We consider inference about a scalar coefficient in a linear regression with spatially correlated errors. Recent suggestions for more robust inference require stationarity of both regressors and ...dependent variables for their large sample validity. This rules out many empirically relevant applications, such as difference-in-difference designs. We develop a robustified version of the recently suggested SCPC method that addresses this challenge. We find that the method has good size properties in a wide range of Monte Carlo designs that are calibrated to real world applications, both in a pure cross sectional setting, but also for spatially correlated panel data. We provide numerically efficient methods for computing the associated spatial-correlation robust test statistics, critical values, and confidence intervals.
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► Advancements of Al-MOF design in academic research. ► Progress in the industrial production of Al-MOFs. ► Perspectives on large-scale application of metal–organic frameworks.
...Al-based metal–organic frameworks (Al-MOFs) were first prepared and intensively studied by Férey and co-workers. They synthesized and characterized various new structures (e.g. MIL-53, MIL-96, MIL-100, MIL-110). In parallel, BASF SE developed an own portfolio of MOFs. The synthesis for one of these Al-MOFs (Basolite A520) has recently been optimized to allow for organic solvent-free preparation. Basolite A520 can now be synthesized in a water-based route that has already led to ton-scale production. Thereby the Al-MOF is industrially produced via both an economic and environmentally compatible process. This reliable access together with their adsorption properties paves the way to the broad application of MOFs. The latter is driven by the current global megatrends that require innovative applications by high potential materials.
Mechanotransduction, the transformation of mechanical force into an electrical signal, allows living organisms to hear, register movement and gravity, detect touch, and sense changes in cell volume ...and shape. Hair cells in the inner ear are specialized mechanoreceptor cells that detect sound and head movement. The mechanotransduction machinery of hair cells is extraordinarily sensitive and responds to minute physical displacements on a submillisecond timescale. The recent discovery of several molecular constituents of the mechanotransduction machinery of hair cells provides a new framework for the interpretation of biophysical data and necessitates revision of prevailing models of mechanotransduction.
Abstract
Aims
We examined prevalence and progression of retinopathy in dependence on diabetes duration in order to estimate the probability of progression.
Patients/Methods
In a retrospective ...cohort-analysis from an academic outpatient department of endocrinology and metabolic diseases we analyzed 17461 consultations of 4513 patients with DM2 from 1987 to 2014. 50.3% of the patients (n=2272) had at least one documented result of funduscopy.
Results
25.8% of the patients had retinopathy (20.2% non-proliferative, 4.7% proliferative, 0.7% were not classified, 0.1% blindness). The prevalence of retinopathy in dependence on diabetes duration was 1.1% at diagnosis, 6.6% after 0<5 years, 12% after 5<10 years, 24% after 10<15 years, 39.9% after 15<20 years, 52.7% after 20<25 years, 58.7% after 25<30 years and 63% after ≥30 years. In a subset of 586 (25.7%) patients with retinal photography of 3 consecutive years 7.0% showed deterioration after one and 12.2% after two years; 2.6% improved after one and 2.8% after two years. 201 (34.3%) of this group had<10 years diabetes and lower deterioration (4.5% worsened after one and 9.5% after two years). Their retinopathy mainly transformed from no retinopathy to non-proliferative. Four patients (2.0%) developed proliferative retinopathy.
Conclusions/Interpretations
Within the first 10 years of diabetes duration, the prevalence of retinopathy is low and the progression infrequent. Most patients have a non-proliferative form which can be reversible and rarely requires interventions. Patients with DM2 without retinopathy and good glycaemic control do not run into additional risk from expanding funduscopy intervals to biennial.
Autosomal recessive and autosomal dominant polycystic kidney disease (ARPKD, ADPKD) are systemic disorders with pronounced hepatorenal phenotypes. While the main underlying genetic causes of both ...ARPKD and ADPKD have been well-known for years, the exact molecular mechanisms resulting in the observed clinical phenotypes in the different organs, remain incompletely understood. Recent research has identified cellular metabolic changes in PKD. These findings are of major relevance as there may be an immediate translation into clinical trials and potentially clinical practice. Here, we review important results in the field regarding metabolic changes in PKD and their modulation as a potential target of systemic treatment.
It is well known that, in misspecified parametric models, the maximum likelihood estimator (MLE) is consistent for the pseudo-true value and has an asymptotically normal sampling distribution with ..."sandwich" covariance matrix. Also, posteriors are asymptotically centered at the MLE, normal, and of asymptotic variance that is, in general, different than the sandwich matrix. It is shown that due to this discrepancy, Bayesian inference about the pseudo-true parameter value is, in general, of lower asymptotic frequentist risk when the original posterior is substituted by an artificial normal posterior centered at the MLE with sandwich covariance matrix. An algorithm is suggested that allows the implementation of this artificial posterior also in models with high dimensional nuisance parameters which cannot reasonably be estimated by maximizing the likelihood.
Development of sustainable routes for synthesis of zeolites is very important because of wide applications of zeolites at large scale in the fields of catalysis, adsorption, and separation. Here we ...report a novel and generalized route for synthesis of zeolites in the presence of NH4F from grinding the anhydrous starting solid materials and heating at 140–240 °C. Accordingly, zeolites of MFI, BEA*, EUO, and TON structures have been successfully synthesized. The presence of F– drives the crystallization of these zeolites from amorphous phase. Compared with conventional hydrothermal synthesis, the synthesis in this work not only simplifies the synthesis process but also significantly enhances the zeolite yields. These features should be potentially of great importance for industrial production of zeolites at large scale in the future.
Significance Cochlear hair cells are sensory receptors of the inner ear that detect sound via opening of mechanically sensitive transduction channels at the tips of the eponymous hairs. The ...conductance of the channel increases two-fold along the cochlea, but neither its molecular structure nor mechanism of tonotopic variation is known. We show that when either of two deafness-linked proteins, transmembrane channel-like protein isoform 1 (TMC1) and tetraspan membrane protein of hair cell stereocilia (TMHS, also known as lipoma HMGIC fusion partner-like 5, LHFPL5) is knocked out, the conductance variation is lost. Furthermore, the effect of LHFPL5 is attributable to down-regulation of TMC1, suggesting that titrating the TMC1 content of the channel modulates its conductance. Evidence indicates that both proteins interact with the mechanotransduction channel and also with protocadherin-15, a component of the extracellular tip link that applies force to the channel.
Cochlear hair cells convert sound stimuli into electrical signals by gating of mechanically sensitive ion channels in their stereociliary (hair) bundle. The molecular identity of this ion channel is still unclear, but its properties are modulated by accessory proteins. Two such proteins are transmembrane channel-like protein isoform 1 (TMC1) and tetraspan membrane protein of hair cell stereocilia (TMHS, also known as lipoma HMGIC fusion partner-like 5, LHFPL5), both thought to be integral components of the mechanotransduction machinery. Here we show that, in mice harboring an Lhfpl5 null mutation, the unitary conductance of outer hair cell mechanotransducer (MT) channels was reduced relative to wild type, and the tonotopic gradient in conductance, where channels from the cochlear base are nearly twice as conducting as those at the apex, was almost absent. The macroscopic MT current in these mutants was attenuated and the tonotopic gradient in amplitude was also lost, although the current was not completely extinguished. The consequences of Lhfpl5 mutation mirror those due to Tmc1 mutation, suggesting a part of the MT-channel conferring a large and tonotopically variable conductance is similarly disrupted in the absence of Lhfpl5 or Tmc1 . Immunolabelling demonstrated TMC1 throughout the stereociliary bundles in wild type but not in Lhfpl5 mutants, implying the channel effect of Lhfpl5 mutations stems from down-regulation of TMC1. Both LHFPL5 and TMC1 were shown to interact with protocadherin-15, a component of the tip link, which applies force to the MT channel. We propose that titration of the TMC1 content of the MT channel sets the gradient in unitary conductance along the cochlea.
Primary cilia project from the surface of most vertebrate cells and are key in sensing extracellular signals and locally transducing this information into a cellular response. Recent findings show ...that primary cilia are not merely static organelles with a distinct lipid and protein composition. Instead, the function of primary cilia relies on the dynamic composition of molecules within the cilium, the context‐dependent sensing and processing of extracellular stimuli, and cycles of assembly and disassembly in a cell‐ and tissue‐specific manner. Thereby, primary cilia dynamically integrate different cellular inputs and control cell fate and function during tissue development. Here, we review the recently emerging concept of primary cilia dynamics in tissue development, organization, remodeling, and function.
This review summarizes recent insights into the dynamic changes in primary cilia composition, signaling, and assembly and disassembly during tissue organization.
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