Abdominal aortic aneurysm (AAA) remains a fatal disease. Its development encompasses a complex interplay between hemodynamic stimuli on and changes in the arterial wall. Currently available biomarkers fail to predict the risk of AAA rupture independent of aneurysm size. Therefore, novel biomarkers for AAA characterization are needed. In this study, we used a mouse model of AAA to investigate the potential of magnetic resonance imaging (MRI) with an albumin-binding probe to assess changes in vascular permeability at different stages of aneurysm growth. Two imaging studies were performed: a longitudinal study with follow-up and death as endpoint to predict rupture risk and a week-by-week study to characterize AAA development. AAAs, which eventually ruptured, demonstrated a significantly higher in vivo MR signal enhancement from the albumin-binding probe (p = 0.047) and a smaller nonenhancing thrombus area compared to intact AAAs (p = 0.001). The ratio of albumin-binding-probe enhancement of the aneurysm wall to size of nonenhancing-thrombus-area predicted AAA rupture with high sensitivity/specificity (100%/86%). More advanced aneurysms with higher vascular permeability demonstrated an increased uptake of the albumin-binding-probe. These results indicate that MRI with an albumin-binding probe may enable noninvasive assessment of vascular permeability in murine AAAs and prediction of rupture risk.

Transition metal monopnictides belong to the new class of semimetals where the bulk properties are determined by the presence of pairs of nodes with different chirality formed by linear dispersive states in the k-space. Beside the anomaly in the bulk magnetotransport superconductivity is frequently found in some Weyl semimetals. We found signatures of superconductivity in ac and dc magnetization measurements of highly pure and stoichiometric NbP powder. We determined the lower and upper critical field and the Ginzburg-Landau parameter. The relative small superconducting volume fraction is related to either effect of finite grain size and/or surface superconductivity. The last mentioned may originate from either off stoichiometric (Nb-rich) surface layers or a strained surface with different electronic properties. Furthermore the intrinsic normal state susceptibility is determined taking into account a paramagnetic contribution of a few ppm of magnetic impurities.

Holographic quantum error-correcting codes have been proposed as toy models that describe key aspects of the anti-de Sitter/conformal field theory (AdS/CFT) correspondence. In this work, we introduce a versatile framework of Majorana dimers capturing the intersection of stabilizer and Gaussian Majorana states. This picture allows for an efficient contraction with a simple diagrammatic interpretation and is amenable to analytical study of holographic quantum error-correcting codes. Equipped with this framework, we revisit the recently proposed hyperbolic pentagon code (HyPeC). Relating its logical code basis to Majorana dimers, we efficiently compute boundary-state properties even for the non-Gaussian case of generic logical input. The dimers characterizing these boundary states coincide with discrete bulk geodesics, leading to a geometric picture from which properties of entanglement, quantum error correction, and bulk/boundary operator mapping immediately follow. We also elaborate upon the emergence of the Ryu-Takayanagi formula from our model, which realizes many of the properties of the recent bit thread proposal. Our work thus elucidates the connection among bulk geometry, entanglement, and quantum error correction in AdS/CFT and lays the foundation for new models of holography.

For more than two decades, there have been reports on an unexpected metallic state separating the established superconducting and insulating phases of thin-film superconductors. To date, no theoretical explanation has been able to fully capture the existence of such a state for the large variety of superconductors exhibiting it. Here, we show that for two very different thin-film superconductors, amorphous indium oxide and a single crystal of 2H-NbSe2, this metallic state can be eliminated by adequately filtering external radiation. Our results show that the appearance of temperature-independent, metallic-like transport at low temperatures is sufficiently described by the extreme sensitivity of these superconducting films to external perturbations. We relate this sensitivity to the theoretical observation that, in two dimensions, superconductivity is only marginally stable.

We present a new open-source Python package, krotov, implementing the quantum optimal control method of that name. It allows to determine time-dependent external fields for a wide range of quantum control problems, including state-to-state transfer, quantum gate implementation and optimization towards an arbitrary perfect entangler. Krotov's method compares to other gradient-based optimization methods such as gradient-ascent and guarantees monotonic convergence for approximately time-continuous control fields. The user-friendly interface allows for combination with other Python packages, and thus high-level customization.

Spin chains with symmetry-protected edge zero modes can be seen as prototypical systems for exploring topological signatures in quantum systems. These are useful for robustly encoding quantum information. However in an experimental realization of such a system, spurious interactions may cause the edge zero modes to delocalize. To stabilize against this influence beyond simply increasing the bulk gap, it has been proposed to harness suitable notions of disorder. Equipped with numerical tools for constructing locally conserved operators that we introduce, we comprehensively explore the interplay of local interactions and disorder on localized edge modes in the XZX cluster Hamiltonian. This puts us in a position to challenge the narrative that disorder necessarily stabilizes topological order. Contrary to heuristic reasoning, we find that disorder has no effect on the edge modes in the Anderson localized regime. Moreover, disorder helps localize only a subset of edge modes in the many-body interacting regime. We identify one edge mode operator that behaves as if subjected to a non-interacting perturbation, i.e., shows no disorder dependence. This implies that in finite systems, edge mode operators effectively delocalize at distinct interaction strengths. In essence, our findings suggest that the ability to identify and control the best localized edge mode trumps any gains from introducing disorder.

Subduction zones are monitored using space geodesy with increasing resolution, with the aim of better capturing the deformation accompanying the seismic cycle. Here, we investigate data characteristics that maximize the performance of a machine learning binary classifier predicting slip‐event imminence. We overcome the scarcity of recorded instances from real subduction zones using data from a seismotectonic analog model monitored with a spatially dense, continuously recording onshore geodetic network. We show that a 70–85 km‐wide coastal swath recording interseismic deformation gives the most important information on slip imminence. Prediction performances are mainly influenced by the alarm duration (amount of time that we consider an event as imminent), with density of stations and record length playing a secondary role. The techniques developed in this study are most likely applicable in regions of slow earthquakes, where stick‐slip‐like failures occur at time intervals of months to years.

The stereoselective formation of 1,2‐cis‐glycosidic bonds is challenging. However, 1,2‐cis‐selectivity can be induced by remote participation of C4 or C6 ester groups. Reactions involving remote participation are believed to proceed via a key ionic intermediate, the glycosyl cation. Although mechanistic pathways were postulated many years ago, the structure of the reaction intermediates remained elusive owing to their short‐lived nature. Herein, we unravel the structure of glycosyl cations involved in remote participation reactions via cryogenic vibrational spectroscopy and first principles theory. Acetyl groups at C4 ensure α‐selective galactosylations by forming a covalent bond to the anomeric carbon in dioxolenium‐type ions. Unexpectedly, also benzyl ether protecting groups can engage in remote participation and promote the stereoselective formation of 1,2‐cis‐glycosidic bonds.

Three bis‐chelates of indium(III) with (partially fluorinated) S,N,S‐tridentate thiosemicarbazones (H2L) were prepared and their structures were studied in solution and in the solid state by NMR, ESI MS and single‐crystal X‐ray diffraction. The three compounds are isostructural in solution with five‐coordinate InIII ions and two differently coordinated thiosemicarbazonato ligands, [In(L)(HL)]. A temperature‐dependent 1H NMR study reflects the presence of dynamic processes in the molecules such as the resolution of hindered rotation around CN bonds with partial double‐bond character and the pH‐triggered isomerization between 5‐ and 6‐coordinate species. The latter is confirmed by the isolation of compounds with different solid‐state structures, [In(L)(HL)] and [In(L)2]–, depending on fluorine‐substitutions in the periphery of the thiosemicarbazones.

Applying broiler litter containing extended-spectrum beta-lactamase (ESBL)–producing Escherichia coli (E. coli) to arable land poses a potential risk for humans to get colonized by contact with contaminated soil or vegetables. Therefore, an inactivation of these bacteria before land application of litter is crucial. We performed 2 short-term litter storage trials (one in summer and winter, respectively), each covering a time span of 5 D to investigate the effectiveness of this method for inactivation of ESBL-producing E. coli in chicken litter. Surface and deep litter samples were taken from a stacked, ESBL-positive chicken litter heap in triplicates in close sampling intervals at the beginning and daily for the last 3 D of the experiments. Samples were analyzed quantitatively and qualitatively for ESBL-producing E. coli, total E. coli, and enterococci. Selected isolates were further characterized by whole-genome sequencing (WGS). In the depth of the heap ESBL-producing E. coli were detected quantitatively until 72 h and qualitatively until the end of the trial in winter. In summer detection was possible quantitatively up to 36 h and qualitatively until 72 h. For surface litter samples a qualitative detection of ESBL-producing E. coli was possible in all samples taken in both trials. In the deep samples a significant decrease in the bacterial counts of over 2 Log10 was observed for total E. coli in the winter and for total E. coli and enterococci in the summer. Genetic differences of the isolates analyzed by WGS did not correlate with survival advantage. In conclusion, short-term storage of chicken litter stacked in heaps is a useful tool for the reduction of bacterial counts including ESBL-producing E. coli. However, incomplete inactivation was observed at the surface of the heap and at low ambient temperatures. Therefore, an extension of the storage period in winter as well as turning of the heap to provide aerobic composting conditions should be considered if working and storage capacities are available on the farms.

Interaction with biological material can alter physicochemical parameters of magnetic nanoparticles and might thereby change their magnetic behavior with potentially important implications for various nanoparticle applications. Little is known about changes of the magnetic behavior that occur during the initial phase of cell binding and uptake. We investigate the magnetic behavior of very small superparamagnetic iron-oxide nanoparticles (VSOP) during initial contact with THP-1 monocytes. We combine real-time magnetic particle spectroscopy (MPS), a fast and sensitive method for specific detection of magnetic nanoparticles in biological specimen with high-pressure-freezing/freeze-substitution transmission electron microscopy (HPF/FS-TEM), enabling us to generate snapshots of the interaction of VSOP with the cellular glycocalyx. MPS reveals significant changes of the dynamic magnetic behavior within seconds after VSOP injection into monocyte suspensions that correlate with the formation of nanoparticle clusters in the glycocalyx. The combination of real-time MPS and HPF/FS-TEM provides an ideal platform to analyze magnetic behaviors of nanoparticles upon interaction with cells and tissues.

Background:

Conjunctival defects can be repaired with several mucosal tissues. The simplicity of harvesting oral mucosa and its wide availability makes it the preferred graft tissue for all indications requiring mucosal grafting. Through analysing the postsurgical outcomes and rate of revisions, this study explores the suitability of oral mucosa grafts, depending on the initial diagnosis. Methods:

We reviewed all the files of patients with a history of oral mucosal graft surgery, performed at our clinic between 2012 and 2018, focusing on complications and revision rates. Results:

In total, we analysed 173 oral mucosa grafts in 131 patients. The most common initial diagnosis was tumour resection, followed by surgical complications, postenucleation socket syndrome, trauma and ocular surface disorders. Complication and revision rates depended highly on the initial diagnosis. Revision rates were highest if the initial diagnosis included ocular surface disorders or chemical trauma. Conclusions:

Oral mucosa grafting (OMG) is the most effective treatment for a wide range of ocular conditions involving conjunctival defects. Conjunctival defects that result from trauma or cicatricial surface diseases seem less suitable for OMG and may benefit from alternative graft tissue or treatment options.

BACKGROUND:

PentixaFor is a promising radiopharmaceutical for positron emission tomography in the detection of different tumor entities and other diseases. Until now, the synthesis of [68Ga]Ga-PentixaFor was reported for the automated synthesis module from Scintomics® only. Our aim was to evaluate the automated synthesis of this radiopharmaceutical on a different module in order to make it available for a broader community.

RESULTS:

The synthesis of [68Ga]Ga-PentixaFor with different amounts of PentixaFor (50 μg, 30 μg and 20 μg) on the Modular Lab PharmTracer (MLPT) from Eckert & Ziegler with the already established synthesis template for [68Ga]Ga-DOTATOC yielded best results with 50 μg PentixaFor for clinical multi-dose application. All different quality control parameters tested (e.g. sterility, stability and radiochemical purity) were in accordance with the European Pharmacopoeia.

CONCLUSIONS:

[68Ga]Ga-PentixaFor was successfully synthesized fully-automated on the synthesis module Modular Lab PharmTracer and can be used for multi-dose application in clinical settings.

We thank Dr. Kalmanovich and colleagues for their comments on our randomized controlled trial on improving medication adherence and quality of life of heart failure (HF) patients by a pharmacist‐led interdisciplinary approach.1 This study showed that pharmacy care safely improved adherence to HF medications and quality of life. These data extend recent consensus statements of both the Canadian Cardiovascular Society guidelines for the management of HF2 and the German clinical practice guideline on chronic HF3 that acknowledge the available evidence of pharmacist care and interdisciplinary care.4, 5 Topics and tasks include prevention of HF, particularly by improving adherence to antihypertensives, providing medication reviews, assuring appropriate self‐medication, and improving both medication safety and adherence.4 We congratulate Kalmanovich et al. to their research plan. Their study will hopefully provide additional randomized evidence for the effects of interdisciplinary care in patients with HF.

Living beings spend their lives and carry out their daily activities interacting with environmental situations that present space-time variations and that involve contact with other life forms, which may behave as commensals or as invaders and/or parasites. The characteristics of the environment, as well as the processes that support the maintenance of life and that characterize the execution of activities of daily life generally present periodic variations, which are mostly synchronized with the light-dark cycle determined by Earth's rotation on its axis. These rhythms with 24-h periodicity, defined as circadian, influence events linked to the interaction between hosts and hosted microorganisms and can dramatically determine the outcome of this interplay. As for the various pathological conditions resulting from host-microorganism interactions, a particularly interesting scenario concerns infections by viruses. When a viral agent enters the body, it alters the biological processes of the infected cells in order to favour its replication and to spread to various tissues. Though our knowledge concerning the mutual influence between the biological clock and viruses is still limited, recent studies start to unravel interesting aspects of the clock-virus molecular interplay. Three different aspects of this interplay are addressed in this mini-review and include the circadian regulation of both innate and adaptive immune systems, the impact of the biological clock on viral infection itself, and finally the putative perturbations that the virus may confer to the clock leading to its deregulation.

Physical activity (PA) in youth tends to decline with increasing age, while sedentary behaviour including screen time (ST) increases. There are adolescents, however, whose PA and ST do not follow this pattern. The aim of this study is (i) to examine trajectories in PA and ST from grade 7-9 among students in Berlin, and (ii) to investigate the relationship of these trajectories with individual factors and school type. For the present analyses, changes in students' PA and ST across three time points from 7th to 9th grade were assessed via self-report questionnaires. Positive and negative trajectories were defined for both PA (positive: increasing or consistently high, negative: decreasing or consistently low) and ST (vice versa). Multivariable logistic regression analyses were performed to identify possible predictors of PA and ST trajectories. In total, 2122 students were included (50.2% girls, mean age 12.5 (standard deviation 0.7) years). Compared to grade 7, less students of grade 9 fulfilled PA and ST recommendations (PA: 9.4% vs. 13.2%; ST: 19.4% vs. 25.0%). The positive PA trajectory included 44% of all students (63% boys), while the positive ST trajectory included 21% of all students (30% boys). Being a boy was significantly associated with a positive PA trajectory, while being a girl, having a high socioeconomic status, and attending a high school, were significantly associated with a positive ST trajectory. Different PA and ST trajectories among adolescents should be taken into account when implementing prevention programs for this target group.

The homing of Endothelial Progenitor Cells (EPCs) to tumor angiogenic sites has been described as a multistep process, involving adhesion, migration, incorporation and sprouting, for which the underlying molecular and cellular mechanisms are yet to be fully defined. Here, we studied the expression of Junctional Adhesion Molecule-C (JAM-C) by EPCs and its role in EPC homing to tumor angiogenic vessels. For this, we used mouse embryonic-Endothelial Progenitor Cells (e-EPCs), intravital multi-fluorescence microscopy techniques and the dorsal skin-fold chamber model. JAM-C was found to be expressed by e-EPCs and endothelial cells. Blocking JAM-C did not affect adhesion of e-EPCs to endothelial monolayers in vitro but, interestingly, it did reduce their adhesion to tumor endothelium in vivo. The most striking effect of JAM-C blocking was on tube formation on matrigel in vitro and the incorporation and sprouting of e-EPCs to tumor endothelium in vivo. Our results demonstrate that JAM-C mediates e-EPC recruitment to tumor angiogenic sites, i.e., coordinated homing of EPCs to the perivascular niche, where they cluster and interact with tumor blood vessels. This suggests that JAM-C plays a critical role in the process of vascular assembly and may represent a potential therapeutic target to control tumor angiogenesis.

Epigenomic regulation plays a vital role in cell differentiation. The leukemic HL-60/S4 [human myeloid leukemic cell line HL-60/S4 (ATCC CRL-3306)] promyelocytic cell can be easily differentiated from its undifferentiated promyelocyte state into neutrophil- and macrophage-like cell states. In this study, we present the underlying genome and epigenome architecture of HL-60/S4 through its differentiation. We performed whole-genome bisulphite sequencing of HL-60/S4 cells and their differentiated counterparts. With the support of karyotyping, we show that HL-60/S4 maintains a stable genome throughout differentiation. Analysis of differential Cytosine-phosphate-Guanine dinucleotide methylation reveals that most methylation changes occur in the macrophage-like state. Differential methylation of promoters was associated with immune-related terms. Key immune genes, CEBPA, GFI1, MAFB and GATA1 showed differential expression and methylation. However, we observed the strongest enrichment of methylation changes in enhancers and CTCF binding sites, implying that methylation plays a major role in large-scale transcriptional reprogramming and chromatin reorganisation during differentiation. Correlation of differential expression and distal methylation with support from chromatin capture experiments allowed us to identify putative proximal and long-range enhancers for a number of immune cell differentiation genes, including CEBPA and CCNF Integrating expression data, we present a model of HL-60/S4 differentiation in relation to the wider scope of myeloid differentiation.

Purpose of Review:

This review brings together recent research on the structure, characteristics, dynamics, and impacts of extratropical cyclones in the future. It draws on research using idealized models and complex climate simulations, to evaluate what is known and unknown about these future changes. Recent Findings:

There are interacting processes that contribute to the uncertainties in future extratropical cyclone changes, e.g., changes in the horizontal and vertical structure of the atmosphere and increasing moisture content due to rising temperatures. Summary:

While precipitation intensity will most likely increase, along with associated increased latent heating, it is unclear to what extent and for which particular climate conditions this will feedback to increase the intensity of the cyclones. Future research could focus on bridging the gap between idealized models and complex climate models, as well as better understanding of the regional impacts of future changes in extratropical cyclones.

Cataracts are focal to diffuse opacities of the eye lens causing impaired vision or complete blindness. For bilateral congenital cataracts in Red Holsteins a perfectly cosegregating mutation within the CPAMD8 gene (CPAMD8:g.5995966C>T) has been reported. We genotyped the CPAMD8:g.5995966C>T variant in Holstein calves affected by congenital bilateral congenital cataracts, their unaffected relatives and randomly selected herd mates. Ophthalmological examinations were performed in all affected individuals to confirm a congenital cataract. Whole genome sequencing was employed to screen variants in candidate genes for the Morgagnian cataract phenotype. In the present study, 3/35 cases were confirmed as homozygous mutated and 6/14 obligate carriers. Further 7/46 unaffected animals related with these cases were heterozygous mutated for the CPAMD8:g.5995966C>T variant. However 32 cases with a congenital cataract showed the wild type for the CPAMD8 variant. We did not identify variants in the candidate genes CPAMD8 and NID1 or in their close neighborhood as strongly associated with the congenital cataract phenotype in Holstein calves with the CPAMD8 wild type. In conclusion, the CPAMD8:g.5995966C>T variant is insufficient to explain the majority of Morgagnian congenital cataract phenotypes in Holsteins. It is very likely that congenital bilateral cataracts may be genetically heterogeneous and not yet known variants in genes other than CPAMD8 and NID1 are involved.