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51.
Metagenomic sequencing data provide a rich resource from which to expand our understanding of differential protein functions involved in human health. Here, we outline a pipeline that combines microbial whole genome sequencing with protein structure data to yield a structural metagenomics-informed atlas of microbial enzyme families of interest. Visualizing metagenomics data through a structural lens facilitates downstream studies including targeted inhibition and probe-based proteomics to define at the molecular level how different enzyme orthologs impact in vivo function. Application of this pipeline to gut microbial enzymes like glucuronidases, TMA lyases, and bile salt hydrolases is expected to pinpoint their involvement in health and disease and may aid in the development of therapeutics that target specific enzymes within the microbiome. 相似文献
52.
Concrete pavements are a vital part of the transportation infrastructure, comprising nearly 25% of the interstate network in the United States. With transportation authorities and industry organizations increasingly seeking out methods to reduce their carbon footprint, there is a need to identify and quantitatively evaluate the greenhouse gas (GHG) emission reduction opportunities that exist in the concrete pavement life cycle. A select few of these opportunities are explored in this article in order to represent possible reduction approaches and their associated cost‐effectiveness: reducing embodied emissions by increasing fly ash content and by avoiding overdesign; increasing albedo by using white aggregates; increasing carbonation by temporarily stockpiling recycled concrete aggregates; and reducing vehicle fuel consumption by adding an extra rehabilitation. These reduction strategies are evaluated for interstate, arterial, collector, and local road designs under urban and rural scenarios. The results indicate that significant GHG emission reductions are possible, with over half of the scenarios resulting in 10% reductions, compared to unimproved baseline designs. Given the right conditions, each scenario has the potential to reduce GHG emissions at costs comparable to the current price of carbon. 相似文献
53.
《Bioorganic & medicinal chemistry》2020,28(1):115174
The recent renewed interest in phenotypic drug discovery has concomitantly put a focus on target deconvolution in order to achieve drug-target identification. Even though there are prescribed therapies whose mode of action is not fully understood, knowledge of the primary target will inevitably facilitate the discovery and translation of efficacy from bench to bedside. Elucidating targets and subsequent pathways engaged will also facilitate safety studies and overall development of novel drug candidates. Today, there are several techniques available for identifying the primary target, many of which rely on mass spectrometry (MS) to identify compound – target protein interactions. The Cellular Thermal Shift Assay (CETSA®) is well suited for identifying target engagement between ligands and their protein targets. Several studies have shown that CETSA combined with MS is a powerful technique that allows unlabeled target deconvolution in complex samples such as intact cells and tissues in addition to cell lysates and other protein suspensions. The applicability of CETSA MS for target deconvolution purposes will be discussed and exemplified in this mini review. 相似文献
54.
David Hunkeler 《The International Journal of Life Cycle Assessment》2006,11(6):371-382
Background, Aim and Scope
Societal assessment is advocated as one of the three pillars in the evaluation of, and movement toward, sustainability. As
is the case with the well established LCA, and the emerging LCC, societal life cycle assessment should be developed in such
as way as to permit relative product comparisons, rather than absolute analyses. The development of societal life cycle assessment
is in its infancy, and important concepts require clarification including the handling of the more than two hundred social
indicators. Therefore, any societal life cycle assessment methodology must explain why it is midpoint- or endpoint-based as
well as its reasons to be complimentary with, or included within, life cycle assessment.
Materials and Methods:
A geographically specific midpoint based societal life cycle assessment methodology, which employs labour hours as an intermediate
variable in the calculation has been developed and evaluated against an existing LCA comparing two detergents. The methodology
is based on using an existing life cycle inventory and, therefore, has identical system boundaries and functional units to
LCA. The societal life cycle assessment methodology, much like LCA, passes from inventory, through characterisation factors,
to provide an ultimate result. In analogy to economics and cost estimation, societal life cycle assessment combines, into
its statistics, both data as well as estimates, some of which are correlated to elements of the LCI. It focuses on the work
hours required to meet basic needs.A geographically specific midpoint based societal life cycle assessment methodology, which
employs labour hours as an intermediate variable in the calculation has been developed and evaluated against an existing LCA
comparing two detergents. The methodology is based on using an existing life cycle inventory and, therefore, has identical
system boundaries and functional units to LCA. The societal life cycle assessment methodology, much like LCA, passes from
inventory, through characterisation factors, to provide an ultimate result. In analogy to economics and cost estimation, societal
life cycle assessment combines, into its statistics, both data as well as estimates, some of which are correlated to elements
of the LCI. It focuses on the work hours required to meet basic needs.
Results:
The societal life cycle assessment of an appended case study indicates that Detergent 2 generates, relative Detergent 1, approximately
20% less employment in Russia, 35% less in France, and approximately five times more in Canada and South Africa, the latter
derived from its higher aluminium content. There is essentially no difference in the employment in the use country (Switzerland)
nor in Morocco, where some of the waste disposal was assumed to take place.
Discussion:
Given that housing is more affordable, in terms of shelter units per labour hour, in South Africa, compared to Europe, it
is, therefore, of no surprise that Detergent 2 provides a societal benefit in terms of housing. Detergent 2 does, however,
result in dematerialization, in that its environmental impact is lower (LCI). Therefore, as less resources are employed and
labour required, in extraction, production and transport, the societal benefits in health care, education and necessities,
a grouped variable, are lower for Detergent 2. This is despite the employment shift away from Europe and to less 'developed'
regions.
Conclusions:
The assessment of societal impacts involves several hundred specific indicators. Therefore, aggregation is, if not impossible,
at least heavily value laden and, therefore, not recommended. The impact of a societal action, derived from a product purchase
or otherwise, is also highly local. Given this, societal life cycle assessment, carried through to the midpoints, and based
on an existing LCI, has been developed as a methodology. The results, for an existing LCA-detergent case, illustrate that
societal life cycle assessment provides a means to investigate how policy and policy makers can be linked to sustainable development.
The sensitivity analyses also clarify the decisions in regards to product improvement.
Recommendations and Perspectives:
The goal of societal life cycle assessment is not to make decisions, but rather to point out tradeoffs to decision- or policy-makers.
This case, and the methodology that it is based on, permit such a comparison. Substituting Detergent 2 for Detergent 1 reduces
resource use at the expense of an increase in atmospheric and terrestrial emissions. Access to housing is improved, though
at the expense of education, health care and necessities. As a recommendation, one would look at the fact that the majority
of indicators are superior for Detergent 2 relative to Detergent 1and seek to improve the aqueous emissions in Detergent 2
via a change in the formulation. An energy or fossil fuel substitution at the site of production could also improve the societal
benefits in terms of education and health care.
While societal life cycle assessment remains in its infancy, a methodology does exist. The field can, therefore, be viewed
in a similar way to LCA in the early 1990s, with a need to validate, consolidate and, ultimately, built toward a standard.
The contribution is aimed at contributing to such a discussion and therefore proposes that a societal life cycle assessment
be LCI-derived, geographically specific, based on mid-points, and use employment as an intermediate variable. 相似文献
55.
Joshua J. Rosnow Lindsey N. Anderson Reji N. Nair Erin S. Baker 《Critical reviews in biotechnology》2017,37(5):626-640
The use of plant materials to generate renewable biofuels and other high-value chemicals is the sustainable and preferable option, but will require considerable improvements to increase the rate and efficiency of lignocellulose depolymerization. This review highlights novel and emerging technologies that are being developed and deployed to characterize the process of lignocellulose degradation. The review will also illustrate how microbial communities deconstruct and metabolize lignocellulose by identifying the necessary genes and enzyme activities along with the reaction products. These technologies include multi-omic measurements, cell sorting and isolation, nuclear magnetic resonance spectroscopy (NMR), activity-based protein profiling, and direct measurement of enzyme activity. The recalcitrant nature of lignocellulose necessitates the need to characterize the methods microbes employ to deconstruct lignocellulose to inform new strategies on how to greatly improve biofuel conversion processes. New technologies are yielding important insights into microbial functions and strategies employed to degrade lignocellulose, providing a mechanistic blueprint in order to advance biofuel production. 相似文献
56.
Ling-Wen Xu Xue-Qian Zhang Zheng Yan Zhi-Hong Li An-Jun Deng Hai-Lin Qin 《化学与生物多样性》2023,20(5):e202300230
Natural QPAs have anti-cancer property. The prodrugs of QPAs synthesized in our work with significantly improved solubility showed significantly stronger activity in animal experiments. Nevertheless, the mechanism of action of QPAs for treating cancers remains poorly understood. Here, a chemoproteomic study reveals that QPAs non-covalently and multivalently bind to PES1 in CRC cells, which impinges on the direct interaction between hTERT and hTR in the assembly of the telomerase complex, downregulates telomerase activity, and so promotes the aging process of CRC cells. This study is beneficial for us to conduct extensively the pharmaceutical chemistry research of QPAs. 相似文献
57.