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911.
Background: Self-sustained oscillations are a ubiquitous and vital phenomenon in living systems. From primitive single-cellular bacteria to the most sophisticated organisms, periodicities have been observed in a broad spectrum of biological processes such as neuron firing, heart beats, cell cycles, circadian rhythms, etc. Defects in these oscillators can cause diseases from insomnia to cancer. Elucidating their fundamental mechanisms is of great significance to diseases, and yet challenging, due to the complexity and diversity of these oscillators. Results: Approaches in quantitative systems biology and synthetic biology have been most effective by simplifying the systems to contain only the most essential regulators. Here, we will review major progress that has been made in understanding biological oscillators using these approaches. The quantitative systems biology approach allows for identification of the essential components of an oscillator in an endogenous system. The synthetic biology approach makes use of the knowledge to design the simplest, de novo oscillators in both live cells and cell-free systems. These synthetic oscillators are tractable to further detailed analysis and manipulations. Conclusion: With the recent development of biological and computational tools, both approaches have made significant achievements.  相似文献   
912.
Discovery of new protease inhibitors may result in potential therapeutic agents or useful biotechnological tools. Obtainment of these molecules from natural sources requires simple, economic, and highly efficient purification protocols. The aim of this work was the obtainment of affinity matrices by the covalent immobilization of dipeptidyl peptidase IV (DPP-IV) and papain onto cellulose membranes, previously activated with formyl (FCM) or glyoxyl groups (GCM). GCM showed the highest activation grade (10.2?µmol aldehyde/cm2). We implemented our strategy for the rational design of immobilized derivatives (RDID) to optimize the immobilization. pH 9.0 was the optimum for the immobilization through the terminal α-NH2, configuration predicted as catalytically competent. However, our data suggest that protein immobilization may occur via clusters of few reactive groups. DPP-IV?GCM showed the highest maximal immobilized protein load (2.1?µg/cm2), immobilization percentage (91%), and probability of multipoint covalent attachment. The four enzyme-support systems were able to bind at least 80% of the reversible competitive inhibitors bacitracin/cystatin, compared with the available active sites in the immobilized derivatives. Our results show the potentialities of the synthesized matrices for affinity purification of protease inhibitors and confirm the robustness of the RDID strategy to optimize protein immobilization processes with further practical applications.  相似文献   
913.
Endoglucanase production by Aspergillus oryzae ATCC 10124 cultivated in rice husks or peanut shells was optimized by experimental design as a function of humidity, time, and temperature. The optimum temperature for the endoglucanase activity was estimated by a univariate analysis (one factor at the time) as 50°C (rice husks) and 60°C (peanut shells), however, by a multivariate analysis (synergism of factors), it was determined a different temperature (56°C) for endoglucanase from peanut shells. For the optimum pH, values determined by univariate and multivariate analysis were 5 and 5.2 (rice husk) and 5 and 7.6 (peanut shells). In addition, the best half-lives were observed at 50°C as 22.8?hr (rice husks) and 7.3?hr (peanut shells), also, 80% of residual activities was obtained between 30 and 50°C for both substrates, and the pH stability was improved at 5–7 (rice hulls) and 6–9 (peanut shells). Both endoglucanases obtained presented different characteristics as a result of the versatility of fungi in different substrates.  相似文献   
914.
Protein phosphatase‐1 and phosphatase‐2A are two ubiquitously expressed enzymes known to catalyze the majority of dephosphorylation reactions on serine and threonine inside cells. They play roles in most cellular processes and are tightly regulated by regulatory subunits in holoenzymes. Their misregulation and malfunction contribute to disease development and progression, such as in cancer, diabetes, viral infections, and neurological as well as heart diseases. Therefore, targeting these phosphatases for therapeutic use would be highly desirable; however, their complex regulation and high conservation of the active site have been major hurdles for selectively targeting them in the past. In the last decade, new approaches have been developed to overcome these hurdles and have strongly revived the field. I will focus here on peptide‐based approaches, which contributed to showing that these phosphatases can be targeted selectively and aided in rethinking the design of selective phosphatase modulators. Finally, I will give a perspective on www.depod.org , the human dephosphorylation database, and how it can aid phosphatase modulator design. © 2017 The Authors. Journal of Peptide Science published by European Peptide Society and John Wiley & Sons Ltd.  相似文献   
915.
The life cycle environmental profile of energy‐consuming products, such as air conditioning, is dominated by the products’ use phase. Different user behavior patterns can therefore yield large differences in the results of a cradle‐to‐grave assessment. Although this variation and uncertainty is increasingly recognized, it remains often poorly characterized in life cycle assessment (LCA) studies. Today, pervasive sensing presents the opportunity to collect rich data sets and improve profiling of use‐phase parameters, in turn facilitating quantification and reduction of this uncertainty in LCA. This study examined the case of energy use in building cooling systems, focusing on global warming potential (GWP) as the impact category. In Singapore, building cooling systems or air conditioning consumes up to 37% of national electricity demand. Lack of consideration of variation in use‐phase interaction leads to the oversized designs, wasted energy, and therefore reducible GWP. Using a high‐resolution data set derived from sensor observations, energy use and behavior patterns of single‐office occupants were characterized by probabilistic distributions. The interindividual variability and use‐phase variables were propagated in a stochastic model for the life cycle of air‐conditioning systems and simulated by way of Monte Carlo analysis. Analysis of the generated uncertainties identified plausible reductions in global warming impact through modifying user interaction. Designers concerned about the environmental profile of their products or systems need better representation of the underlying variability in use‐phase data to evaluate the impact. This study suggests that data can be reliably provided and incorporated into the life cycle by proliferation of pervasive sensing, which can only continue to benefit future LCA.  相似文献   
916.
Spinal cages are used to create a suitable mechanical environment for interbody fusion in cases of degenerative spinal instability. Due to individual variations in bone structures and pathological conditions, patient-specific cages can provide optimal biomechanical conditions for fusion, strengthening patient recovery. Finite element analysis (FEA) is a valuable tool in the biomechanical evaluation of patient-specific cage designs, but the time- and labor-intensive process of modeling limits its clinical application. In an effort to facilitate the design and analysis of patient-specific spinal cages, an integrated CAD–FEA system (CASCaDeS, comprehensive analytical spinal cage design system) was developed. This system produces a biomechanical-based patient-specific design of spinal cages and is capable of rapid implementation of finite element modeling. By comparison with commercial software, this system was validated and proven to be both accurate and efficient. CASCaDeS can be used to design patient-specific cages with a superior biomechanical performance to commercial spinal cages.  相似文献   
917.
Antimicrobial peptides (AMPs), as evolutionarily conserved components of innate immune system, protect against pathogens including bacteria, fungi, viruses, and parasites. In general, AMPs are relatively small peptides (<10 kDa) with cationic nature and amphipathic structure and have modes of action different from traditional antibiotics. Up to now, there are more than 19 000 AMPs that have been reported, including those isolated from nature sources or by synthesis. They have been considered to be promising substitutes of conventional antibiotics in the quest to address the increasing occurrence of antibiotic resistance. However, most AMPs have modest direct antimicrobial activity, and their mechanisms of action, as well as their structure–activity relationships, are still poorly understood. Computational strategies are invaluable assets to provide insight into the activity of AMPs and thus exploit their potential as a new generation of antimicrobials. This article reviews the advances of AMP databases and computational tools for the prediction and design of new active AMPs. Copyright © 2016 European Peptide Society and John Wiley & Sons, Ltd.  相似文献   
918.
Restoring degraded Australian landscapes through revegetation is a key concern of land holders, NGOs and government agencies. With the advent of climate change, it is increasingly important that revegetation activities take into consideration the species and provenance of plant materials to ensure that environmental plantings will be resilient to future climate conditions. A major strength of the past 30 years restoration programmes is the development of a distributed network of educated and experienced practitioners. We have recently invited stakeholders from among this network to participate in a process to cost‐effectively build Environmental Research Infrastructure – a nationally distributed network of restoration plantings that explore a broad range of research activities including a better understanding of the adaptive responses of different species and provenances. This would also facilitate long‐term monitoring of change and adaptation across Australia, providing a wealth of information to inform future conservation and restoration programmes.  相似文献   
919.
Imagery collected from Autonomous Underwater Vehicles (AUVs) provides a novel means of monitoring changes in benthic ecosystems over large spatial scales and depth ranges. However, for many benthic ecosystems there is little baseline data to quantify temporal and spatial variance for key indicator species. This information is crucial for isolating background “noise” from long-term “signals”. Here we quantify components of variance for five key deep-water sessile invertebrate species across four long-term benthic monitoring sites in a region undergoing strong climate-driven changes. We use linear mixed models to estimate the contribution of sources of spatial and temporal variance in species covers from empirical data. We then combine this information with projected long-term climate-driven changes in the cover of these groups and test the power of various survey designs to detect change through time. Large short-term temporal and spatial variability in the cover of a gorgonian octocoral results in high components of variance that limit the detectability of the projected long-term trend for this species. Conversely, for three of the sponge species high power is achievable with revisits to the four original sites every two years until 2060. By including more sites in the revisit design, high power can be achieved with less frequent revisits. For the fifth species, we find high power is unachievable due to the small trend predicted. Overall, we highlight how examination of components of variance in a system can aid in the selection of suitable indicators and the establishment of effective monitoring programs.  相似文献   
920.
A total of 11 pyrazinamide derivatives were designed and synthesised using pyrazinamide as the lead compound, which was optimised by structural modification with alkyl chains, six-membered rings, and bioisosterism, respectively. The target compounds were synthesised using pyrazinecarboxylic acid as the starting material by acylation, amidation, and alkylation, respectively. Their structures were confirmed by 1H NMR, 13C NMR, HRESIMS, and elemental analysis, respectively. The bioactivities of derivatives were assayed using bacteriostatic experiment and minimum inhibitory concentration experiment. It was showed that the derivatives had good inhibitory effect on Mycobacterium tuberculosis. The biological activity of derivative 1f was the best among all compounds, its antibacterial activity was 99.6%, and the minimum inhibitory concentration was 8.0?µg/mL.  相似文献   
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