chooses the GAL network in S. cerevisiae as a well understood benchmark example to demonstrate how control theory can be employed to regulate intracellular mRNA levels via extracellular galactose. Based on a mathematical model reduced from the GAL network, we have demonstrated that a galactose dose necessary to drive and maintain the desired GAL genes' mRNA levels can be calculated in an analytic form. And thus, a proportional feedback control can be designed to precisely regulate the level of mRNA. The benefits of the proposed feedback control are extensively investigated in terms of stability and parameter sensitivity. This paper demonstrates that feedback control can both significantly accelerate the process to precisely regulate mRNA levels and enhance the robustness of the overall cellular control system.

Computational procedures for predicting metabolic interventions leading to the overproduction of biochemicals in microbial strains are widely in use. However, these methods rely on surrogate biological objectives (e.g., maximize growth rate or minimize metabolic adjustments) and do not make use of flux measurements often available for the wild-type strain. In this work, we introduce the OptForce procedure that identifies all possible engineering interventions by classifying reactions in the metabolic model depending upon whether their flux values must increase, decrease or become equal to zero to meet a pre-specified overproduction target. We hierarchically apply this classification rule for pairs, triples, quadruples, etc. of reactions. This leads to the identification of a sufficient and non-redundant set of fluxes that must change (i.e., MUST set) to meet a pre-specified overproduction target. Starting with this set we subsequently extract a minimal set of fluxes that must actively be forced through genetic manipulations (i.e., FORCE set) to ensure that all fluxes in the network are consistent with the overproduction objective. We demonstrate our OptForce framework for succinate production in Escherichia coli using the most recent in silico E. coli model, iAF1260. The method not only recapitulates existing engineering strategies but also reveals non-intuitive ones that boost succinate production by performing coordinated changes on pathways distant from the last steps of succinate synthesis., Author Summary Over the past few years, there has been an unprecedented increase in the use of microorganisms for the production of biofuels, industrial chemicals and pharmaceutical precursors. In this regard, biotechnologists are confronted with the challenge to efficiently convert biomass and other renewable resources into useful biochemicals. With the advent of organism-specific mathematical models of metabolism, scientists have used computations to identify genetic modifications that maximize the yield of a desired product. In this paper, we introduce OptForce, an algorithm that identifies all possible metabolic interventions that lead to the overproduction of a biochemical of interest. Unlike existing techniques, OptForce does not rely on the maximization of a fitness function to predict metabolic fluxes. Instead, OptForce contrasts the metabolic flux patterns observed in an initial strain and a strain overproducing the chemical at the target yield. The essence of this procedure is the identification of all coordinated reaction modifications that force the network towards the overproduction target. We used OptForce to predict metabolic interventions for succinate overproduction in Escherichia coli. The results described in this paper not only uncover existing strain designs for succinate production but also elucidate new ones that can be experimentally explored.

This paper presents an in silico optimization method of metabolic pathway production. The metabolic pathway can be represented by a mathematical model known as the generalized mass action model, which leads to a complex nonlinear equations system. The optimization process becomes difficult when steady state and the constraints of the components in the metabolic pathway are involved. To deal with this situation, this paper presents an in silico optimization method, namely the Newton Cooperative Genetic Algorithm (NCGA). The NCGA used Newton method in dealing with the metabolic pathway, and then integrated genetic algorithm and cooperative co-evolutionary algorithm. The proposed method was experimentally applied on the benchmark metabolic pathways, and the results showed that the NCGA achieved better results compared to the existing methods.

Recent developments in dental implant have heightened the urgent need to natural tissue adhesives estrogenic materials with ability of promoting the proliferation and osteoblastic differentiation in human dental pulp-derived stem cells, to provide better integration of tissue for dentistry. Up to now, far little attention has been paid to adhesives extract of the root of Ferula sp. which contains biomaterial compounds with estrogenic activities. Prior to undertaking the investigation, analysis of the extract of the root of F. ovina revealed a novel terpenoid, and we identified it as Fenoferin. So far, this paper has focused on Fenoferin compared to Ferutinin and root extract to determine if Fenoferin caused changes in craniofacial cartilage, bone (ceratohyal) and tooth mineralization. Following the purpose of study, we used zebrafish as a well-developed model system for studying bone development, so the developing zebrafish larvae were exposed to various concentration of compounds at 2dpf, and the histological analyses were performed at 6dpf. The result of the current study highlights the importance of F. ovina in studies related to dental regenerative medicine.

Assessing and selecting the most viable embryos for transfer is an essential part of in vitro fertilization (IVF). In recent years, several approaches have been made to improve and automate the procedure using artificial intelligence (AI) and deep learning. Based on images of embryos with known implantation data (KID), AI models have been trained to automatically score embryos related to their chance of achieving a successful implantation. However, as of now, only limited research has been conducted to evaluate how embryo selection models generalize to new clinics and how they perform in subgroup analyses across various conditions. In this paper, we investigate how a deep learning-based embryo selection model using only time-lapse image sequences performs across different patient ages and clinical conditions, and how it correlates with traditional morphokinetic parameters. The model was trained and evaluated based on a large dataset from 18 IVF centers consisting of 115,832 embryos, of which 14,644 embryos were transferred KID embryos. In an independent test set, the AI model sorted KID embryos with an area under the curve (AUC) of a receiver operating characteristic curve of 0.67 and all embryos with an AUC of 0.95. A clinic hold-out test showed that the model generalized to new clinics with an AUC range of 0.60–0.75 for KID embryos. Across different subgroups of age, insemination method, incubation time, and transfer protocol, the AUC ranged between 0.63 and 0.69. Furthermore, model predictions correlated positively with blastocyst grading and negatively with direct cleavages. The fully automated iDAScore v1.0 model was shown to perform at least as good as a state-of-the-art manual embryo selection model. Moreover, full automatization of embryo scoring implies fewer manual evaluations and eliminates biases due to inter- and intraobserver variation.

The variability of the heart rate (HRV) is widely studied as it contains information about the activity of the autonomic nervous system (ANS). However, HRV is influenced by breathing, independently of ANS activity. It is therefore important to include respiratory information in HRV analyses in order to correctly interpret the results. In this paper, we propose to record respiratory activity and use this information to separate the tachogram in two components: one which is related to breathing and one which contains all heart rate variations that are unrelated to respiration. Several algorithms to achieve this have been suggested in the literature, but no comparison between the methods has been performed yet. In this paper, we conduct two studies to evaluate the methods' performances to accurately decompose the tachogram in two components and to assess the robustness of the algorithms. The results show that orthogonal subspace projection and an ARMAX model yield the best performances over the two comparison studies. In addition, a real-life example of stress classification is presented to demonstrate that this approach to separate respiratory information in HRV studies can reveal changes in the heart rate variations that are otherwise masked by differing respiratory patterns. ispartof: PLoS One vol:9 issue:7 ispartof: location:United States status: published

Background The Wolbachia strategy aims to manipulate mosquito populations to make them incapable of transmitting dengue viruses between people. To test its efficacy, this strategy requires field trials. Public consultation and engagement are recognized as critical to the future success of these programs, but questions remain regarding how to proceed. This paper reports on a case study where social research was used to design a community engagement framework for a new dengue control method, at a potential release site in central Vietnam. Methodology/Principal Findings The approach described here, draws on an anthropological methodology and uses both qualitative and quantitative methods to design an engagement framework tailored to the concerns, expectations, and socio-political setting of a potential trial release site for Wolbachia-infected Aedes aegypti mosquitoes. The process, research activities, key findings and how these were responded to are described. Safety of the method to humans and the environment was the most common and significant concern, followed by efficacy and impact on local lives. Residents expected to be fully informed and engaged about the science, the project, its safety, the release and who would be responsible should something go wrong. They desired a level of engagement that included regular updates and authorization from government and at least one member of every household at the release site. Conclusions/Significance Results demonstrate that social research can provide important and reliable insights into public concerns and expectations at a potential release site, as well as guidance on how these might be addressed. Findings support the argument that using research to develop more targeted, engagement frameworks can lead to more sensitive, thorough, culturally comprehensible and therefore ethical consultation processes. This approach has now been used successfully to seek public input and eventually support for releases Wolbachia-infected mosquitoes, in two different international settings - Australia and Vietnam., Author Summary In recent years, a number of new strategies using novel technologies for the control of dengue fever control have emerged. These strategies are notably different from their predecessors and not without controversy. Many also require open release field trials to test their efficacy. Public consultation and engagement are recognized as critical to the future success of these programs, but questions remain regarding how to proceed. In this paper we describe an approach to public engagement that uses social research to design an engagement framework and communication materials tailored to the concerns, expectations, and socio-political setting of potential trial release sites. This approach was developed and implemented in Australia (2008–2010) where the first publicly supported field trials occurred January 2011. We report here on the implementation of this approach in Vietnam (2009–2010) where the second release will occur in 2014. This paper describes the process, research activities, outcomes and key findings from the Vietnamese field site. It highlights key public concerns and expectations about engagement and authorization and shows how these were used to develop a more targeted, culturally appropriate and comprehensible engagement framework and communication materials. The paper demonstrates the viability of this approach to community engagement for new dengue control strategies, in a ‘developing’ country context.

This paper proposed a novel bionic selective visual attention mechanism to quickly select regions that contain salient objects to reduce calculations. Firstly, lateral inhibition filtering, inspired by the limulus' ommateum, is applied to filter low-frequency noises. After the filtering operation, we use Artificial Bee Colony (ABC) algorithm based selective visual attention mechanism to obtain the interested object to carry through the following recognition operation. In order to eliminate the camera motion influence, this paper adopted ABC algorithm, a new optimization method inspired by swarm intelligence, to calculate the motion salience map to integrate with conventional visual attention. To prove the feasibility and effectiveness of our method, several experiments were conducted. First the filtering results of lateral inhibition filter were shown to illustrate its noise reducing effect, then we applied the ABC algorithm to obtain the motion features of the image sequence. The ABC algorithm is proved to be more robust and effective through the comparison between ABC algorithm and popular Particle Swarm Optimization (PSO) algorithm. Except for the above results, we also compared the classic visual attention mechanism and our ABC algorithm based visual attention mechanism, and the experimental results of which further verified the effectiveness of our method.

Although many endo-ß-1,4-glucanases have been isolated in invertebrates, their cellulolytic systems are not fully understood. In particular, gastropod feeding on seaweed is considered an excellent model system for production of bioethanol and renewable bioenergy from third-generation feedstocks (microalgae and seaweeds). In this study, enzymes involved in the conversion of cellulose and other polysaccharides to glucose in digestive fluids of the sea hare (Aplysia kurodai) were screened and characterized to determine how the sea hare obtains glucose from sea lettuce (Ulva pertusa). Four endo-ß-1,4-glucanases (21K, 45K, 65K, and 95K cellulase) and 2 ß-glucosidases (110K and 210K) were purified to a homogeneous state, and the synergistic action of these enzymes during cellulose digestion was analyzed. All cellulases exhibited cellulase and lichenase activities and showed distinct cleavage specificities against cellooligosaccharides and filter paper. Filter paper was digested to cellobiose, cellotriose, and cellotetraose by 21K cellulase, whereas 45K and 65K enzymes hydrolyzed the filter paper to cellobiose and glucose. 210K ß-glucosidase showed unique substrate specificity against synthetic and natural substrates, and 4-methylumbelliferyl (4MU)-ß-glucoside, 4MU-ß-galactoside, cello-oligosaccharides, laminarin, and lichenan were suitable substrates. Furthermore, 210K ß-glucosidase possesses lactase activity. Although ß-glucosidase and cellulase are necessary for efficient hydrolysis of carboxymethylcellulose to glucose, laminarin is hydrolyzed to glucose only by 210K ß-glucosidase. Kinetic analysis of the inhibition of 210K ß-glucosidase by D-glucono-1,5-lactone suggested the presence of 2 active sites similar to those of mammalian lactase-phlorizin hydrolase. Saccharification of sea lettuce was considerably stimulated by the synergistic action of 45K cellulase and 210K ß-glucosidase. Our results indicate that 45K cellulase and 210K ß-glucosidase are the core components of the sea hare digestive system for efficient production of glucose from sea lettuce. These findings contribute important new insights into the development of biofuel processing biotechnologies from seaweed.

Nicotinamidases catalyze the hydrolysis of nicotinamide to nicotinic acid and ammonia, an important reaction in the NAD(+) salvage pathway. This paper reports a new nicotinamidase from the deep-sea extremely halotolerant and alkaliphilic Oceanobacillus iheyensis HTE831 (OiNIC). The enzyme was active towards nicotinamide and several analogues, including the prodrug pyrazinamide. The enzyme was more nicotinamidase (kcat/Km = 43.5 mM(-1)s(-1)) than pyrazinamidase (kcat/Km = 3.2 mM(-1)s(-1)). Mutational analysis was carried out on seven critical amino acids, confirming for the first time the importance of Cys133 and Phe68 residues for increasing pyrazinamidase activity 2.9- and 2.5-fold, respectively. In addition, the change in the fourth residue involved in the ion metal binding (Glu65) was detrimental to pyrazinamidase activity, decreasing it 6-fold. This residue was also involved in a new distinct structural motif DAHXXXDXXHPE described in this paper for Firmicutes nicotinamidases. Phylogenetic analysis revealed that OiNIC is the first nicotinamidase described for the order Bacillales.

As biomedical investigators strive to integrate data and analyses across spatiotemporal scales and biomedical domains, they have recognized the benefits of formalizing languages and terminologies via computational ontologies. Although ontologies for biological entities—molecules, cells, organs—are well-established, there are no principled ontologies of physical properties—energies, volumes, flow rates—of those entities. In this paper, we introduce the Ontology of Physics for Biology (OPB), a reference ontology of classical physics designed for annotating biophysical content of growing repositories of biomedical datasets and analytical models. The OPB's semantic framework, traceable to James Clerk Maxwell, encompasses modern theories of system dynamics and thermodynamics, and is implemented as a computational ontology that references available upper ontologies. In this paper we focus on the OPB classes that are designed for annotating physical properties encoded in biomedical datasets and computational models, and we discuss how the OPB framework will facilitate biomedical knowledge integration.

In this paper, we describe a server/client literature management system specialized for the life science domain, the TogoDoc system (Togo, pronounced Toe-Go, is a romanization of a Japanese word for integration). The server and the client program cooperate closely over the Internet to provide life scientists with an effective literature recommendation service and efficient literature management. The content-based and personalized literature recommendation helps researchers to isolate interesting papers from the "tsunami" of literature, in which, on average, more than one biomedical paper is added to MEDLINE every minute. Because researchers these days need to cover updates of much wider topics to generate hypotheses using massive datasets obtained from public databases or omics experiments, the importance of having an effective literature recommendation service is rising. The automatic recommendation is based on the content of personal literature libraries of electronic PDF papers. The client program automatically analyzes these files, which are sometimes deeply buried in storage disks of researchers' personal computers. Just saving PDF papers to the designated folders makes the client program automatically analyze and retrieve metadata, rename file names, synchronize the data to the server, and receive the recommendation lists of newly published papers, thus accomplishing effortless literature management. In addition, the tag suggestion and associative search functions are provided for easy classification of and access to past papers (researchers who read many papers sometimes only vaguely remember or completely forget what they read in the past). The TogoDoc system is available for both Windows and Mac OS X and is free. The TogoDoc Client software is available at http://tdc.cb.k.u-tokyo.ac.jp/, and the TogoDoc server is available at https://docman.dbcls.jp/pubmed_recom.

The R2R3-MYB transcription factor MYB46 functions as a master switch for secondary cell wall biosynthesis, ensuring the exquisite expression of the secondary wall biosynthetic genes in the tissues where secondary walls are critical for growth and development. At the same time, suppression of its function is needed when/where formation of secondary walls is not desirable. Little is known about how this opposing control of secondary cell wall formation is achieved. We used both transient and transgenic expression of MYB46 and mitogen-activated protein kinase 6 (MPK6) to investigate the molecular mechanism of the post-translational regulation of MYB46. We show that MYB46 is phosphorylated by MPK6, leading to site specific phosphorylation-dependent degradation of MYB46 by the ubiquitin-mediated proteasome pathway. In addition, the MPK6-mediated MYB46 phosphorylation was found to regulate in planta secondary wall forming function of MYB46. Furthermore, we provide experimental evidences that MYB83, a paralog of MYB46, is not regulated by MPK6. The coupling of MPK signaling to MYB46 function provides insights into the tissue- and/or condition-specific activity of MYB46 for secondary wall biosynthesis., Author summary Secondary cell walls are critical for plant growth and of economic importance to humans as fiber, pulp for paper, and as a renewable source of energy. A master switch for secondary wall biosynthesis, MYB46, ensures the exquisite expression of the biosynthetic genes in the tissues where secondary walls are critical. However, suppression of secondary wall formation is needed during impermanent cessation of vegetative growth triggered by environmental stresses. Although the expression of MYB46 is upregulated by abiotic stresses, secondary wall formation may not occur. How is this opposing control achieved? The mitogen-activated protein kinase (MPK) cascade is among the most conserved signal transduction systems in eukaryotes and plays a crucial role in the regulation of biochemical and physiological changes associated with environmental stimuli and phytohormones. In this report, we show that MYB46 is negatively regulated by MPK6 during salt stress, providing a novel insight into a mechanism by which plants incorporate environmental signals into differential regulation of secondary wall biosynthesis.

To reduce metal artifacts, several sinogram inpainting-based metal artifact reduction (MAR) methods have been proposed where projection data within the metal trace region of the sinogram are treated as missing and subsequently estimated. However, these methods generally assume data truncation does not occur and all metal objects reside inside the field-of-view (FOV). For small FOV imaging, these assumptions are violated, and thus existing inpainting-based MAR methods would not be effective. In this paper, we propose a new MAR method to reduce metal artifacts effectively in the presence of data truncation. The main idea behind the proposed method is the synthesis of a sinogram, which is treated as the originally measured sinogram. First, an initial reconstruction step is performed to remove truncation artifacts. The next step consists of a forward projection of the small FOV image, replacing the original sinogram with the synthesized sinogram. The final step is the application of sinogram inpainting based MAR methods using the synthesized sinogram. Verification of the proposed method was performed for three situations: extended cardiac-torso (XCAT) simulation, clinical data, and experimental data. The proposed method was applied with linear MAR (LMAR) and normalized MAR (NMAR), and the performance of the proposed method was compared with that of the previous method. For quantitative evaluation, normalized mean squared error (NMSE) and structure similarity (SSIM) were used. The results show the effectiveness of the proposed method to reduce residual metal artifacts, which are present in the results obtained with the previous method. The evaluation results using NMSE and SSIM also indicate that the proposed method is more effective than the previous method.

The partial success of tumor immunotherapy induced by checkpoint blockade, which is not antigen-specific, suggests that the immune system of some patients contain antigen receptors able to specifically identify tumor cells. Here we focused on T-cell receptor (TCR) repertoires associated with spontaneous breast cancer. We studied the alpha and beta chain CDR3 domains of TCR repertoires of CD4 T cells using deep sequencing of cell populations in mice and applied the results to published TCR sequence data obtained from human patients. We screened peripheral blood T cells obtained monthly from individual mice spontaneously developing breast tumors by 5 months. We then looked at identical TCR sequences in published human studies; we used TCGA data from tumors and healthy tissues of 1,256 breast cancer resections and from 4 focused studies including sequences from tumors, lymph nodes, blood and healthy tissues, and from single cell dataset of 3 breast cancer subjects. We now report that mice spontaneously developing breast cancer manifest shared, Public CDR3 regions in both their alpha and beta and that a significant number of women with early breast cancer manifest identical CDR3 sequences. These findings suggest that the development of breast cancer is associated, across species, with biomarker, exclusive TCR repertoires., Author summary More than 1,100 cancer treatments are currently in clinical testing. Of these, 295 are immune-oncology medicines and vaccines. For Checkpoint Immunotherapy alone, 52,539 patients were enrolled in 2017. Of these treatments, 108 are for breast cancer, the leading cancer diagnosed in women. Although checkpoint immunotherapy has yet to be proven beneficial in most types of breast cancer, current observations of which specific T cell go into the tumor, and how these cells are connected to the response to treatment, have lead to a new understating of the role of the immune system. Yet, and in spite of this intense research into the role of T cells in tumors, very little is known about how clones of T cells behave during tumor formation. The paper we present here studies this clonal behavior over time. We study it during mammary tumor development in mice. We see that a set of T cell clones, which comes from a diversity of different nucleotide sequences, stands out in its behavior compared with other T cell clones. Importantly, we show that these mouse T cell clones have a strong connection to human breast cancer. The specific identification of a subset of T cell clones, together with the behavior of these clones over time, is critical to our understanding of the effect of modifications to the immune system, such as the modifications made by immunotherapy treatments, and to our understanding of how to better control the behavior of the immune system.

N. gonorrhoeae is one of the most pressing antibiotic resistant threats of our time and low-cost diagnostics that can easily identify antibiotic resistance are desperately needed. However, N. gonorrhoeae responds so uniquely to growth conditions that it cannot be assumed gonorrhea will respond to common microbiological methods used for other pathogenic organisms. In this paper, we explore visual colorimetric indicators of N. gonorrhoeae growth that can be seen without a microscope or spectrophotometer. We evaluate growth media, pH indicators, resazurin-based dyes, and tetrazolium-based dyes for their use in simple colorimetric system. Overall, we identified Graver Wade media as the best at supporting robust gonococcal growth while also providing the least background when analyzing results of colorimetric tests. XTT, a tetrazolium-based dye, proved to show to brightest color change over time and not negatively impact the natural growth of N. gonorrhoeae. However, other dyes including PrestoBlue, MTT, and NBT are less expensive than XTT and work well when added after bacterial growth has already occurred. By identifying the specific use cases of these dyes, this research lays the groundwork for future development of a color-based antibiotic susceptibility low-cost test for N. gonorrhoeae.

Refereed/Peer-reviewed Despite the development and success of cochlear implants over several decades, wide inter-subject variability in speech perception is reported. This suggests that cochlear implant user-dependent factors limit speech perception at the individual level. Clinical studies have demonstrated the importance of the number, placement, and insertion depths of electrodes on speech recognition abilities. However, these do not account for all inter-subject variability and to what extent these factors affect speech recognition abilities has not been studied. In this paper, an information theoretic method and machine learning technique are unified in a model to investigate the extent to which key factors limit cochlear implant electrode discrimination. The framework uses a neural network classifier to predict which electrode is stimulated for a given simulated activation pattern of the auditory nerve, and mutual information is then estimated between the actual stimulated electrode and predicted ones. We also investigate how and to what extent the choices of parameters affect the performance of the model. The advantages of this framework include i) electrode discrimination ability is quantified using information theory, ii) it provides a flexible framework that may be used to investigate the key factors that limit the performance of cochlear implant users, and iii) it provides insights for future modeling studies of other types of neural prostheses.

Objective To assess the effects of peri-abortion contraceptive counseling interventions. Methods We performed a systematic review of randomized controlled trials (RCTs) that compared the effect of different types of peri-abortion contraceptive counseling interventions and were published as original papers in scientific journals. The literature search was performed in June 2021 in PubMed, Central Cochrane Library (CENTRAL), Scopus, and Google Scholar; without restrictions in language or publication date. Two independent authors identified studies that met the inclusion and exclusion criteria and extracted the data. The risk of bias was assessed using the Cochrane tool, and evidence certainty was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology. Whenever possible, meta-analyses were performed. The protocol was registered at PROSPERO (CRD42020187354). Results Eleven RCTs were eligible for inclusion (published from 2004 to 2017), from which nine compared enhanced versus standard counseling. Pooled estimates showed that, compared to standard counseling, enhanced counseling was associated with a higher incidence of effective contraceptive use (>3 months) (relative risk [RR], 1.12; 95% confidence interval [CI], 1.09–1.16), although no significant difference was found in the incidence of long-acting reversible contraceptive use (RR, 1.25; 95% CI, 0.68–2.29), contraceptive uptake (RR, 1.06; 95% CI, 0.98–1.15), and obstetric event occurrence (RR, 0.91; 95% CI, 0.57–1.47). Certainty of evidence was very low for all outcomes. In addition, two studies compared contraceptive counseling provided by physicians versus that provided by non-physicians, which did not show significant differences. Conclusions Enhanced contraceptive counseling may favor effective contraceptive use but may not affect the rate of obstetric event occurrence. Also, the studies did not find a difference in the effects of counseling interventions given by different providers. Since evidence certainty was very low, future well-designed RCTs are needed to make informed decisions. Registration The study protocol was registered at PROSPERO (CRD42020187354).

This paper presents a year-long study of our project, aiming at (1) understanding the work practices of clinical staff in trauma intensive care units (TICUs) at a trauma center, with respect to their usage of clinical data interface systems, and (2) developing and evaluating an intuitive and user-centered clinical data interface system for their TICU environments. Based on a long-term field study in an urban trauma center that involved observation-, interview-, and survey-based studies to understand our target users and their working environment, we designed and implemented MediSenseView as a working prototype. MediSenseView is a clinical-data interface system, which was developed through the identification of three core challenges of existing interface system use in a trauma care unit—device separation, usage inefficiency, and system immobility—from the perspectives of three staff groups in our target environment (i.e., doctors, clinical nurses and research nurses), and through an iterative design study. The results from our pilot deployment of MediSenseView and a user study performed with 28 trauma center staff members highlight their work efficiency and satisfaction with MediSenseView compared to existing clinical data interface systems in the hospital.

Objectives The objective of this paper is to study under which circumstances wearable and health app users would accept a compensation payment, namely a digital dividend, to share their self-tracked health data. Methods We conducted a discrete choice experiment alternative, a separated adaptive dual response. We chose this approach to reduce extreme response behavior, considering the emotionally-charged topic of health data sales, and to measure willingness to accept. Previous experiments in lab settings led to demands for high monetary compensation. After a first online survey and two pre-studies, we validated four attributes for the final online study: monthly bonus payment, stakeholder handling the data (e.g., health insurer, pharmaceutical or medical device companies, universities), type of data, and data sales to third parties. We used a random utility framework to evaluate individual choice preferences. To test the expected prices of the main study for robustness, we assigned respondents randomly to one of two identical questionnaires with varying price ranges. Results Over a period of three weeks, 842 respondents participated in the main survey, and 272 respondents participated in the second survey. The participants considered transparency about data processing and no further data sales to third parties as very important to the decision to share data with different stakeholders, as well as adequate monetary compensation. Price expectations resulting from the experiment were high; pharmaceutical and medical device companies would have to pay an average digital dividend of 237.30€/month for patient generated health data of all types. We also observed an anchor effect, which means that people formed price expectations during the process and not ex ante. We found a bimodal distribution between relatively low price expectations and relatively high price expectations, which shows that personal data selling is a divisive societal issue. However, the results indicate that a digital dividend could be an accepted economic incentive system to gather large-scale, self-tracked data for research and development purposes. After the COVID-19 crisis, price expectations might change due to public sensitization to the need for big data research on patient generated health data. Conclusion A continuing success of existing data donation models is highly unlikely. The health care sector needs to develop transparency and trust in data processing. An adequate digital dividend could be an effective long-term measure to convince a diverse and large group of people to share high-quality, continuous data for research purposes.