Inside Ceramics and Between MgO Grains: Solid-State Synthesis of Intergranular Semiconducting or Magnetic Spinels.

Configurations of composite metal oxide nanoparticles are typically far off their thermodynamic equilibrium state. As such they represent a versatile but so far overlooked source material for the intergranular solid-state chemistry inside ceramics. Here, it is demonstrated how the admixture of Fe and In ions to MgO nanoparticles, as achieved by flame spray pyrolysis, can be used to engage ion exsolution, phase separation, and subsequent spinel formation inside the network of diamagnetic and insulating MgO grains.

Smooth muscle cell phenotypic switching occurs independent of aortic dilation in bicuspid aortic valve-associated ascending aortas.

Background: Bicuspid aortic valves (BAV) are frequently associated with ascending aortic aneurysms. The etiology is incompletely understood, but genetic factors, in addition to flow perturbations, are likely involved. Since loss of contractility and elaboration of extracellular matrix in the vessel wall are features of BAV-associated aortopathy, phenotypic modulation of smooth muscle cells (SMCs) may play a role.

Predicting multimodal chromatography of therapeutic antibodies using multiscale modeling.

Multimodal chromatography has emerged as a powerful method for the purification of therapeutic antibodies. However, process development of this separation technique remains challenging because of an intricate and molecule-specific interaction towards multimodal ligands, leading to time-consuming and costly experimental optimization. This study presents a multiscale modeling approach to predict the multimodal chromatographic behavior of therapeutic antibodies based on their sequence information.

Nuclear Abnormalities in p.(Glu2Lys) Variant Segregating with -Associated Cardiocutaneous Progeria Syndrome.

The gene encodes lamin A and lamin C, which play important roles in nuclear organization. Pathogenic variants in cause laminopathies, a group of disorders with diverse phenotypes. There are two main groups of disease-causing variants: missense variants affecting dimerization and intermolecular interactions, and heterozygous substitutions activating cryptic splice sites.

Oxygen Radicals Entrapped between MgO Nanocrystals: Formation, Spectroscopic Fingerprints, and Reactivity toward Water.

Compaction of dehydroxylated MgO nanocrystal powders produces adsorbed oxygen radicals with characteristic UV-vis spectroscopic fingerprints. Identical absorption bands arise upon UV excitation in an oxygen atmosphere but in the absence of uniaxial pressure. Photophysical calculations on MgO gas-phase clusters reveal that the observed optical transitions at 4.

Antibody sequence-based prediction of pH gradient elution in multimodal chromatography.

Multimodal chromatography has emerged as a promising technique for antibody purification, owing to its capacity to selectively capture and separate target molecules. However, the optimization of chromatography parameters remains a challenge due to the intricate nature of protein-ligand interactions. To tackle this issue, efficient predictive tools are essential for the development and optimization of multimodal chromatography processes.

Aortic regurgitation provokes phenotypic modulation of smooth muscle cells in the normal ascending aorta.

Background: Aortic complications are more likely to occur in patients with ascending aortic aneurysms and concomitant aortic regurgitation (AR). AR may have a negative influence on the aortic wall structure even in patients with tricuspid aortic valves and absence of aortic dilatation. It is unknown whether smooth muscle cell (SMC) changes are a feature of AR-associated aortic remodeling.

Bi-allelic variants in HMGCR cause an autosomal-recessive progressive limb-girdle muscular dystrophy.

Statins are a mainstay intervention for cardiovascular disease prevention, yet their use can cause rare severe myopathy. HMG-CoA reductase, an essential enzyme in the mevalonate pathway, is the target of statins. We identified nine individuals from five unrelated families with unexplained limb-girdle like muscular dystrophy and bi-allelic variants in HMGCR via clinical and research exome sequencing.

Conversion of MgO nanocrystal surfaces into ceramic interfaces: Exsolution of BaO as photoluminescent interface probes.

Ion exsolution can be instrumental to engineer intergranular regions inside ceramic microstructures. BaO admixtures that were trapped inside nanometer-sized MgO grains during gas phase synthesis undergo annealing-induced exsolution to generate photoluminescent surface and interface structures. During their segregation from the bulk into the grain interfaces, the BaO admixtures impact grain coarsening and powder densification, effects that were compared for the first time using an integrated characterization approach.

Bi-allelic variants in INTS11 are associated with a complex neurological disorder.

The Integrator complex is a multi-subunit protein complex that regulates the processing of nascent RNAs transcribed by RNA polymerase II (RNAPII), including small nuclear RNAs, enhancer RNAs, telomeric RNAs, viral RNAs, and protein-coding mRNAs. Integrator subunit 11 (INTS11) is the catalytic subunit that cleaves nascent RNAs, but, to date, mutations in this subunit have not been linked to human disease. Here, we describe 15 individuals from 10 unrelated families with bi-allelic variants in INTS11 who present with global developmental and language delay, intellectual disability, impaired motor development, and brain atrophy.

Population-Based Severe Acute Respiratory Syndrome Coronavirus 2 Whole-Genome Sequencing and Contact Tracing During the Coronavirus Disease 2019 Pandemic in Switzerland.

Background: Testing and contact tracing (CT) can interrupt transmission chains of SARS-CoV-2. Whole-genome sequencing (WGS) can potentially strengthen these investigations and provide insights on transmission.

Methods: We included all laboratory-confirmed COVID-19 cases diagnosed between 4 June and 26 July 2021, in a Swiss canton.

Age-dependent phenotypic modulation of smooth muscle cells in the normal ascending aorta.

Objectives: Ascending aortic aneurysms are associated with pre-existing conditions, including connective tissue disorders (i.e., Marfan syndrome) and bicuspid aortic valves.

Charge Separation in BaTiO Nanocrystals: Spontaneous Polarization Versus Point Defect Chemistry.

The fate of photogenerated charges within ferroelectric metal oxides is key for photocatalytic applications. The authors study the contributions of i) tetragonal distortion, responsible for spontaneous polarization, and ii) point defects, on charge separation and recombination within BaTiO (BTO) nanocrystals of cubic and tetragonal structure. Electron paramagnetic resonance (EPR) in combination with O photoadsorption experiments show that BTO nanocrystals annealed at 600 °C have a charge separation yield enhanced by a factor > 10 compared to TiO anatase nanocrystals of similar geometries.

Standardized method for mechanistic modeling of multimodal anion exchange chromatography in flow through operation.

Multimodal chromatography offers an increased selectivity compared to unimodal chromatographic methods and is often employed for challenging separation tasks in industrial downstream processing (DSP). Unfortunately, the implementation of multimodal polishing into a generic downstream platform can be hampered by non-robust platform conditions leading to a time and cost intensive process development. Mechanistic modeling can assist experimental process development but readily applicable and easy to calibrate multimodal chromatography models are lacking.

Applying intensified design of experiments to mammalian cell culture processes.

The analysis of data collected using design of experiments (DoE) is the current gold standard to determine the influence of input parameters and their interactions on process performance and product quality. In early development, knowledge on the bioprocess of a new product is limited. Many input parameters need to be investigated for a thorough investigation.

A multiscale modeling method for therapeutic antibodies in ion exchange chromatography.

The development of biopharmaceutical downstream processes relies on exhaustive experimental studies. The root cause is the poorly understood relationship between the protein structure of monoclonal antibodies (mAbs) and their macroscopic process behavior. Especially the development of preparative chromatography processes is challenged by the increasing structural complexity of novel antibody formats and accelerated development timelines.

A Primer Genetic Toolkit for Exploring Mitochondrial Biology and Disease Using Zebrafish.

Mitochondria are a dynamic eukaryotic innovation that play diverse roles in biology and disease. The mitochondrial genome is remarkably conserved in all vertebrates, encoding the same 37-gene set and overall genomic structure, ranging from 16,596 base pairs (bp) in the teleost zebrafish () to 16,569 bp in humans. Mitochondrial disorders are amongst the most prevalent inherited diseases, affecting roughly 1 in every 5000 individuals.

Bariatric Weight Loss Surgery Improves Systolic Function in Obese Patients With Heart Failure.

Obesity has become a worldwide public health issue. Many obese patients concomitantly suffer with heart failure with reduced ejection fraction. There have been reports of improvement in left ventricular systolic function following significant weight loss after bariatric surgery.

Rubbing Powders: Direct Spectroscopic Observation of Triboinduced Oxygen Radical Formation in MgO Nanocube Ensembles.

Powder compaction-induced surface chemistry in metal oxide nanocrystal ensembles is important for very diverse fields such as triboelectrics, tribocatalysts, surface abrasion, and cold sintering of ceramics. Using a range of spectroscopic techniques, we show that MgO nanocube powder compaction with uniaxial pressures that can be achieved by gentle manual rubbing or pressing ( ≥ 5 MPa) excites energetic electron-hole pairs and generates oxygen radicals at interfacial defect structures. While the identification of paramagnetic O radicals and their adsorption complexes with O point to the emergence of hole centers, triboemitted electrons become scavenged by molecular oxygen to convert into adsorbed superoxide anions O as measured by electron paramagnetic resonance (EPR).

Clinicopathologic Characteristics, Treatment, and Outcomes of Post-transplant Lymphoproliferative Disorders: A Single-institution Experience Using 2017 WHO Diagnostic Criteria.

The (WHO 2017) included updated criteria for diagnosis and classification of post-transplant lymphoproliferative disorders (PTLDs). This study evaluated the clinicopathologic spectrum using WHO 2017 criteria and adult PTLD patients' outcomes over 30 years between 1987 and 2017 at Mayo Clinic (Rochester, MN). Patients were retrospectively reviewed for clinical features, outcomes, and diagnostic pathology material and classified based on WHO 2017 criteria.

Designed architectural proteins that tune DNA looping in bacteria.

Architectural proteins alter the shape of DNA. Some distort the double helix by introducing sharp kinks. This can serve to relieve strain in tightly-bent DNA structures.

Cubes to Cubes: Organization of MgO Particles into One-Dimensional and Two-Dimensional Nanostructures.

Developing simple, inexpensive, and environmentally benign approaches to integrate morphologically well-defined nanoscale building blocks into larger high surface area materials is a key challenge in materials design and processing. In this work, we investigate the fundamental surface phenomena between MgO and water (both adsorption and desorption) with particles prepared via a vapor-phase process (MgO nanocubes) and a modified aerogel process (MgO(111) nanosheets). Through these studies, we unravel a strategy to assemble individual MgO nanoparticles into extended faceted single-crystalline MgO nanosheets and nanorods with well-defined exposed surfaces and edges.