Molecular dynamics simulations of the dipolar-induced formation of magnetic nanochains and nanorings

Iron, cobalt and nickel nanoparticles, grown in the gas phase, are known to arrange in chains and bracelet-like rings due to the long-range dipolar interaction between the ferromagnetic (or super-paramagnetic) particles. We investigate the dynamics and thermodynamics of such magnetic dipolar nanoparticles for low densities using molecular dynamics simulations and analyze the influence of temperature and external magnetic fields on two- and three-dimensional systems. The obtained phase diagrams can be understood by using simple energetic arguments.Comment: 6 pages, 6 figure

Postprandial transfer of colostral extracellular vesicles and their protein and miRNA cargo in neonatal calves

Extracellular vesicles (EVs) such as exosomes are key regulators of intercellular communication that can be found in almost all bio fluids. Although studies in the last decade have made great headway in discerning the role of EVs in many physiological and pathophysiological processes, the bioavailability and impact of dietary EVs and their cargo still remain to be elucidated. Due to its widespread consumption and high content of EV-associated microRNAs and proteins, a major focus in this field has been set on EVs in bovine milk and colostrum. Despite promising in vitro studies in recent years that show high resiliency of milk EVs to degradation and uptake of milk EV cargo in a variety of intestinal and blood cell types, in vivo experiments continue to be inconclusive and sometimes outright contradictive. To resolve this discrepancy, we assessed the potential postprandial transfer of colostral EVs to the circulation of newborn calves by analysing colostrum-specific protein and miRNAs, including specific isoforms (isomiRs) in cells, EV isolations and unfractionated samples from blood and colostrum. Our findings reveal distinct populations of EVs in colostrum and blood from cows that can be clearly separated by density, particle concentration and protein content (BTN1A1, MFGE8). Postprandial blood samples of calves show a time-dependent increase in EVs that share morphological and protein characteristics of colostral EVs. Analysis of miRNA expression profiles by Next-Generation Sequencing gave a different picture however. Although significant postprandial expression changes could only be detected for calf EV samples, expression profiles show very limited overlap with highly expressed miRNAs in colostral EVs or colostrum in general. Taken together our results indicate a selective uptake of membrane-associated protein cargo but not luminal miRNAs from colostral EVs into the circulation of neonatal calves

Can true papillary neoplasms of breast and their mimickers be accurately classified by cytology?

BACKGROUND The cytologic accuracy in assessing malignancy in papillary breast neoplasms (PBNs) is controversial. This is further complicated by overlapping features observed in other breast lesions that produce papillary-like tissue fragments. METHODS The authors reviewed 22 fine-needle aspirates (FNAs) from histologically proven papillary neoplasms: papillary carcinoma (PCA; 10 aspirates) and intraductal papilloma (IDP; 12 aspirates). They also reviewed 8 FNAs in which a papillary neoplasm was suggested by cytology but not confirmed by follow-up biopsy: fibroadenoma (6), mucinous carcinoma (1), and cribriform ductal carcinoma in situ (1). RESULTS Papillary carcinoma can be distinguished from IDP by the higher cellularity, more complex papillae with thin disorganized fronds, mild to moderate nuclear atypia, and prominent dissociation with many single papillae. Fibrovascular cores (FVCs) were more common in PCA than IDP in which detached fibrous tissue fragments were frequently seen. Atypical IDP exhibited features intermediate between PCA and IDP. Apocrine metaplasia was variably present in IDP, atypical IDP, and fibroadenoma but absent in all carcinomas. Intraductal papilloma can be distinguished from fibroadenoma by their broad ruffled branches, scalloped borders, and tiny tongue-like projections. True papillae were commonly covered by tall columnar cells. Myoepithelial cells were few in IDP but were numerous in fibroadenoma. The epithelial fragments in nonpapillary lesions presented as cellular spheres and/or complex sheets with finger-like projections but lacked FVCs and columnar cells. CONCLUSIONS Papillary breast neoplasms can be accurately classified by cytology. Closer evaluation of the tissue fragments architecture and the background can help in separating PBN from their mimics. Cancer (Cancer Cytopathol) 2002;96:000–000. © 2002 American Cancer Society.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/34364/1/10481_ftp.pd

Toward reliable biomarker signatures in the age of liquid biopsies - how to standardize the small RNA-Seq workflow

Small RNA-Seq has emerged as a powerful tool in transcriptomics, gene expression profiling and biomarker discovery. Sequencing cell-free nucleic acids, particularly microRNA (miRNA), from liquid biopsies additionally provides exciting possibilities for molecular diagnostics, and might help establish disease-specific biomarker signatures. The complexity of the small RNA-Seq workflow, however, bears challenges and biases that researchers need to be aware of in order to generate high-quality data. Rigorous standardization and extensive validation are required to guarantee reliability, reproducibility and comparability of research findings. Hypotheses based on flawed experimental conditions can be inconsistent and even misleading. Comparable to the well-established MIQE guidelines for qPCR experiments, this work aims at establishing guidelines for experimental design and pre-analytical sample processing, standardization of library preparation and sequencing reactions, as well as facilitating data analysis. We highlight bottlenecks in small RNA-Seq experiments, point out the importance of stringent quality control and validation, and provide a primer for differential expression analysis and biomarker discovery. Following our recommendations will en-courage better sequencing practice, increase experimental transparency and lead to more reproducible small RNA-Seq results. This will ultimately enhance the validity of biomarker signatures, and allow reliable and robust clinical predictions

Potassium binding adjacent to cationic transition metal fragments: unusual heterobimetallic adducts of a calix[4]arene-based thione ligand

The synthesis of cationic rhodium and iridium complexes of a bis(imidazol-2-thione) functionalised calix[4]arene ligand and their surprising capacity for potassium binding is described. In both cases uptake of the alkali metal into the calix[4]arene cavity occurs despite adverse electrostatic interactions associated with close proximity to the transition metal fragment (Rh+∙∙∙K+ = 3.715(1) Å, Ir+∙∙∙K+ = 3.690(1) Å). The formation and constituent bonding of these unusual heterobimetallic adducts has been interrogated through extensive solution and solid-state characterisation, examination of the host-guest chemistry of the ligand and its upper-rim unfunctionalised calix[4]arene analogue, and computationally using DFT-based energy decomposition analysis (EDA)

Iridium complexes of the conformationally rigid IBioxMe4Ligand : hydride complexes and dehydrogenation of cyclooctene

A method for accessing the formally 14 VE iridium(III) hydride fragment {Ir(IBioxMe4)2(H)2}+ (2), containing the conformationally rigid NHC ligand IBioxMe4, is reported. Hydrogenation of trans-[Ir(IBioxMe4)2(COE)Cl] (1) in the presence of excess Na[BArF4] leads to the formation of dimeric [{Ir(IBioxMe4)2(H)2}2Cl][BArF4] (3), which is structurally fluxional in solution and acts as a reservoir of monomeric 2 in the presence of excess halogen ion abstractor. Stable dihydride complexes trans-[Ir(IBioxMe4)2(2,2′-bipyridine)(H)2][BArF4] (4) and [Ir(IBioxMe4)3(H)2][BArF4] (5) were subsequently isolated through in situ trapping of 2 using 2,2′-bipyridine and IBioxMe4, respectively, and fully characterized. Using mixtures of 3 and Na[BArF4] as a latent source of 2, the reactive monomeric fragment’s reactivity was explored with excess ethylene and cyclooctene, and trans-[Ir(IBioxMe4)2(C2H4)2][BArF4] (6) and cis-[Ir(IBioxMe4)2(COD)][BArF4] (7) were isolated, respectively, through sacrificial hydrogenation of the alkenes. Complex 6 is notable for the adoption of a very unusual orthogonal arrangement of the trans-ethylene ligands in the solid state, which has been analyzed computationally using energy and charge decomposition (EDA-NOCV). The formation of 7 via transfer dehydrogenation of COE highlights the ability to partner IBioxMe4 with reactive metal centers capable of C–H bond activation, without intramolecular activation. Reaction of 7 with CO slowly formed trans-[Ir(IBioxMe4)2(CO)2][BArF4] (8), but the equivalent reaction with bis-ethylene 6 was an order of magnitude faster, quantifying the strong coordination of COD in 7

Rhodium(I) and Iridium(I) complexes of the conformationally rigid IBioxMe4Ligand : computational and experimental studies of unusually tilted NHC coordination geometries

Computational methods have been used to analyze distorted coordination geometries in a coherent range of known and new rhodium(I) and iridium(I) complexes containing bioxazoline-based NHC ligands (IBiox). Such distortions are readily placed in context of the literature through measurement of the Cnt(NHC)–CNCN–M angle (ΘNHC; Cnt = ring centroid). On the basis of restricted potential energy calculations using cis-[M(IBioxMe4)(CO)2Cl] (M1; M = Rh, Ir), in-plane (yawing) tilting of the NHC was found to incur significantly steeper energetic penalties than orthogonal out-of-plane (pitching) movement, which is characterized by noticeably flat potential energy surfaces. Energy decomposition analysis (EDA) of the ground-state and pitched structures of M1 indicated only minor differences in bonding characteristics. In contrast, yawing of the NHC ligand is associated with a significant increase in Pauli repulsion (i.e., sterics) and reduction in M→NHC π back donation, but is counteracted by supplemental stabilizing bonding interactions only possible due to the closer proximity of the methyl substituents with the metal and ancillary ligands. Aided by this analysis, comparison with a range of carefully selected model systems and EDA, distorted coordination modes in trans-[M(IBioxMe4)2(COE)Cl] (M2; M = Rh, Ir) and [M(IBioxMe4)3]+ (M3; M = Rh, Ir) have been rationalized. Steric interactions were identified as the major contributing factor and are associated with a high degree of NHC pitching. In the case of Rh3, weak agostic interactions also contribute to the distortions, particularly with respect to NHC yawing, and are notable for increasing the bond dissociation energy of the distorted ligands. Supplementing the computational analysis, an analogue of the formally 14 VE Rh(I) species Rh3 bearing the cyclohexyl-functionalized IBiox6 ligand ([Rh(IBiox6)3]+, Rh3-Cy) was prepared and found to exhibit an exceptionally distorted NHC ligand (ΘNHC = 155.7(2)°) in the solid state

The role of particle precipitation on plasma structuring at different altitudes by in-situ measurements

The plasma in the cusp ionosphere is subject to particle precipitation, which is important for the development of large-scale irregularities in the plasma density. These irregularities can be broken down into smaller scales which have been linked to strong scintillations in the Global Navigation Satellite System (GNSS) signals. We present power spectra for the plasma density irregularities in the cusp ionosphere for regions with and without auroral particle precipitation based on in-situ measurements from the Twin Rockets to Investigate Cusp Electrodynamics-2 (TRICE-2) mission, consisting of two sounding rockets flying simultaneously at different altitudes. The electron density measurements taken from the multi-needle Langmuir probe system (m-NLP) were analyzed for the whole flight duration for both rockets. Due to their high sampling rates, the probes allow for a study of plasma irregularities down to kinetic scales. A steepening of the slope in the power spectra may indicate two regimes, a frequency interval with a shallow slope, where fluid-like processes are dominating, and an interval with a steeper slope which can be addressed with kinetic theory. The steepening occurs at frequencies between 20 Hz and 100 Hz with a median similar to the oxygen gyrofrequency. Additionally, the occurrence of double slopes increases where precipitation starts and throughout the rest of the flight. In addition, strong electron density fluctuations were found in regions poleward of the cusp, thus in regions immediately after precipitation. Furthermore, by investigating the integrated power of the fluctuations within different frequency ranges, we show that at low frequencies (10–100 Hz), the power is pronounced more evenly while the rocket encounters particle precipitation, while at high frequencies (100–1000 Hz) fluctuations essentially coincide with the passing through a flow channel