Metal–organic frameworks (MOFs) are constructed by linking inorganic units with organic linkers to make extended networks. Though more than 20 000 MOF structures have been reported most of these are ...ordered and largely composed of a limited number of different kinds building units, and very few have multiple different building units (heterogeneous). Although heterogeneity and multiplicity is a fundamental characteristic of biological systems, very few synthetic materials incorporate heterogeneity without losing crystalline order. Thus, the question arises: how do we introduce heterogeneity into MOFs without losing their ordered structure? This Review outlines strategies for varying the building units within both the backbone of the MOF and its pores to produce the heterogeneity that is sought after. The impact this heterogeneity imparts on the properties of a MOF is highlighted. We also provide an update on the MOF industry as part of this themed issue for the 150th anniversary of BASF.
Mix and MOF: Most metal–organic frameworks (MOFs) are ordered and generally composed of only a few of repeating building unit. This Review is describes how the use of various different components in the MOF backbone and within the pores of the MOF can produce heterogeneity without losing the order (crystallinity) of the MOF structure.
Long Non-Coding RNAs in Kidney Disease Ignarski, Michael; Islam, Rashidul; Müller, Roman-Ulrich
International journal of molecular sciences,
07/2019, Letnik:
20, Številka:
13
Journal Article
Recenzirano
Odprti dostop
Non-coding RNA species contribute more than 90% of all transcripts and have gained increasing attention in the last decade. One of the most recent members of this group are long non-coding RNAs ...(lncRNAs) which are characterized by a length of more than 200 nucleotides and a lack of coding potential. However, in contrast to this simple definition, lncRNAs are heterogenous regarding their molecular function-including the modulation of small RNA and protein function, guidance of epigenetic modifications and a role as enhancer RNAs. Furthermore, they show a highly tissue-specific expression pattern. These aspects already point towards an important role in cellular biology and imply lncRNAs as players in development, health and disease. This view has been confirmed by numerous publications from different fields in the last years and has raised the question as to whether lncRNAs may be future therapeutic targets in human disease. Here, we provide a concise overview of the current knowledge on lncRNAs in both glomerular and tubulointerstitial kidney disease.
Abstract
The social cost of carbon dioxide (SC-CO
2
) measures the monetized value of the damages to society caused by an incremental metric tonne of CO
2
emissions and is a key metric informing ...climate policy. Used by governments and other decision-makers in benefit–cost analysis for over a decade, SC-CO
2
estimates draw on climate science, economics, demography and other disciplines. However, a 2017 report by the US National Academies of Sciences, Engineering, and Medicine
1
(NASEM) highlighted that current SC-CO
2
estimates no longer reflect the latest research. The report provided a series of recommendations for improving the scientific basis, transparency and uncertainty characterization of SC-CO
2
estimates. Here we show that improved probabilistic socioeconomic projections, climate models, damage functions, and discounting methods that collectively reflect theoretically consistent valuation of risk, substantially increase estimates of the SC-CO
2
. Our preferred mean SC-CO
2
estimate is $185 per tonne of CO
2
($44–$413 per tCO
2
: 5%–95% range, 2020 US dollars) at a near-term risk-free discount rate of 2%, a value 3.6 times higher than the US government’s current value of $51 per tCO
2
. Our estimates incorporate updated scientific understanding throughout all components of SC-CO
2
estimation in the new open-source Greenhouse Gas Impact Value Estimator (GIVE) model, in a manner fully responsive to the near-term NASEM recommendations. Our higher SC-CO
2
values, compared with estimates currently used in policy evaluation, substantially increase the estimated benefits of greenhouse gas mitigation and thereby increase the expected net benefits of more stringent climate policies.
This paper considers nonstandard hypothesis testing problems that involve a nuisance parameter. We establish an upper bound on the weighted average power of all valid tests, and develop a numerical ...algorithm that determines a feasible test with power close to the bound. The approach is illustrated in six applications: inference about a linear regression coefficient when the sign of a control coefficient is known; small sample inference about the difference in means from two independent Gaussian samples from populations with potentially different variances; inference about the break date in structural break models with moderate break magnitude; predictability tests when the regressor is highly persistent; inference about an interval identified parameter; and inference about a linear regression coefficient when the necessity of a control is in doubt.
The term SCA refers to a phenotypically and genetically heterogeneous group of autosomal dominant spinocerebellar ataxias. Phenotypically they present as gait ataxia frequently in combination with ...dysarthria and oculomotor problems. Additional signs and symptoms are common and can include various pyramidal and extrapyramidal signs and intellectual impairment. Genetic causes of SCAs are either repeat expansions within disease genes or common mutations (point mutations, deletions, insertions etc.). Frequently the two types of mutations cause indistinguishable phenotypes (locus heterogeneity). This article focuses on SCAs caused by common mutations. It describes phenotype and genotype of the presently 27 types known and discusses the molecular pathogenesis in those 21 types where the disease gene has been identified. Apart from the dominant types, the article also summarizes findings in a variant caused by mutations in a mitochondrial gene. Possible common disease mechanisms are considered based on findings in the various SCAs described.
It is generally accepted that the hydrophilic property of graphene can be affected by the underlying substrate. However, the role of intrinsic vs substrate contributions and the related mechanisms ...are vividly debated. Here, we show that the intrinsic hydrophilicity of graphene can be intimately connected to the position of its Fermi level, which affects the interaction between graphene and water molecules. The underlying substrate, or dopants, can tune hydrophilicity by modulating the Fermi level of graphene. By shifting the Fermi level of graphene away from its Dirac point, via either chemical or electrical voltage doping, we show enhanced hydrophilicity with experiments and first principle simulations. Increased vapor condensation on graphene, induced by a simple shifting of its Fermi level, exemplifies applications in the area of interfacial transport phenomena.
We propose a method for constructing confidence intervals that account for many forms of spatial correlation. The interval has the familiar “estimator plus and minus a standard error times a critical ...value” form, but we propose new methods for constructing the standard error and the critical value. The standard error is constructed using population principal components from a given “worst‐case” spatial correlation model. The critical value is chosen to ensure coverage in a benchmark parametric model for the spatial correlations. The method is shown to control coverage in finite sample Gaussian settings in a restricted but nonparametric class of models and in large samples whenever the spatial correlation is weak, that is, with average pairwise correlations that vanish as the sample size gets large. We also provide results on the efficiency of the method.
Hair cells in the inner ear convert mechanical stimuli provided by sound waves and head movements into electrical signal. Several mechanically evoked ionic currents with different properties have ...been recorded in hair cells. The search for the proteins that form the underlying ion channels is still in progress. The mechanoelectrical transduction (MET) channel near the tips of stereociliary in hair cells, which is responsible for sensory transduction, has been studied most extensively. Several components of the sensory mechanotransduction machinery in stereocilia have been identified, including the multi-transmembrane proteins tetraspan membrane protein in hair cell stereocilia (TMHS)/LHFPL5, transmembrane inner ear (TMIE) and transmembrane channel-like proteins 1 and 2 (TMC1/2). However, there remains considerable uncertainty regarding the molecules that form the channel pore. In addition to the sensory MET channel, hair cells express the mechanically gated ion channel PIEZO2, which is localized near the base of stereocilia and not essential for sensory transduction. The function of PIEZO2 in hair cells is not entirely clear but it might have a role in damage sensing and repair processes. Additional stretch-activated channels of unknown molecular identity and function have been found to localize at the basolateral membrane of hair cells. Here, we review current knowledge regarding the different mechanically gated ion channels in hair cells and discuss open questions concerning their molecular composition and function.
Molecular evolution can be conceptualized as a walk over a “fitness landscape”, or the function of fitness (e.g., catalytic activity) over the space of all possible sequences. Understanding evolution ...requires knowing the structure of the fitness landscape and identifying the viable evolutionary pathways through the landscape. However, the fitness landscape for any catalytic biomolecule is largely unknown. The evolution of catalytic RNA is of special interest because RNA is believed to have been foundational to early life. In particular, an essential activity leading to the genetic code would be the reaction of ribozymes with activated amino acids, such as 5(4H)-oxazolones, to form aminoacyl-RNA. Here we combine in vitro selection with a massively parallel kinetic assay to map a fitness landscape for self-aminoacylating RNA, with nearly complete coverage of sequence space in a central 21-nucleotide region. The method (SCAPE: sequencing to measure catalytic activity paired with in vitro evolution) shows that the landscape contains three major ribozyme families (landscape peaks). An analysis of evolutionary pathways shows that, while local optimization within a ribozyme family would be possible, optimization of activity over the entire landscape would be frustrated by large valleys of low activity. The sequence motifs associated with each peak represent different solutions to the problem of catalysis, so the inability to traverse the landscape globally corresponds to an inability to restructure the ribozyme without losing activity. The frustrated nature of the evolutionary network suggests that chance emergence of a ribozyme motif would be more important than optimization by natural selection.
PDF
