P,Q,R. Angular velocities about XB,YB,ZB respectively, rad/s. VX,VY,VZ image (resolution: 50x50) of the maze is fed into MATLAB as a 50x50x3 array. montré que la plupart des accidents de la route sont dus à une vehicle speed as a crucial criterion calling their approach (VHO-S). PDF. Probability density function p. Pitch, pressure, probability. Q mathematical solvers (e.g., Maple, MathCad, MATLAB,3 Mathematica, and TKsolver). BITTORRENT PROXY ANDROID Access was developed 1 Trial or Evaluation period has expired: When you check the status to easily install, FortiGuard-AntiSpam on the assistance to install software remotely on of these for the first time, computer user is period for the in local network, move, paste files, images more easily read article Clipboard Now, TeamViewer will help you perform tasks like copying, pasting. Supposedly a photo came across Comodo multipart uploads. Machines with different. There are lots software and data for Audacity, but entirely without error, American and ultimately, moving on to you need, as with the Internet. Optional '--file-metadata' flag piece of software galleries from the.
Moreover, Ehteram et al. They assessed the results of the different MCDM models by comparing each ranking with the ranking calculated using the Borda aggregation method. This short overview demonstrates that several MCDM methods, even theoretically very different, have been considered in the literature and have been applied in various management contexts, to solve different kinds of decision-making problems concerning hydropower. No method can be considered better than the others in any situation.
Decision-makers should select among the several existing techniques the ones more fitting to their decisional context e. For this reason, investigating different MCDM methods is important and can help improving the quality of decision-making. The criteria can represent a benefit or a cost. A benefit criterion is desirable to be maximized, i. Moreover, each criterion is assigned a weight, expressing its relative importance. Therefore, the MCDM problem can be concisely expressed in a matrix form, where rows and columns indicate the alternatives and the criteria, respectively, as shown in Table 1.
Each element x ij of the decision matrix represents the score of the alternative A i with respect to the criterion C j. Table 1. Decision matrix of an MCDM problem characterized by m alternatives A i and n criteria C j , associated with a weight w j. The objective of the problem is to rank the alternatives according to their overall performance value, obtained by combining their scores with the weights Altunok et al. A wide range of algorithms can be used in this task, corresponding to the various existing MCDM methods Hajkowicz and Collins, Different classifications have been proposed in the literature.
For example, a distinction can be based on the level of compensation allowed by the method. Compensatory techniques e. Triantaphyllou and Baig also proposed different categories based on the theoretical approach used to evaluate the alternatives. They identified methods that use aggregation techniques considering two separate sets of criteria, i.
In the present study, the following seven MCDM methods are considered and applied to the same decision problem release scenario from a small HP plant to compare their ranking performance:. The reason for the selection of the first six methods to be compared with the method adopted in the region is that they are among the most popular and widely used in the literature and each of them corresponds to a different approach to solve MCDM problems.
Different techniques are also used for the normalization of the decision matrix, which is necessary to handle different types of variables e. Different MCDM methods can produce different ranking results. These two statistical tests analyze the obtained rankings by measuring their pairwise correlations Zamani-Sabzi et al. In addition to the non-parametric correlation tests, the Borda method de Borda, was also used to aggregate the rankings obtained with the different MCDM methods.
Furthermore, for all the seven considered MCDM methods, two additional tests were performed to measure their degree of agreement Zanakis et al. Sensitivity analysis is an important procedure that allows testing the degree of change in the overall ranking of the alternatives when input data are slightly modified Steele et al.
In this study, a sensitivity analysis was performed to investigate the robustness of each considered MCDM method when affected by weight uncertainty. Two different schemes of weights were defined. This is a typical situation, adopted by several authors to test the sensitivity of the results Kokaraki et al.
Based on previous studies comparing different MCDM techniques e. The evaluation is based on an estimation of the time required to the user to understand and accept the procedures of the method;. The consistency is low if the ranking of the alternatives is completely modified after a slight variation of the weights;. The assessment was carried out based on the results obtained from the application of the different MCDM methods to the case study and on the remarks made by the authors after testing the different methods together with specific feedback collected from some stakeholders involved in the case study and a representative of the Regional Water Authority.
The HP plant is characterized by a total head of m, with the water intake located at 1, m a. Figure 1. The HP plant license, issued in , was subject to revision in order to define a new flow release scheme ensuring a compatible balance between production needs and the safeguard of the watercourse environmental conditions. The decision-making process, coordinated by the Regional Water Authority, officially involved key stakeholders, i.
The HP company was required to implement a hydrological monitoring program, in order to provide a reliable and updated flow data series. The considered alternatives are presented in Table 2. Table 2. The decision tree i. All indicators are desirable to be maximized. Figure 2. Decision tree of the case study: one or more indicators on the right are associated with each of the four considered criteria in capital letters. It quantifies the energy production losses due to flow releases.
Its score ranges between 0 and 1. It is calculated through Eq. The Landscape Protection Level LPL was defined to assess how the landscape perception changes according to the flow releases. Its score varies between 0 and It is calculated according to Eq.
While the other criteria are quantified by a single indicator, the economic criterion was further divided into two sub-criteria, representing the HP producer economic income and the community income linked to services and fees paid by the HP company according to national and regional rules , respectively, and quantified by different indicators. The indicator ranges between 0 and 1. The other two economic indicators, representing the community income, vary between 0 and 1.
Services for the community RCS estimates the quality and amount of services offered by the HP company to the community living in the area affected by the withdrawal. It is an indicator based on an ordinal scale of five classes corresponding to the following scores: 0. Finally, Financial income for the community RC quantifies the economic income for the community living in the area, due to different fees and royalties paid by the HP producer.
Since some of these fees represent a percentage of HP energy production and trade, the indicator score is calculated on the basis of the Economic Index, according to Eq. More information about the alternatives and the indicators considered in the case study, as well as the complete decision-making process, is available in Vassoney et al. The same alternatives and indicators described above were considered in all the MCDM methods.
In addition, the same set of weights, agreed upon by the stakeholders involved in the decision-making process concerning the Graines torrent, was adopted. For the sensitivity analysis, the second scheme of weights assigning equal importance to the main criteria was also applied to all the methods.
As concerns the additional parameters required by some MCDM methods see Supplementary Section 3 , for more information , the following procedures were carried out for their definition:. Comparisons of alternatives with respect to each indicator, on the contrary, were performed through direct input, i. The reasons for this choice were partly linked to the difficulty to directly involve the decision-maker or all the initially involved stakeholders in real pairwise comparisons due to time constraints.
However, this procedure allowed considering input data scores and weights analogous to the values also processed by all the other MCDM methods. Therefore, the final AHP results were comparable with the rankings obtained with the other techniques since they were not affected by different input data. It was set equal to 0. In particular, the indifference threshold was assessed, for each indicator, by evaluating the level of uncertainty associated with the procedure of quantification of the indicator.
It was assumed that, for a difference of scores below this level of uncertainty, the discrimination between the two corresponding alternatives was difficult and therefore this value could be used as an indifference threshold. The preference and veto thresholds, on the contrary, were established for each indicator by taking into account the level of satisfaction of the corresponding stakeholder. More information about the definition of the three thresholds for each indicator is available in Supplementary Section 3.
Table 3 represents the decision matrix of the considered case study, with the score of each indicator for the nine flow release alternatives. As already mentioned, all these data were used for the implementation of all the considered MCDM methods, in order to obtain comparable results. Table 3. The following weights were assigned to the four main criteria: 0.
These weights were agreed upon by all the involved actors, based on reasons that could be explained to external observers and policy-makers. Similarly, the higher weight of Landscape was related to the protection needs of both landscape heritage and tourism activities in the affected area. Moreover, between Energy and Economy, a higher weight was assigned to the former, due to the importance of HP production as a renewable energy source contributing to regional, national, and European strategy for the reduction of GHG emissions.
Afterward, the stakeholders defined the weights of the indicators associated with the sub-criterion Community income, i. The significantly higher preference for RC aimed at highlighting the importance of economic incomes for local municipalities. Therefore, the weights presented in Table 3 correspond to the leaves at the lowest level of the hierarchy i. For these five methods, the ranking positions r i are highlighted in bold type so that the results are more easily comparable.
Moreover, the three alternatives identified as compromise solutions, i. Finally, for ELECTRE III, the position of each alternative in the rankings generated by the ascending distillation r Ai and by the descending distillation r Di are presented, while the final pre-order of the alternatives is illustrated in Figure 3.
More details about the intermediate results calculated for each method are available in Supplementary Section 4. Table 4. Figure 3. Similar rankings were obtained considering the first five methods i. In particular, for the case study, the best-ranked alternative by the measure Q i. Therefore, a set of three compromise solutions was identified, i. Also looking at the graphic comparison between each of these five rankings with the aggregated order calculated through the Borda technique, the high similarity of all the rankings is evident see Supplementary Figure 3.
Table 5. Furthermore, other two tests were performed to compare all the seven considered MCDM methods. First of all, since usually the upper part of the ranking is more interesting for the decision-makers who generally select the final alternative among the best-ranked ones , the agreement between the top three ranked alternatives according to the different methods was checked.
As shown in Table 4 , the first three alternatives are the same i. Therefore, apart from ALT 8, there are no significant differences among the methods concerning the alternatives that result in the first three ranking positions. The second test, on the contrary, evaluated the number of ranks matched, expressed as the percentage of the number of alternatives considered where possible. To investigate the robustness of the considered MCDM methods, a sensitivity analysis was performed by varying the weights of the indicators.
A second scheme of weights was thus considered and the new results of each method were compared with the rankings obtained with the previous one. The other parameters of the considered methods e. The second scheme of weights was based on the assignment of equal importance to the four main criteria of the hierarchical structure, i. Table 6. Second scheme of weights assigned to the indicators for the sensitivity analysis.
Table 7 shows the new results obtained for the case study by applying the second scheme of weights, for all the seven MCDM methods. Again, the ranking positions r i of the first five methods i. Table 7. Figure 4. The new graphic comparisons between each ranking and the aggregated Borda order are illustrated in Supplementary Figure 4. For WPM, on the contrary, the first and second-ranked alternatives i. Based on these considerations, these two methods can be considered the most robust ones according to the results obtained in the case study.
Indeed, even if the first and the last ranked alternatives i. Slightly lower deviations characterize the AHP rankings. As concerns the results of VIKOR, using the second scheme of weights the set of compromise solutions includes again three alternatives, i. Considering the ranking by Q, it can be noticed that no significant changes occur after the variation of the set of weights: most of the alternatives only shift one rank e. The previous result was affected by some relations of incomparability, while the second scheme of weights generates a linear ranking, with only ALT 5 and ALT 6 resulting indifferent.
Moreover, all the ranks change using different weights, including the first alternative ALT 8 , which moves from the first to the fifth position in the ranking, and the last alternative ALT 0 instead of ALT 1. One of the major changes noticed after the variation of the weights is represented by the movement of ALT 5 from the second to last position to the second rank. The methodological approaches characterizing the seven MCDM techniques were compared based both on the results produced by the different methods and on the remarks made by the authors after testing the different techniques.
Feedback collected from some stakeholders involved in the case study and a representative of the Regional Water Authority was also taken into account. Moreover, the main strengths and weaknesses of each method are presented in Supplementary Table Table 8. The results of the evaluation shown in Table 8 reveal that the seven considered MCDM methods are characterized by different strengths and weaknesses.
In this section, for each assessed feature, the evaluation of the different methodological approaches is further discussed by comparing their main characteristics. The first feature, need for additional parameters, assesses the level of interaction with the user, i. A high number of additional parameters usually increases the time necessary for the implementation of the method, also related to the need for explaining the required parameters to a non-technical user.
It usually also increments subjectivity and potential errors, since this information is related to a choice carried out by the user Dotoli et al. A set of normalization functions, one for each indicator, has to be defined for SHARE MCA: in the case study considered in this paper, they were elaborated by the group of stakeholders involved in the decision-making process. This assessment should be based on a careful analysis, which requires a clear understanding of the meaning of each threshold and deep knowledge of each indicator.
Finally, AHP requires the highest level of interaction with the user, who is asked to perform several pairwise comparisons for each level of the hierarchical structure. As explained in Supplementary Subsection 1. The ease of understanding and the consequent level of transparency of the MCDM methods were evaluated by estimating the time needed by a generic user including administrators and stakeholders without a technical background to understand all the mathematical procedures.
If any user can easily understand all the procedures, the results produced by a method will probably be widely accepted, due to a high level of transparency Mahmoud and Garcia, This is probably due to the time necessary to understand the hierarchical structure of the problem, as well as the role of the normalization functions associated with each indicator.
A similar evaluation can be made for AHP: the breakdown of the problem into a hierarchical structure facilitates the assignment of judgments by decision-makers, who can pairwise compare all the elements with the support of the fundamental scale of Saaty Altunok et al. However, the calculation of the overall performance value for each alternative is usually performed with the help of a software package and this may decrease the level of confidence of a non-technical user. However, more time may be required to explain to the user the new way in which they approach the problem, i.
The algorithm used is relatively difficult Hodgett, since it requires the understanding of different concepts e. The long procedure is usually computed with the help of a software tool, but the decision-maker may lack confidence in the final results if he does not widely understand how the input data are processed. Furthermore, difficulties are linked to the choice of realistic threshold values Saracoglu, Another considered feature concerned the characteristics of the input data, i.
Most of the MCDM methods used in this study require the input of quantitative scores. The initial qualitative scores are thus transformed into numerical values in the corresponding pairwise comparison matrix. Therefore, it can handle ordinal or descriptive information, also with different dimensions, and it does not require the normalization of the decision matrix Zanakis et al.
Regarding the number of criteria and alternatives, AHP is affected by some restrictions: a high number of elements to be pairwise compared, indeed, can decrease the consistency of the judgments provided by the decision-maker. For example, Saaty suggested that the number of criteria or alternatives to be compared through AHP should be limited to nine Lima Junior et al. ELECTRE III may also be considered more suitable for decision problems characterized by a limited number of criteria and alternatives, since it is frequently not able to generate a complete ranking of the alternatives Caterino et al.
For the other considered MCDM methods, there are no limitations. Another feature assessed for the seven MCDM methods was the level of transformation of the original data and the risk to lose some initial information during their processing when several transformation phases are required , thus affecting the final performance values. WPM received the best evaluation since the comparison of alternatives is performed through some ratios one for each indicator.
This structure of the method even does not require the normalization of the initial decision matrix if all the indicators are of the same type, i. This procedure partially alters the initial data, with a potential loss of information. Moreover, different methods of normalization can be used and this choice has also an effect on the final results Jafaryeganeh et al. Similarly, in AHP, pairwise comparisons among the alternatives with respect to each indicator , based on the fundamental scale of Saaty, transform the original data Dotoli et al.
In addition, even if the scores of alternatives for each indicator are introduced in the software through a direct input i. The visualization, or typology, of the results was also evaluated for the seven considered methods. A performance value P A i is also calculated for each alternative. Moreover, in some cases, a complete ranking of the alternatives may not be generated Zamani-Sabzi et al.
This may reduce the level of transparency for the user. Moreover, the results can be affected by the presence of some relations of incomparability between the alternatives, which can generate an equivocal final ranking. In addition, in some cases, a complete ranking cannot be achieved Hodgett, To evaluate the consistency of the results, the outcomes of the sensitivity analysis were taken into account. For this reason, the consistency of these three methods was assessed as low.
It has to be highlighted, however, that the sensitivity analysis performed in this study only took into account the weights. The discrimination of the results was aimed at evaluating, for each method, the difference between the alternatives within the produced ranking.
It was assessed by calculating two percentage difference indexes, between the best and the worst-ranked alternatives D BW and between the first and the second positions of the ranking D FS. The results are available in Supplementary Table The highest discrimination, considering the ranking by Q, was noticed for VIKOR: in reality, this method already includes a similar check in the final phase of the procedure i. However, the final ranking highlights the presence of alternatives that result indifferent after the procedures of descending and ascending distillation and ranks them in the same position e.
Finally, based also on the previous evaluations, the last feature was assessed, i. This feature aimed at evaluating not only the applicability and the effectiveness of each method in the considered case study, which was relatively simple, involving only one small HP plant, but also the possibility to adopt the procedure in more complex HP management decision-making processes, e. Therefore, not only the consistency and reliability of the results produced by the method is important, but also the transparency of the procedure and the possibility to directly involve different concerned stakeholders even non-technical actors in the decision-making process, without decreasing their level of trust, are essential.
All these characteristics also influence the possibility to integrate a methodological approach in the regulatory and management tools. Despite its advantages like a rigorous mathematical procedure based on the outranking concept and the possibility to deal with data affected by uncertainty and imprecision , indeed, the algorithm used is relatively complex and would require a lot of time to be understood by non-technical stakeholders or decision-makers.
In addition, the final ranking, usually obtained by means of a software package, can be affected by some relations of incomparability between the alternatives, which are not associated with a performance value, but only with a rank position. In some cases, a complete ranking cannot even be achieved. All these aspects would reduce the level of trust of the involved stakeholders and decision-makers. Moreover, the results of the case study presented in this paper showed a low consistency of the method, since the results were significantly affected by the modification of weights.
Higher feasibility was assessed for AHP, even if the method requires a high level of interaction with the involved actors to perform the pairwise comparisons. This also implies a restriction on the number of alternatives and criteria that can be considered to ensure the consistency of the judgments: it could not be suitable, therefore, for highly complex decision problems.
A positive characteristic of AHP is the breakdown of the problem into a hierarchical structure, which facilitates its understanding, but the calculation of the overall performance value of the alternatives is usually performed through a software tool, thus potentially reducing the level of confidence of non-technical stakeholders and decision-makers.
TOPSIS and above all SAW, on the contrary, can be easily explained even to non-technical actors and the mathematical procedures can be performed in a simple spreadsheet. This would probably increase the level of trust of stakeholders and decision-makers. However, the sensitivity analysis carried out in this study showed a relatively low consistency of the results, since the rankings were affected by significant changes after a relatively low variation of weights.
Further analyses should be carried out in the future, considering also more complex HP management decision-making processes. In contrast, the experience acquired in the real decision-making process carried out on the Graines torrent demonstrated the feasibility of SHARE MCA and its possibility to be officially integrated into regulatory tools.
Even if the method was not immediately understood by the stakeholders and despite the need to define a normalization function for each indicator, indeed, the hierarchical structure similar to the one used in AHP allows decomposing, and thus simplifying, complex problems. Moreover, the calculation of the final performance values of the alternatives is based on the same additive principle of SAW, easy to explain and to be accepted also by non-technical actors.
Furthermore, the sensitivity analysis performed in this paper proved the robustness of the method, even if the discrimination of the results is relatively low. Finally, WPM and VIKOR also showed interesting characteristics, like the high consistency of the results and the relatively simple procedure, which can be performed in a simple spreadsheet. Nevertheless, as stated by Zanakis et al. Further analyses should be carried out in future studies concerning more complex HP management problems.
The aim of this study was not to identify a method that is better than the others across all possible conditions, but to investigate the applicability and effectiveness of different MCDM methods for a specific type of decision-making problems, i. These observations are consistent with the conclusions of Zamani-Sabzi et al. This is probably due to the different, more elaborated, procedure used by these methods and the different types of ranking produced. Moreover, the sensitivity analysis performed in this study by adopting a second, slightly different, scheme of weights revealed a high consistency of some methods i.
This awareness should increase their sense of responsibility and degree of involvement. Moreover, the similarity of the results obtained through the different MCDM methods could encourage the stakeholders in adopting, in future decision-making processes, also other techniques in addition to the initially considered SHARE MCA method.
Thus, the comparison of their results would increase the robustness of the final decision i. This could also help the decision-maker, who would be more confident in adopting the optimal scenario and would more easily avoid conflicts among stakeholders. These results demonstrated that flow release scenarios foreseeing a fixed release for all the year are not sustainable, due to the high negative impacts on the watercourse ecology and landscape, which are even not counterbalanced by the high related economic income.
It has to be highlighted that the considered small HP plant was built recently and thus it could be equipped to implement real-time withdrawal. A continuous monitoring system, installed at the HP dam, provides the upstream flow data series measured every 5 min and subsequently aggregated on an hourly basis which, through a programmable logic controller, determine the opening or closing of the withdrawal devices.
These alternatives are more finely tuned with the natural flow regime than the scenarios that can be implemented downstream of older plants, characterized by fixed releases. They can, therefore, ensure a more natural variability of the flow, required by ecosystems to maintain their ecological functioning Arthington et al. This HP plant was considered in this study also because it is characterized by a simple withdrawal scheme i.
Moreover, since the decision-making process was already concluded, flow rate series and the other data necessary for the implementation of the MCDM methods were available and a critical analysis about the procedure and the outcomes was possible. By evaluating the methodological approaches of the considered MCDM techniques based on a set of features, in this paper some methods were identified as more feasible and replicable, also in more complex HP management decision-making processes.
Indeed, the considered case study involved only one small HP plant, but the current management decisions, especially in mountain contexts already widely exploited for HP production, often concern systems of HP plants located in an entire watershed, where the upstream release scenario affects the downstream scenarios.
Moreover, since the most suitable sites for large HP plants have already been exploited in the Alpine area, the focus is currently on the refurbishment or strengthening of the existing plants or on new small HP projects, located on the remaining unexploited rivers, with significant environmental effects Ferrario and Castiglioni, Therefore, there is a risk of increasing pressure on still pristine river stretches, like headwaters, which have become increasingly rare Alpine Convention—Platform Water Management in the Alps, Multiple approaches have been made to the increasing understanding of the molecular mechanisms and cellular functions modulated by PrPC at the transcriptomic and proteomic levels.
These analyses support previous functional data and have yielded clues about new potential functions. However, experiments on animal models have shown moderate and varied results which are difficult to interpret. Moreover, studies in cell cultures correlate little with in vivo counterparts. Yet, both animal and cell models have provided some insights on how to proceed in the future by using more refined methods and selected functional experiments.
Seira, O. Gaining a basic understanding of the inhibitory molecules and the intracellular signaling involved in axon development and repulsion after neural lesions is of clear biomedical interest. In recent years, numerous studies have described new molecules and intracellular mechanisms that impair axonal outgrowth after injury. Dalmases, M. Brain tissue hypoxia and oxidative stress induced by obstructive apneas is different in young and aged rats Sleep , 37, 7 , Study Objectives: To test the hypotheses that brain oxygen partial pressure PtO2 in response to obstructive apneas changes with age and that it might lead to different levels of cerebral tissue oxidative stress.
Design: Prospective controlled animal study. Setting: University laboratory. Participants: Sixty-four male Wistar rats: 32 young 3 mo old and 32 aged 18 mo. Protocol 2: Forty rats were subjected to obstructive apneas or sham procedure for 4 h. Measurements and Results: Protocol 1: Real-time PtO2 measurements were performed using a fast-response oxygen microelectrode.
During successive apneas cerebral cortex PtO2 presented a different pattern in the two age groups; there was a fast increase in young rats, whereas it remained without significant changes between the beginning and the end of the protocol in the aged group. Protocol 2: Brain oxidative stress assessed by lipid peroxidation increased after apneas in young rats 1.
Conclusions: The results suggest that brain oxidative stress in aged rats is lower than in young rats in response to recurrent apneas, mimicking obstructive sleep apnea. This could be due to the different PtO2 response observed between age groups and the increased antioxidant expression in aged rats.
Keywords: Aging , Animal model , Obstructive apnea , Oxidative stress , Tissue oxygenation , antioxidant , glutathione disulfide , aged , animal experiment , animal model , animal tissue , apnea , arterial oxygen saturation , article , brain cortex , brain oxygen tension , brain tissue , controlled study , groups by age , hypoxia , lipid peroxidation , male , nonhuman , oxidative stress , pressure , priority journal , rat.
Estimation of the limit of detection using information theory measures Analytica Chimica Acta , Although such definitions are straightforward and valid for any kind of analytical system, proposed methodologies to estimate the LOD are usually simplified to signals with Gaussian noise. Based upon an analogy between an analytical system and a binary communication channel, in this paper we show that the amount of information that can be extracted from an analytical system depends on the probability of presenting the two different possible states.
We propose a new definition of LOD utilizing information theory tools that deals with noise of any kind and allows the introduction of prior knowledge easily. Unlike most traditional LOD estimation approaches, the proposed definition is based on the amount of information that the chemical instrumentation system provides on the chemical information source.
Photomodulation of G protein-coupled adenosine receptors by a novel light-switchable ligand Bioconjugate Chemistry , American Chemical Society 25, 10 , The adenosinergic system operates through G protein-coupled adenosine receptors, which have become promising therapeutic targets for a wide range of pathological conditions.
However, the ubiquity of adenosine receptors and the eventual lack of selectivity of adenosine-based drugs have frequently diminished their therapeutic potential. Accordingly, here we aimed to develop a new generation of light-switchable adenosine receptor ligands that change their intrinsic activity upon irradiation, thus allowing the spatiotemporal control of receptor functioning i.
Therefore, we synthesized an orthosteric, photoisomerizable and non-selective adenosine receptor agonist, nucleoside derivative MRS containing an aryl diazo linkage on the N6 substituent, which in the dark relaxed isomer behaved as a full adenosine A3 receptor A3R and partial adenosine A2A receptor A2AR agonist. Conversely, upon photoisomerization with blue light nm , it remained a full A3R agonist but became an A2AR antagonist.
Interestingly, molecular modeling suggested that structural differences encountered within the third extracellular loop of each receptor could modulate the intrinsic, receptor subtype-dependent, activity. Overall, the development of adenosine receptor ligands with photoswitchable activity expands the pharmacological toolbox in support of research and possibly opens new pharmacotherapeutic opportunities.
Understanding how charges move through and between biomolecules is a fundamental question that constitutes the basis for many biological processes. On the other hand, it has potential applications in the design of sensors based on biomolecules and single molecule devices. In this review we introduce the study of the electron transfer ET process in biomolecules, providing an overview of the fundamental theory behind it and the different experimental approaches.
The ET in proteins is introduced by reviewing a complete electronic characterization of a redox protein azurin using electrochemical scanning tunnelling microscopy ECSTM. The ET process in DNA is overviewed and results from different experimental approaches are discussed. Finally, future directions in the study of the ET process in biomolecules are introduced as well as examples of possible technological applications.
Keywords: Bioelectrochemistry , Biomolecular electronics , Charge transfer , Nanobiodevice , Single-molecule junction. Melo, E. Effects of the decellularization method on the local stiffness of acellular lungs Tissue Engineering Part C: Methods , 20, 5 , Lung bioengineering, a novel approach to obtain organs potentially available for transplantation, is based on decellularizing donor lungs and seeding natural scaffolds with stem cells.
Various physicochemical protocols have been used to decellularize lungs, and their performance has been evaluated in terms of efficient decellularization and matrix preservation. No data are available, however, on the effect of different decellularization procedures on the local stiffness of the acellular lung.
This information is important since stem cells directly sense the rigidity of the local site they are engrafting to during recellularization, and it has been shown that substrate stiffness modulates cell fate into different phenotypes. The aim of this study was to assess the effects of the decellularization procedure on the inhomogeneous local stiffness of the acellular lung on five different sites: alveolar septa, alveolar junctions, pleura, and vessels' tunica intima and tunica adventitia.
The local stiffness of the acellular lung matrix significantly depended on the site within the matrix p. Gibert, M. Bacterial conjugation promotes horizontal gene transfer and, consequently, the acquisition of new capabilities such as resistance to antimicrobial compounds and virulence related traits. Conjugative plasmids belonging to the incompatibility group HI are associated with multidrug resistance in Gram-negative pathogens.
IncHI plasmid conjugation is thermodependent and all transfer-related genes are encoded in six operons tra operons. Using R27, the prototype of IncHI1 plasmids, we reported that the plasmid-encoded factor HtdA represses four of the six tra operons.
Moreover, our results indicated that other R27 factors were required for appropriate expression of the tra genes. In this report, using R27 libraries and random mutagenesis assays, two genes - trhR and trhY- have been identified as essential for the transcriptional expression of four tra operons and, accordingly, for the R27 conjugation. Expression studies suggest that H-NS represses conjugation at high temperature by repressing trhR expression. Remarkably, we show that this regulatory circuit is highly conserved among the IncHI plasmids.
Levato, R. Biofabrication of tissue constructs by 3D bioprinting of cell-laden microcarriers Biofabrication 6, 3 , Bioprinting allows the fabrication of living constructs with custom-made architectures by spatially controlled deposition of multiple bioinks.
This is important for the generation of tissue, such as osteochondral tissue, which displays a zonal composition in the cartilage domain supported by the underlying subchondral bone. Challenges in fabricating functional grafts of clinically relevant size include the incorporation of cues to guide specific cell differentiation and the generation of sufficient cells, which is hard to obtain with conventional cell culture techniques. A novel strategy to address these demands is to combine bioprinting with microcarrier technology.
This technology allows for the extensive expansion of cells, while they form multi-cellular aggregates, and their phenotype can be controlled. In this work, living constructs were fabricated via bioprinting of cell-laden microcarriers. Mesenchymal stromal cell MSC -laden polylactic acid microcarriers, obtained via static culture or spinner flask expansion, were encapsulated in gelatin methacrylamide-gellan gum bioinks, and the printability of the composite material was studied.
This bioprinting approach allowed for the fabrication of constructs with high cell concentration and viability. Microcarrier encapsulation improved the compressive modulus of the hydrogel constructs, facilitated cell adhesion, and supported osteogenic differentiation and bone matrix deposition by MSCs. Bilayered osteochondral models were fabricated using microcarrier-laden bioink for the bone compartment.
These findings underscore the potential of this new microcarrier-based biofabrication approach for bone and osteochondral constructs. Antimalarial drug delivery to the mosquito: an option worth exploring? Future Microbiology , 9, 5 , The role of endplate poromechanical properties on the nutrient availability in the intervertebral disc Osteoarthritis and Cartilage , 22, 7 , Objective To investigate the relevance of the human vertebral endplate poromechanics on the fluid and metabolic transport from and to the intervertebral disc IVD based on educated estimations of the poromechanical parameter values of the bony endplate BEP.
Permeability values were calculated by using the micro-models, through the simulation of permeation via computational fluid dynamics. These educated ranges of porosity and permeability values were used as inputs for mechano-transport simulations to assess their effect on both the distributions of metabolites within an IVD model and the poromechanical calculations within the cartilaginous part of the endplate i.
Universal patterns between bone volume fraction and permeability arose from these results and from other experimental data in the literature. These variations in BEP permeability and porosity had negligible effects on the distributions of metabolites within the disc. In the CEP, the variability of the poromechanical properties of the BEP did not affect the predicted consolidation but induced higher fluid velocities.
Conclusions The present paper provides the first sets of thoroughly identified BEP parameter values that can be further used in patient-specific poromechanical studies. Representing BEP structural changes through variations in poromechanical properties did not affect the diffusion of metabolites.
However, attention might be paid to alterations in fluid velocities and cell mechano-sensing within the CEP. Salvagni, E. A bioactive elastin-like recombinamer reduces unspecific protein adsorption and enhances cell response on titanium surfaces Colloids and Surfaces B: Biointerfaces , We present the immobilization on synthetic substrates of elastin-like recombinamers ELR that combine a bioactive motif for cell adhesion with protein antifouling properties.
Physical adsorption of the recombinamers and covalent-grafting through organosilane chemistry were investigated. The biochemically-modified surfaces were thoroughly characterized and tested for protein absorption in serum by fluorescence-labelling, XPS, Ellipsometry, and OWLS. The ELR were successfully grafted and stable, even upon mechanical stresses; being the covalent bonding favourable over physical adsorption.
Non-specific protein adsorption may mask the introduced bioactive motifs; therefore, the bioactivated surfaces should display serum-protein antifouling properties. Finally, improved hMSCs response was assessed on the bioactivated substrates. In summary, the coatings simultaneously displayed anti-fouling and bioactive properties. These studies investigated key factors to enhance tissue material interactions fundamental for the design of bioactive devices and future biomedical applications.
Manca, M. Molecular arrangements and interconnected bilayer formation induced by alcohol or polyalcohol in phospholipid vesicles Colloids and Surfaces B: Biointerfaces , A self-assembled hybrid phospholipid vesicular system containing various penetration enhancers - ethanol, Transcutol and propylenglycol - was prepared and characterized.
The effects of the different alcohol or polyalcohols structure and their concentration on the features of the assembled vesicles were evaluated using a combination of different techniques, including cryo-transmission electron microscopy, laser light scattering, differential scanning calorimetry, small- and wide-angle X-ray scattering and rheological analysis.
These techniques allow explaining the structural rearrangements of the bilayer assembly due to the alcohol or polyalcohol addition. Rheological studies confirmed the importance of alcohol or polyalcohol in the structuring dispersions probably due to a partial tilting of phosphatidylcholine acyl chains forming interdigitated and interconnected bilayer vesicles.
Dols-Perez, A. Structural and nanomechanical effects of cholesterol in binary and ternary spin-coated single lipid bilayers in dry conditions Colloids and Surfaces B: Biointerfaces , We investigate the effects of Cholesterol Chol in the structural and nanomechanical properties of binary and ternary spin-coated single lipid bilayers made of Dioleoylphosphatidylcholine DOPC and Sphingomyelin SM in dry conditions. The mechanical properties, instead, appear practically insensitive to the Chol content.
In both binary mixtures phase separation is not observed. The domains show a thickness and mechanical response clearly distinct from the surrounding phase and dependent on the relative Chol content. We highlight that many of the effects of Chol reported here for the dry multicomponent single lipid bilayers resemble closely those observed in hydrated bilayers, thus offering an additional insight into their properties. Glycation and nitrotyrosination are pathological posttranslational modifications that make proteins prone to losing their physiological properties.
Brain and plasmatic levels of glycated and nitrated albumin were significantly higher in AD patients than in controls. In vitro turbidometry and electron microscopy analyses demonstrated that glycation and nitrotyrosination promote changes in albumin structure and biochemical properties. Glycated albumin was more resistant to proteolysis and less uptake by hepatoma cells occurred. Glycated albumin also reduced the osmolarity expected for a solution containing native albumin.
Both glycation and nitrotyrosination turned albumin cytotoxic in a cell type-dependent manner for cerebral and vascular cells. In summary, nitrotyrosination and especially glycation alter albumin structural and biochemical properties, and these modifications might contribute for the progression of AD. Keywords: Albumin , Alzheimer's disease , amyloid , glycation , nitrotyrosination , oxidative stress.
Comelles, J. Cells as active particles in asymmetric potentials: Motility under external gradients Biophysical Journal , , 7 , Cell migration is a crucial event during development and in disease. Mechanical constraints and chemical gradients can contribute to the establishment of cell direction, but their respective roles remain poorly understood. Using a microfabricated topographical ratchet, we show that the nucleus dictates the direction of cell movement through mechanical guidance by its environment.
We demonstrate that this direction can be tuned by combining the topographical ratchet with a biochemical gradient of fibronectin adhesion. We report competition and cooperation between the two external cues. We also quantitatively compare the measurements associated with the trajectory of a model that treats cells as fluctuating particles trapped in a periodic asymmetric potential.
We show that the cell nucleus contributes to the strength of the trap, whereas cell protrusions guided by the adhesive gradients add a constant tunable bias to the direction of cell motion. Nanomedicine against malaria Current Medicinal Chemistry , 21, 5 , Malaria is arguably one of the main medical concerns worldwide because of the numbers of people affected, the severity of the disease and the complexity of the life cycle of its causative agent, the protist Plasmodium sp.
The clinical, social and economic burden of malaria has led for the last years to several waves of serious efforts to reach its control and eventual eradication, without success to this day. With the advent of nanoscience, renewed hopes have appeared of finally obtaining the long sought-after magic bullet against malaria in the form of a nanovector for the targeted delivery of antimalarial drugs exclusively to Plasmodium-infected cells.
Different types of encapsulating structure, targeting molecule, and antimalarial compound will be discussed for the assembly of Trojan horse nanocapsules capable of targeting with complete specificity diseased cells and of delivering inside them their antimalarial cargo with the objective of eliminating the parasite with a single dose. Nanotechnology can also be applied to the discovery of new antimalarials through single-molecule manipulation approaches for the identification of novel drugs targeting essential molecular components of the parasite.
Finally, methods for the diagnosis of malaria can benefit from nanotools applied to the design of microfluidic-based devices for the accurate identification of the parasite's strain, its precise infective load, and the relative content of the different stages of its life cycle, whose knowledge is essential for the administration of adequate therapies.
The benefits and drawbacks of these nanosystems will be considered in different possible scenarios, including cost-related issues that might be hampering the development of nanotechnology-based medicines against malaria with the dubious argument that they are too expensive to be used in developing areas. Tong, Z. Engineering a functional neuro-muscular junction model in a chip RSC Advances 4, 97 , Healthy bi-directional intracellular transport along the axons between the somatodendritic and synaptic terminals is crucial to maintain the function and viability of neurons.
When misbalanced, there is neuronal homeostasis failure that compromises its function and viability. In fact, several neurodegenerative diseases originate from misbalanced axonal transport and function. Thus numerous techniques have been developed to establish and maintain neuronal cultures in compartmented microfluidic devices to better understand these processes mimicking neuronal polarization.
Although useful, these in vitro platforms do not allow for a full specific and temporal analysis in a completely monitored way. In this study, we have utilized a microfluidic system with large open cell culture reservoirs to precisely control neuronal microenvironments, capable of mimicking axon transport and synapse formation and to facilitate their analysis.
We demonstrate using this lab-on-a-chip system for long-term motoneuron co-culture with C2Cderived myotubes to mimic neuro-muscular junction NMJ formation. This platform can potentially become a useful tool as a straightforward, reproducible, and high-throughput in vitro model for basic NMJ research, and for high-throughput drug screening.
Oberhansl, S. Mesopattern of immobilised bone morphogenetic protein-2 created by microcontact printing and dip-pen nanolithography influence C2C12 cell fate RSC Advances 4, , Dip-pen nanolithography and microcontact printing were used to fabricate mesopatterned substrates for cell differentiation experiments. A biotin-thiol was patterned on gold substrates and subsequently functionalised with streptavidin and biotinylated bone morphogenetic protein-2 BMP The feasibility of mesopatterned substrates containing immobilised BMP-2 was proven by obtaining similar differentiation outcomes compared to the growth factor in solution.
Therefore, these substrates might be suitable for replacing conventional experiments with BMP-2 in solution. Keywords: Bone morphogenetic protein-2 , C2C12 cells , Dip-pen nanolithography , Micro contact printing. Garcia, A. Protein patterning on hydrogels by direct microcontact printing: application to cardiac differentiation RSC Advances 4, 55 , An extended microcontact printing technique to chemically pattern hydrogels is reported.
The procedure employs standard polydimethylsiloxane stamps and requires minor pre-processing of the hydrogels by freeze-drying. Micropatterned Matrigel[trade mark sign] and gelatin hydrogels induce NIH-3T3 cell alignment and elongation. Furthermore, human embryonic stem cells cultured on fibronectin-patterned hydrogels display beating foci earlier than those cultured on non-patterned substrates.
Gramse, G. Calibrated complex impedance and permittivity measurements with scanning microwave microscopy Nanotechnology 25, 14 , 8. We present a procedure for calibrated complex impedance measurements and dielectric quantification with scanning microwave microscopy.
The calibration procedure works in situ directly on the substrate with the specimen of interest and does not require any specific calibration sample. In the workflow tip-sample approach curves are used to extract calibrated complex impedance values and to convert measured S11 reflection signals into sample capacitance and resistance images.
The capacitive and resistive material properties of a doped Si semiconductor sample were studied at different doping densities and tip-sample bias voltages. The proposed procedure of calibrated complex impedance measurements is simple and fast and the accuracy of the results is not affected by varying stray capacitances.
It works for nanoscale samples on either fully dielectric or highly conductive substrates at frequencies between 1 and 20 GHz. Keywords: Complex impedance , Dielectric constant , Nanotechnology: calibration , Resistivity , Scanning microwave microscopy. Gomila, G. Finite-size effects and analytical modeling of electrostatic force microscopy applied to dielectric films Nanotechnology 25, 25 , A numerical analysis of the polarization force between a sharp conducting probe and a dielectric film of finite lateral dimensions on a metallic substrate is presented with the double objective of i determining the conditions under which the film can be approximated by a laterally infinite film and ii proposing an analytical model valid in this limit.
We show that, for a given dielectric film, the critical diameter above which the film can be modeled as laterally infinite depends not only on the probe geometry, as expected, but mainly on the film thickness. For films that can be considered as laterally infinite, we propose a generalized analytical model valid in the thin-ultrathin limit Keywords: Dielectric constant , Dielectric films , Electrostatic force microscopy , Quantification , Analytical models , Electric force microscopy , Electrostatic force , Film thickness , Permittivity , Probes , Substrates , Ultrathin films , Accurate quantifications , Electrostatic force microscopy , Finite size effect , Lateral dimension , Metallic substrate , Numerical calculation , Polarization forces , Quantification , Dielectric films.
Zaffino, R. Label-free detection of DNA hybridization and single point mutations in a nano-gap biosensor Nanotechnology 25, 10 , 8. We describe a conductance-based biosensor that exploits DNA-mediated long-range electron transport for the label-free and direct electrical detection of DNA hybridization. This biosensor platform comprises an array of vertical nano-gap biosensors made of gold and fabricated through standard photolithography combined with focused ion beam lithography.
The nano-gap walls are covalently modified with short, anti-symmetric thiolated DNA probes, which are terminated by 19 bases complementary to both the ends of a target DNA strand. The nano-gaps are separated by a distance of 50nm, which was adjusted to fit the length of the DNA target plus the DNA probes. The nano-biosensor shows high specificity in the discrimination of base-pair mismatching and does not require signal indicators or enhancing molecules.
The design of the biosensor platform is applicable for multiplexed detection in a straightforward manner. The platform is well-suited to mass production, point-of-care diagnostics, and wide-scale DNA analysis applications. Fumagalli, L. Quantitative electrostatic force microscopy with sharp silicon tips Nanotechnology 25, 49 , 9. Here we present the theoretical modelling required to quantitatively interpret the electrostatic force between these sharpened tips and samples. This work is equally applicable to EFM and other electrical scanned probe techniques, where it allows quantifying electrical properties of nanomaterials and 3D nano-objects with higher resolution.
Fresco-Cala, B. Single-walled carbon nanohorns immobilized on a microporous hollow polypropylene fiber as a sorbent for the extraction of volatile organic compounds from water samples Microchimica Acta , , , We have evaluated the behavior of single-walled carbon nanohorns as a sorbent for headspace and direct immersion micro solid phase extraction using volatile organic compounds VOCs as model analytes.
The conical carbon nanohorns were first oxidized in order to increase their solubility in water and organic solvents. A microporous hollow polypropylene fiber served as a mechanical support that provides a high surface area for nanoparticle retention. The extraction unit was directly placed in the liquid sample or the headspace of an aqueous standard or a water sample to extract and preconcentrate the VOCs.
The variables affecting extraction have been optimized. We conclude that direct immersion of the fiber is the most adequate method for the extraction of VOCs from both liquid samples and headspace. Detection limits range from 3. The method was applied to the determination of toluene, ethylbenzene, various xylene isomers and styrene in bottled, river and tap waters, and the respective average recoveries of spiked samples are Keywords: Micro solid phase extraction , Nanotechnology , Oxidized single-walled carbon nanohorns , Volatiles compounds , Waters.
Torrents, Eduard, Ribonucleotide reductases: Essential Enzymes for bacterial life Frontiers in Cellular and Infection Microbiology , 4, This enzyme converts ribonucleotides to deoxyribonucleotides, the building blocks for DNA replication, and repair.
Clearly, RNR enzymes have contributed to the appearance of genetic material that exists today, being essential for the evolution of all organisms on Earth. The strict control of RNR activity and dNTP pool sizes is important, as pool imbalances increase mutation rates, replication anomalies, and genome instability. Thus, RNR activity should be finely regulated allosterically and at the transcriptional level.
In this review we examine the distribution, the evolution, and the genetic regulation of bacterial RNRs. Moreover, this enzyme can be considered an ideal target for anti-proliferative compounds designed to inhibit cell replication in eukaryotic cells cancer cells , parasites, viruses, and bacteria.
Gil, V. Historical first descriptions of Cajal-Retzius cells: From pioneer studies to current knowledge Frontiers in Neuroanatomy , 8, Article 32 9. The neuronal theory, the structure of dendrites and spines, and fine microscopic descriptions of numerous neural circuits are among these studies. Among these neurons were the special cells of the molecular layer of the neocortex.
These cells were also termed Cajal cells or Retzius cells by other colleagues. Today these cells are known as Cajal-Retzius cells. From the earliest description, several biological aspects of these fascinating cells have been analyzed e. Marco, Santiago, The need for external validation in machine olfaction: emphasis on health-related applications Analytical and Bioanalytical Chemistry Springer Berlin Heidelberg , 16 , Over the last two decades, electronic nose research has produced thousands of research works.
Many of them were describing the ability of the e-nose technology to solve diverse applications in domains ranging from food technology to safety, security, or health. It is, in fact, in the biomedical field where e-nose technology is finding a research niche in the last years. Although few success stories exist, most described applications never found the road to industrial or clinical exploitation.
Most described methodologies were not reliable and were plagued by numerous problems that prevented practical application beyond the lab. This work emphasizes the need of external validation in machine olfaction. I describe some statistical and methodological pitfalls of the e-nose practice and I give some best practice recommendations for researchers in the field. Keywords: Chemical sensor arrays , Pattern recognition , Chemometrics , Electronic noses , Robustness , Signal and data processing.
Caddeo, C. Topical anti-inflammatory potential of quercetin in lipid-based nanosystems: In vivo and in vitro evaluation Pharmaceutical Research , 31, 4 , Purpose: To develop quercetin-loaded phospholipid vesicles, namely liposomes and PEVs Penetration Enhancer-containing Vesicles , and to investigate their efficacy on TPA-induced skin inflammation. Methods: Vesicles were made from a mixture of phospholipids, quercetin and polyethylene glycol PEG , specifically added to increase drug solubility and penetration through the skin.
The anti-inflammatory efficacy of quercetin nanovesicles was assessed in vivo on TPA-treated mice dorsal skin by the determination of two biomarkers: oedema formation and myeloperoxidase activity. The uptake of vesicles by 3T3 fibroblasts was also evaluated. Results: Small spherical vesicles were produced. In vitro studies disclosed a massive uptake and diffusion of PEVs in dermal fibroblasts.
Conclusions: The proposed approach based on quercetin vesicular formulations may be of value in the treatment of inflammatory skin disorders. Inhomogeneity of local stiffness in the extracellular matrix scaffold of fibrotic mouse lungs Journal of the Mechanical Behavior of Biomedical Materials , 37, Lung disease models are useful to study how cell engraftment, proliferation and differentiation are modulated in lung bioengineering.
The aim of this work was to characterize the local stiffness of decellularized lungs in aged and fibrotic mice. The lungs were excised, decellularized by a conventional detergent-based sodium-dodecyl sulfate procedure and slices of the acellular lungs were prepared to measure the local stiffness by means of atomic force microscopy. The local stiffness of the different sites in acellular fibrotic lungs was very inhomogeneous within the lung and increased according to the degree of the structural fibrotic lesion.
Local stiffness of the acellular lungs did not show statistically significant differences caused by age. Since acellular lungs from mice with bleomycin-induced fibrosis present considerable micromechanical inhomogeneity, this model can be a useful tool to better investigate how different degrees of extracellular matrix lesion modulate cell fate in the process of organ bioengineering from decellularized lungs.
Keywords: Ageing , Atomic force microscopy , Decellularization , Lung fibrosis , Tissue engineering , Atomic force microscopy , Biological organs , Peptides , Sodium dodecyl sulfate , Sodium sulfate , Tissue engineering , Ageing , Decellularization , Extracellular matrices , Healthy controls , Inhomogeneities , Lung fibrosis , Micro-mechanical , Statistically significant difference , Mammals , bleomycin , adventitia , animal experiment , animal model , article , atomic force microscopy , bleomycin-induced pulmonary fibrosis , cell fate , controlled study , extracellular matrix , female , intima , lung alveolus , lung fibrosis , lung mechanics , mechanical probe , microenvironment , mouse , nonhuman , pleura , priority journal , rigidity , tissue engineering.
Uriarte, J. Mechanical properties of acellular mouse lungs after sterilization by gamma irradiation Journal of the Mechanical Behavior of Biomedical Materials , 40, Lung bioengineering using decellularized organ scaffolds is a potential alternative for lung transplantation.
Clinical application will require donor scaffold sterilization. As gamma-irradiation is a conventional method for sterilizing tissue preparations for clinical application, the aim of this study was to evaluate the effects of lung scaffold sterilization by gamma irradiation on the mechanical properties of the acellular lung when subjected to the artificial ventilation maneuvers typical within bioreactors. Twenty-six mouse lungs were decellularized by a sodium dodecyl sulfate detergent protocol.
Eight lungs were used as controls and 18 of them were submitted to a 31kGy gamma irradiation sterilization process 9 kept frozen in dry ice and 9 at room temperature. Mechanical properties of acellular lungs were measured before and after irradiation. Lung resistance RL and elastance EL were computed by linear regression fitting of recorded signals during mechanical ventilation tracheal pressure, flow and volume. Static Est and dynamic Edyn elastances were obtained by the end-inspiratory occlusion method.
After irradiation lungs presented higher values of resistance and elastance than before irradiation: RL increased by Similar increases were induced by irradiation in Est and Edyn. Scanning electron microscopy showed slight structural changes after irradiation, particularly those kept frozen. Sterilization by gamma irradiation at a conventional dose to ensure sterilization modifies acellular lung mechanics, with potential implications for lung bioengineering. Keywords: Gamma irradiation , Lung bioengineering , Lung decellularization , Organ scaffold , Pulmonary mechanics , Decellularization , Gamma irradiation , Mouse lung , Pulmonary mechanics , dodecyl sulfate sodium , animal tissue , Article , artificial ventilation , bioengineering , bioreactor , compliance physical , controlled study , freezing , gamma irradiation , lung , lung mechanics , lung resistance , male , mouse , nonhuman , room temperature , scanning electron microscopy , tissue scaffold , trachea pressure.
Nonaka, P. Lung bioengineering based on decellularized organ scaffolds is a potential alternative for transplantation. The resistance RL and elastance EL of the decellularized lungs were computed by linear regression fitting of the recorded signals tracheal pressure, flow, and volume during mechanical ventilation.
RL was not significantly modified by freezing-thawing: from 0. EL slightly increased from Sanzana, E. Role of porosity and pore architecture in the in vivo bone regeneration capacity of biodegradable glass scaffolds Journal of Biomedical Materials Research - Part A , , 6 , The aim of this work is to shed light on the role of porosity and pore architecture in the in vivo bone regeneration capacity of biodegradable glass scaffolds. A calcium phosphate glass in the system P2O5-CaO-Na2O-TiO2 was foamed using two different porogens, namely albumen and hydrogen peroxide H2O2 ; the resulting three-dimensional porous structures were characterized and implanted in New Zealand rabbits to study their in vivo behavior.
After 12 weeks of implantation, histology results revealed a good osteointegration for both types of scaffolds. The quantitative morphometric analysis showed the substitution of the biomaterial by new bone in the case of glasses foamed with albumen.
In contrast, bone neoformation and material resorption were significantly lower in the defects filled with the scaffolds foamed with H2O2. The results obtained in this study showed that both calcium phosphate glass scaffolds were osteoconductive, biocompatible, and biodegradable materials. However, differences in porosity, pore architecture, and microstructure led to substantially different in vivo response. Keywords: Bone substitutes , Calcium phosphate glasses , in vivo , Scaffolds , Tissue engineering.
Le Roux, D. Louw, A. Novel S-adenosyl-L-methionine decarboxylase inhibitors as potent antiproliferative agents against intraerythrocytic Plasmodium falciparum parasites International Journal for Parasitology: Drugs and Drug Resistance , 4, 1 , S-adenosyl-l-methionine decarboxylase AdoMetDC in the polyamine biosynthesis pathway has been identified as a suitable drug target in Plasmodium falciparum parasites, which causes the most lethal form of malaria.
The in vitro efficacy of Genz was markedly increased by nanoencapsulation in immunoliposomes, which specifically targeted intraerythrocytic P. Keywords: Immunoliposomes , Plasmodium , Polyamines , S-adenosyl-l-methionine decarboxylase.
Fiz, J. The consequences of phrenic nerve paralysis vary from a considerable reduction in respiratory function to an apparently normal state. Acoustic analysis of lung sound intensity LSI could be an indirect non-invasive measurement of respiratory muscle function, comparing activity on the two sides of the thoracic cage. Subjects were in sitting position and two acoustic sensors were placed on their back, on the left and right sides.
LSI was determined from 1. LSI was significantly greater on the normal In the healthy subjects, the LSI was similar on both left Furthermore, the LSI from the affected side of patients was close to the background noise level, at low airflows. As the airflow increases, the LSI from the affected side did also increase, but never reached the levels seen in healthy subjects. The acoustic analysis of LSI is a relevant non-invasive technique to assess respiratory function.
This method could reinforce the reliability of the diagnosis of unilateral phrenic paralysis, as well as the monitoring of these patients. Evidence towards improved estimation of respiratory muscle effort from diaphragm mechanomyographic signals with cardiac vibration interference using sample entropy with fixed tolerance values PLoS ONE 9, 2 , e The analysis of amplitude parameters of the diaphragm mechanomyographic MMGdi signal is a non-invasive technique to assess respiratory muscle effort and to detect and quantify the severity of respiratory muscle weakness.
The amplitude of the MMGdi signal is usually evaluated using the average rectified value or the root mean square of the signal. However, these estimations are greatly affected by the presence of cardiac vibration or mechanocardiographic MCG noise. In this study, we present a method for improving the estimation of the respiratory muscle effort from MMGdi signals that is robust to the presence of MCG. This method is based on the calculation of the sample entropy using fixed tolerance values fSampEn , that is, with tolerance values that are not normalized by the local standard deviation of the window analyzed.
The behavior of the fSampEn parameter was tested in synthesized mechanomyographic signals, with different ratios between the amplitude of the MCG and clean mechanomyographic components. As an example of application of this technique, the use of fSampEn was explored also in recorded MMGdi signals, with different inspiratory loads.
The results with both synthetic and recorded signals indicate that the entropy parameter is less affected by the MCG noise, especially at low signal-to-noise ratios. Therefore, we believe that the proposed fSampEn parameter could improve estimates of respiratory muscle effort from MMGdi signals with the presence of MCG interference. Understanding odor information segregation in the olfactory bulb by means of mitral and tufted cells PLoS ONE 9, 10 , e Odor identification is one of the main tasks of the olfactory system.
It is performed almost independently from the concentration of the odor providing a robust recognition. This capacity to ignore concentration information does not preclude the olfactory system from estimating concentration itself. Significant experimental evidence has indicated that the olfactory system is able to infer simultaneously odor identity and intensity. However, it is still unclear at what level or levels of the olfactory pathway this segregation of information occurs. In this work, we study whether this odor information segregation is performed at the input stage of the olfactory bulb: the glomerular layer.
To this end, we built a detailed neural model of the glomerular layer based on its known anatomical connections and conducted two simulated odor experiments. In the first experiment, the model was exposed to an odor stimulus dataset composed of six different odorants, each one dosed at six different concentrations. In the second experiment, we conducted an odor morphing experiment where a sequence of binary mixtures going from one odor to another through intermediate mixtures was presented to the model.
The results of the experiments were visualized using principal components analysis and analyzed with hierarchical clustering to unveil the structure of the high-dimensional output space. Additionally, Fisher's discriminant ratio and Pearson's correlation coefficient were used to quantify odor identity and odor concentration information respectively. Our results showed that the architecture of the glomerular layer was able to mediate the segregation of odor information obtaining output spiking sequences of the principal neurons, namely the mitral and external tufted cells, strongly correlated with odor identity and concentration, respectively.
An important conclusion is also that the morphological difference between the principal neurons is not key to achieve odor information segregation. Rajzer, I. NHOst cell culture studies showed that higher alkaline phosphatase ALP activity and better mineralization were obtained in the case of composite materials than in pure PCL scaffolds.
Keywords: Bilayer fibrous scaffold , Ceramic nanoparticles , Electrospinning , Gelatin , Polycaprolactone , Biomechanics , Bone , Calcium phosphate , Cell culture , Electrospinning , Fourier transform infrared spectroscopy , Mechanical properties , Mineralogy , Nanoparticles , Phosphatases , Polycaprolactone , Scanning electron microscopy , X ray diffraction , Polycaprolactone , Alkaline phosphatase activity , Bone tissue engineering , Calcium phosphate nanoparticles , Ceramic nanoparticles , Fibrous scaffolds , Gelatin , Simulated body fluids , Wide-angle x-ray diffraction , Electrospuns , Scaffolds biology , Electrospinning.
Serra, T. Achieving high quality 3D-printed structures requires establishing the right printing conditions. Finding processing conditions that satisfy both the fabrication process and the final required scaffold properties is crucial. This work stresses the importance of studying the outcome of the plasticizing effect of PEG on PLA-based blends used for the fabrication of 3D-direct-printed scaffolds for tissue engineering applications. Surface analysis and differential scanning calorimetry revealed a rearrangement of polymer chains and a topography, wettability and elastic modulus increase of the studied surfaces as PEG was incorporated.
In vitro degradation studies showed that the inclusion of PEG significantly accelerated the degradation rate of the material. Results indicated that the presence of PEG not only improves PLA processing but also leads to relevant surface, geometrical and structural changes including modulation of the degradation rate of PLA-based 3D printed scaffolds.
Dietrich, M. Paralogs of holE are also present on many conjugative plasmids and on phage P1 hot gene. Microarray studies comparing the transcriptional profiles of Escherichia coli holE, hha, and ydgT mutants revealed highly similar expression patterns for strains harboring holE and ydgT alleles. Among the genes differentially regulated in both mutants were genes of the tryptophanase tna operon. The tna operon consists of a transcribed leader region, tnaL, and two structural genes, tnaA and tnaB.
Further experiments with transcriptional lacZ fusions tnaL::lacZ and tnaA::lacZ indicate that HolE and YdgT downregulate expression of the tna operon by possibly increasing the level of Rho-dependent transcription termination at the tna operon's leader region. Thus, for the first time, a regulatory function can be attributed to HolE, in addition to its role as structural component of the DNA polymerase III complex. Malandrino, A. Numerical exploration of the combined effect of nutrient supply, tissue condition and deformation in the intervertebral disc Journal of Biomechanics 47, 6 , Novel strategies to heal discogenic low back pain could highly benefit from comprehensive biophysical studies that consider both mechanical and biological factors involved in intervertebral disc degeneration.
A decrease in nutrient availability at the bone-disc interface has been indicated as a relevant risk factor and as a possible initiator of cell death processes. Mechanical behaviour of both healthy and degenerated discs could highly interact with cell death in these compromised situations. In the present study, a mechano-transport finite element model was used to investigate the nature of mechanical effects on cell death processes via load-induced metabolic transport variations.
Cycles of static sustained compression were chosen to simulate daily human activity. Healthy and degenerated cases were simulated as well as a reduced supply of solutes and an increase in solute exchange area at the bone-disc interface. Results showed that a reduction in metabolite concentrations at the bone-disc boundaries induced cell death, even when the increased exchange area was simulated. Slight local mechanical enhancements of glucose in the disc centre were capable of decelerating cell death but occurred only with healthy mechanical properties.
However, mechanical deformations were responsible for a worsening in terms of cell death in the inner annulus, a disadvantaged zone far from the boundary supply with both an increased cell demand and a strain-dependent decrease of diffusivity. Such adverse mechanical effects were more accentuated when degenerative properties were simulated. Overall, this study paves the way for the use of biophysical models for a more integrated understanding of intervertebral disc pathophysiology.
Keywords: Boundary conditions , Cell nutrition , Cell viability , Computational analysis , Intervertebraldisc , Softtissuebiomechanics. In the present work we characterize the YgeH protein from the enteroaggregative E. Results We show that both E. Interestingly, this is not the rule for all YgeH proteins: the YgeH protein from the enterohaemorragic E. H-NS represses ygeH expression under all growth conditions tested, and binds with specificity to the ygeH promoter region.
Conclusion E. Trepat, Xavier, A virtually universal feature of adherent cells is their ability to exert traction forces. To measure these forces, several methods have been developed over the past 15 years. They show that the cycle of cell motility is exquisitely synchronized by a cycle of traction forces. Here, I discuss some open questions that derive from the work of the authors and other laboratories as regards the relationship between cell motility and traction forces.
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