Effect of Co substitution on the structural,dielectric and optical properties of KBiFe2O5

Cobalt (Co)-modified brownmillerite KBiFe2O5 (KBFO; [KBiFe2(1?x)Co2xO5 (x = 0, 0.05)]) polycrystalline is synthesized following the solid-state reaction route. Rietveld refinement of X-ray diffraction data confirmed the phase purity of KBFO and KBiFe1.9Co0.1O5 (KBFCO). The optical bandgap energy (Eg) of KBFO decreased from 1.59 to 1.51 eV because of Co substitution. The decrease in bandgap can be attributed to the tilting of the Fe–O tetrahedral structure of KBFCO. The observed room-temperature Raman peaks of KBFCO shifted by 3 cm?1 toward a lower wavenumber than that of KBFO. The shift in Raman active modes can be attributed to the change in the bond angles and bond lengths of the Fe–O tetrahedral structure and modification in response to oxygen deficiency in KBFO because of Co doping. Compared with that of KBFO, the frequency-dependent dielectric constant and dielectric loss of KBFCO decrease at room temperature, which is a con-sequence of the reduction in oxygen migration and modification in response to vibrational modes present in the sample.     

Maxwell's role in turning the concept of model into the methodology of modeling

This is a contribution towards a history and philosophy of modeling in its early stages in electromagnetism. In 1873, James Clerk Maxwell (1831–1879) hinted at the methodology of modeling at the end of his Treatise on Electricity and Magnetism. We focus on Maxwell's impact on physicists who immediately followed him, specifically Oliver Lodge (1851–1940) and George Francis FitzGerald (1851–1901). We begin with the role that the scientific concept of model played in the late nineteenth century, as assessed by Ludwig Boltzmann (1844–1906). We then discuss the role of hypothesis as a methodology, the appeal to (dynamical) illustration, and the way Maxwell applied model and working model in his studies of electromagnetism. We show that for Maxwell these key terms were kept distinct, but Lodge did not maintain these distinctions and, in this regard, FitzGerald followed Lodge. Notwithstanding Lodge's influence, Fitzgerald modified Maxwell's theory based on the mechanical model he designed, thereby implicitly taking the first step towards modeling. This methodology consists in drawing consequences from the (mechanical) model to the (electrodynamic) theory and modifying the latter in light of the functioning of the former. At the core of our argument is the thesis that it was a methodological novelty to move from the concept of model to the methodology of modeling. The introduction of modeling as a new methodology into physics in the late nineteenth century was a major event which deserves proper recognition.     

Methods for backcasting,nowcasting and forecasting using factor‐MIDAS: With an application to Korean GDP

We utilize mixed‐frequency factor‐MIDAS models for the purpose of carrying out backcasting, nowcasting, and forecasting experiments using real‐time data. We also introduce a new real‐time Korean GDP dataset, which is the focus of our experiments. The methodology that we utilize involves first estimating common latent factors (i.e., diffusion indices) from 190 monthly macroeconomic and financial series using various estimation strategies. These factors are then included, along with standard variables measured at multiple different frequencies, in various factor‐MIDAS prediction models. Our key empirical findings as follows. (i) When using real‐time data, factor‐MIDAS prediction models outperform various linear benchmark models. Interestingly, the “MSFE‐best” MIDAS models contain no autoregressive (AR) lag terms when backcasting and nowcasting. AR terms only begin to play a role in “true” forecasting contexts. (ii) Models that utilize only one or two factors are “MSFE‐best” at all forecasting horizons, but not at any backcasting and nowcasting horizons. In these latter contexts, much more heavily parametrized models with many factors are preferred. (iii) Real‐time data are crucial for forecasting Korean gross domestic product, and the use of “first available” versus “most recent” data “strongly” affects model selection and performance. (iv) Recursively estimated models are almost always “MSFE‐best,” and models estimated using autoregressive interpolation dominate those estimated using other interpolation methods. (v) Factors estimated using recursive principal component estimation methods have more predictive content than those estimated using a variety of other (more sophisticated) approaches. This result is particularly prevalent for our “MSFE‐best” factor‐MIDAS models, across virtually all forecast horizons, estimation schemes, and data vintages that are analyzed.     

Is the valid species Synchaeta monopus Plate, 1889 (Rotifera: Monogononta) a product of preparation artefacts?

The morphology of soft-bodied rotifers, including those of Synchaeta spp, can be strongly affected by preparation artefacts including contraction and deformation. The long-standing, valid species Synchaeta monopus is known exclusively from ethanol- or formaldehyde-preserved material and no live specimens of it have ever been described. Although this alone is cause for concern, we could also reproduce unique characteristics diagnostic for this species (e.g. the swollen body and the rudimental foot) by subjecting specimens of Synchaeta pectinata to the preservation conditions under which it was first described. This proxy experiment and comparisons to other Synchaeta species indicate that literature occurrences of S. monopus likely represent preserved and deformed specimens of Synchaeta cecilia or other marine species of Synchaeta, thereby highlighting the importance of thorough morphological investigations of the habitus using live specimens and of features that are unaffected by preservation (e.g. the trophi). We therefore recommend that S. monopus be listed as a species inquirenda until topotypes are examined. Furthermore, in ecological studies including rotifers, where the examination of preserved material is often unavoidable, we stress that light-microscopical images of the habitus and trophi of the specimens minimally be included to facilitate independent verification of the species assignments.     

Mechanisms regulating immune surveillance of cellular stress in cancer

The purpose of this review is to explore immune-mediated mechanisms of stress surveillance in cancer, with particular emphasis on the idea that all cancers have classical hallmarks (Hanahan and Weinberg in Cell 100:57–70, 67; Cell 144:646–674, 68) that could be interrelated. We postulate that hallmarks of cancer associated with cellular stress pathways (Luo et al. in Cell 136:823–837, 101) including oxidative stress, proteotoxic stress, mitotic stress, DNA damage, and metabolic stress could define and modulate the inflammatory component of cancer. As such, the overarching goal of this review is to define the types of cellular stress that cancer cells undergo, and then to explore mechanisms by which immune cells recognize, respond to, and are affected by each stress response.     

Intrinsically disordered proteins in crowded milieu: when chaos prevails within the cellular gumbo

Effects of macromolecular crowding on structural and functional properties of ordered proteins, their folding, interactability, and aggregation are well documented. Much less is known about how macromolecular crowding might affect structural and functional behaviour of intrinsically disordered proteins (IDPs) or intrinsically disordered protein regions (IDPRs). To fill this gap, this review represents a systematic analysis of the available literature data on the behaviour of IDPs/IDPRs in crowded environment. Although it was hypothesized that, due to the excluded-volume effects present in crowded environments, IDPs/IDPRs would invariantly fold in the presence of high concentrations of crowding agents or in the crowded cellular environment, accumulated data indicate that, based on their response to the presence of crowders, IDPs/IDPRs can be grouped into three major categories, foldable, non-foldable, and unfoldable. This is because natural cellular environment is not simply characterized by the presence of high concentration of “inert” macromolecules, but represents an active milieu, components of which are engaged in direct physical interactions and soft interactions with target proteins. Some of these interactions with cellular components can cause (local) unfolding of query proteins. In other words, since crowding can cause both folding and unfolding of an IDP or its regions, the outputs of the placing of a query protein to the crowded environment would depend on the balance between these two processes. As a result, and because of the spatio-temporal heterogeneity in structural organization of IDPs, macromolecular crowding can differently affect structures of different IDPs. Recent studies indicate that some IDPs are able to undergo liquid–liquid-phase transitions leading to the formation of various proteinaceous membrane-less organelles (PMLOs). Although interiors of such PMLOs are self-crowded, being characterized by locally increased concentrations of phase-separating IDPs, these IDPs are minimally foldable or even non-foldable at all (at least within the physiologically safe time-frame of normal PMLO existence).     

Protein kinase D inhibitor CRT0066101 suppresses bladder cancer growth in vitro and xenografts via blockade of the cell cycle at G2/M

The protein kinase D (PKD) family of proteins are important regulators of tumor growth, development, and progression. CRT0066101, an inhibitor of PKD, has antitumor activity in multiple types of carcinomas. However, the effect and mechanism of CRT0066101 in bladder cancer are not understood. In the present study, we show that CRT0066101 suppressed the proliferation and migration of four bladder cancer cell lines in vitro. We also demonstrate that CRT0066101 blocked tumor growth in a mouse flank xenograft model of bladder cancer. To further assess the role of PKD in bladder carcinoma, we examined the three PKD isoforms and found that PKD2 was highly expressed in eight bladder cancer cell lines and in urothelial carcinoma tissues from the TCGA database, and that short hairpin RNA (shRNA)-mediated knockdown of PKD2 dramatically reduced bladder cancer growth and invasion in vitro and in vivo, suggesting that the effect of the compound in bladder cancer is mediated through inhibition of PKD2. This notion was corroborated by demonstrating that the levels of phospho-PKD2 were markedly decreased in CRT0066101-treated bladder tumor explants. Furthermore, our cell cycle analysis by flow cytometry revealed that CRT0066101 treatment or PKD2 silencing arrested bladder cancer cells at the G2/M phase, the arrest being accompanied by decreases in the levels of cyclin B1, CDK1 and phospho-CDK1 (Thr161) and increases in the levels of p27^Kip1 and phospho-CDK1 (Thr14/Tyr15). Moreover, CRT0066101 downregulated the expression of Cdc25C, which dephosphorylates/activates CDK1, but enhanced the activity of the checkpoint kinase Chk1, which inhibits CDK1 by phosphorylating/inactivating Cdc25C. Finally, CRT0066101 was found to elevate the levels of Myt1, Wee1, phospho-Cdc25C (Ser216), Gadd45α, and 14-3-3 proteins, all of which reduce the CDK1-cyclin B1 complex activity. These novel findings suggest that CRT0066101 suppresses bladder cancer growth by inhibiting PKD2 through induction of G2/M cell cycle arrest, leading to the blockade of cell cycle progression.