bluuebunny/crossref_metadata_2025 huggingface dataset:
Origin of Ferroelectric Phase Stabilization via the Clamping Effect in Ferroelectric Hafnium Zirconium Oxide Thin Films
Authors: Fields Shelby S. , Cai Truong , Jaszewski Samantha T. , Salanova Alejandro , Mimura Takanori , Heinrich Helge H. , Henry Michael David , Kelley Kyle P. , Sheldon Brian W. , Ihlefeld Jon F.
Published: August 2022

The presence of the top electrode on hafnium oxide‐based thin films during processing has been shown to drive an increase in the amount of metastable ferroelectric orthorhombic phase and polarization performance. This “Clamping Effect,” also referred to as the Capping or Confinement Effect, is attributed to the mechanical stress and confinement from the top electrode layer. However, other contributions to orthorhombic phase stabilization have been experimentally reported, which may also be affected by the presence of a top electrode. In this study, it is shown that the presence of the top electrode during thermal processing results in larger tensile biaxial stress magnitudes and concomitant increases in ferroelectric phase fraction and polarization response, whereas film chemistry, microstructure, and crystallization temperature are not affected. Through etching experiments and measurement of stress evolution for each processing step, it is shown that the top electrode locally inhibits out‐of‐plane expansion in the HZO during crystallization, which prevents equilibrium monoclinic phase formation and stabilizes the orthorhombic phase. This study provides a mechanistic understanding of the clamping effect and orthorhombic phase formation in ferroelectric hafnium oxide‐based thin films, which informs the future design of these materials to maximize ferroelectric phase purity and corresponding polarization behavior.
Unexplained regression in Down syndrome: Management of 51 patients in an international patient database
Authors: Santoro Stephanie L. , Baumer Nicole T. , Cornacchia Michelle , Franklin Catherine , Hart Sarah J. , Haugen Kelsey , Hojlo Margaret A. , Horick Nora , Kishnani Priya S. , Krell Kavita , McCormick Andrew , Milliken Anna L. , Oreskovic Nicolas M. , Pawlowski Katherine G. , Sargado Sabrina , Torres Amy , Valentini Diletta , Vellody Kishore , Skotko Brian G.
Published: August 2022

Research to guide clinicians in the management of the devastating regression which can affect adolescents and young adults with Down syndrome is limited. A multi‐site, international, longitudinal cohort of individuals with a clinical diagnosis of Unexplained Regression in Down syndrome (URDS) was collated through seven Down syndrome clinics. Tiered medical evaluation, a 28‐item core symptom list, and interim management are described naturalistically. Improvement—defined by the percentage of baseline function on a Parent‐reported Functional Score, overall improvement in symptoms on a Clinician‐administered Functional Assessment, or report of management type being associated with improvement—was analyzed. Improvement rates using ECT, IVIG, and others were compared. Across seven clinics, 51 patients with URDS had regression at age 17.6 years, on average, and showed an average 14.1 out of 28 symptoms. Longitudinal improvement in function was achieved in many patients and the medical management, types of treatment, and their impact on function are described. Management with intravenous immunoglobulin (IVIG) was significantly associated with higher rate of improvement in symptoms at the next visit (p = 0.001). Our longitudinal data demonstrates that URDS is treatable, with various forms of clinical management and has a variable course. The data suggests that IVIG may be an effective treatment in some individuals. Our description of the management approaches used in this cohort lays the groundwork for future research, such as development of standardized objective outcome measure and creation of a clinical practice guideline for URDS.
Atomic‐Scale View of Protein‐PEG Interactions that Redirect the Thermal Unfolding Pathway of PEGylated Human Galectin‐3
Authors: Pritzlaff Amanda , Ferré Guillaume , Mulry Emma , Lin Ling , Gopal Pour Niloofar , Savin Daniel A. , Harris Michael E. , Eddy Matthew T.
Published: August 2022

PEGylation is a promising approach to address the central challenge of applying biologics, i.e., lack of protein stability in the demanding environment of the human body. Wider application is hindered by lack of atomic level understanding of protein‐PEG interactions, preventing design of conjugates with predicted properties. We deployed an integrative structural and biophysical approach to address this critical challenge with the PEGylated carbohydrate recognition domain of human galectin‐3 (Gal3C), a lectin essential for cell adhesion and potential biologic. PEGylation dramatically increased Gal3C thermal stability, forming a stable intermediate and redirecting its unfolding pathway. Structural details revealed by NMR pointed to a potential role of PEG localization facilitated by charged residues. Replacing these residues subtly altered the protein‐PEG interface and thermal unfolding behavior, providing insight into rationally designing conjugates while preserving PEGylation benefits.
Perovskite Photocatalytic CO2 Reduction or Photoredox Organic Transformation?
Authors: San Martin Jovan , Dang Nhu , Raulerson Emily , Beard Matthew C. , Hartenberger Joseph , Yan Yong
Published: August 2022

Metal‐halide perovskites have been explored as photocatalysts for CO2 reduction. We report that perovskite photocatalytic CO2 reduction in organic solvents is likely problematic. Instead, the detected products (i.e., CO) likely result from a photoredox organic transformation involving the solvent. Our observations have been validated using isotopic labeling experiments, band energy analysis, and new control experiments. We designed a typical perovskite photocatalytic setup in organic solvents that led to CO production of up to ≈1000 μmol g−1 h−1. CO2 reduction in organic solvents must be studied with extra care because photoredox organic transformations can produce orders of magnitude higher rate of CO or CH4 than is typical for CO2 reduction routes. Though CO2 reduction is not likely to occur, in situ CO generation is extremely fast. Hence a suitable system can be established for challenging organic reactions that use CO as a feedstock but exploit the solvent as a CO surrogate.
Sunk‐Cost Bias and Knowing When to Terminate a Research Project
Authors: Perignat Elaine , Fleming Fraser F.
Published: August 2022

Scientific research is an open‐ended quest where success usually triumphs over failure. The tremendous success of science obscures the tendency for the non‐linear discovery process to take longer and cost more than expected. Perseverance through detours and past setbacks requires a significant commitment that is fueled by scientific optimism; the same optimism required to overcome challenges simultaneously exacerbates the very human tendency to continue a line of inquiry when the likelihood of success is minimal, the so‐called sunk‐cost bias. This Viewpoint Article shows how the psychological phenomenon of sunk‐cost bias influences medicinal, pharmaceutical, and organic chemists by comparing how the respective industrial and academic practitioners approach sunk‐cost bias; a series of interviews and illustrative quotes provide a rich trove of data to address this seldom discussed, yet potentially avoidable research cost. The concluding strategies recommended for mitigating against sunk‐cost bias should benefit not only medicinal, pharmaceutical, and organic chemists but a wide array of chemistry practitioners.
A Chemically Recyclable Crosslinked Polymer Network Enabled by Orthogonal Dynamic Covalent Chemistry
Authors: Deng Yuanxin , Zhang Qi , Qu Da‐Hui , Tian He , Feringa Ben L.
Published: August 2022

Chemical recycling of synthetic polymers offers a solution for developing sustainable plastics and materials. Here we show that two types of dynamic covalent chemistry can be orthogonalized in a solvent‐free polymer network and thus enable a chemically recyclable crosslinked material. Using a simple acylhydrazine‐based 1,2‐dithiolane as the starting material, the disulfide‐mediated reversible polymerization and acylhydrazone‐based dynamic covalent crosslinking can be combined in a one‐pot solvent‐free reaction, resulting in mechanically robust, tough, and processable crosslinked materials. The dynamic covalent bonds in both backbones and crosslinkers endow the network with depolymerization capability under mild conditions and, importantly, virgin‐quality monomers can be recovered and separated. This proof‐of‐concept study show opportunities to design chemically recyclable materials based on the dynamic chemistry toolbox.
An Organic Laser Based on Thermally Activated Delayed Fluorescence with Aggregation‐Induced Emission and Local Excited State Characteristics
Authors: Li Shuai , Chen Jingyao , Wei Yuling , De Jianbo , Geng Hua , Liao Qing , Chen Runfeng , Fu Hongbing
Published: August 2022

The spatial separation between the highest occupied and the lowest unoccupied molecular orbitals (HOMO and LUMO) in thermally activated delayed fluorescent (TADF) molecules leads to charge transfer (CT) states, which degrade the oscillator strength of emission transition and sacrifices high solid‐state photoluminescence quantum yield (PLQY), together limiting its application in organic solid‐state lasers (OSSLs). Here, we demonstrated organic microwire lasers from TADF emitters that combine aggregation induced emission (AIE) and local excited (LE) state characteristics. The unique AIE and LE feature lead to a PLQY approaching 50 % and a high optical gain of 870 cm−1 for TADF microwires. The regenerated singlet excitons by reverse intersystem crossing (RISC) process are conducive to population inversion. As a result, we demonstrated microwire lasers around 465 nm with a low threshold of 3.74 μJ cm−2. Therefore, our work provides insight to design TADF materials for OSSLs.
Synthesis of a Hexachloro Sulfate(IV) Dianion Enabled by Polychloride Chemistry
Authors: Voßnacker Patrick , Wüst Alisa , Müller Carsten , Kleoff Merlin , Riedel Sebastian
Published: August 2022

The preparation and structural characterization of [NEt3Me]2[SCl6] is described, which is the first example of a [SCl6]2− dianion and of a halosulfate anion of the type [SxXy]z− in general. This dianion belongs to the group of 14‐valence electron AB6E systems and forms an octahedral structure in the solid‐state. Interestingly, co‐crystallization with CH2Cl2 affords [NEt3Me]2[SCl6]⋅4 CH2Cl2 containing [SCl6]2− dianions with C4v symmetry. As suggested by quantum‐chemical calculations, the distortion of the structure is not caused by a stereochemically active lone pair but by enhanced hydrogen bonding interactions with CH2Cl2. At elevated temperatures, [NEt3Me]2[SCl6] decomposes to various sulfur chlorine compounds as shown by Raman spectroscopy. Cooling back to room temperature results in the selective formation of [NEt3Me]2[SCl6] which is comparable to the well‐studied SCl4.
Megalo‐Cavitands: Synthesis of Acridane[4]arenes and Formation of Large, Deep Cavitands for Selective C70 Uptake
Authors: Pfeuffer‐Rooschüz Jonathan , Heim Salome , Prescimone Alessandro , Tiefenbacher Konrad
Published: August 2022

Deep cavitands, concave molecular containers, represent an important supramolecular host class that has been explored for a variety of applications ranging from sensing, switching, purification and adsorption to catalysis. A major limitation in the field has been the cavitand volume that is restricted by the size of the structural platform utilized (diameter approx. 7 Å). We here report the synthesis of a novel, unprecedentedly large structural platform, named acridane[4]arene (diameter approx. 14 Å), suitable for the construction of cavitands with volumes of up to 814 Å3. These megalo‐cavitands serve as size‐selective hosts for fullerenes with mM to sub‐μM binding affinity for C60 and C70. Furthermore, the selective binding of fullerene C70 in the presence of C60 was demonstrated.
Selection of promising lines for yield and quality traits in advanced segregating generation of linseed
Authors: Abtahi Mozhgan , Mirlohi Aghafakhr , Zare Sara
Published: August 2022

Linseed (Linum usitatissimum L.) is becoming more important due to its unique nutrient profile and a source of high‐added value raw material, for both food and industrial uses. However, low productivity and lack of combined quality traits has limited its cultivation and there is an urgent need to develop improved varieties through genetic recombination of traits. In this respect 96 linseed F4 families, derived from eight contrasting parents were field evaluated during 2019–2020. A reasonable diversity among the F4 families indicated a considerable potential for improving linseed for agronomic and quality traits. Results demonstrated that strict selection for oil content, protein content, fatty acid composition and amino acid profile, with comparatively high heritability and genetic advance, is feasible and successful in F4 generation. Families with linolenic acid content as low as 9.26% and as high as 72.46% were identified. Yellow‐seeded families had higher values of phenological traits, plant height and number of capsules and lower values of seed number, linolenic acid, palmitic acid, stearic acid, aspartic acid, leucine and lysine content than the brown‐seeded types. Among the many low linolenic acid families identified those with superior yield and quality traits, offer opportunitiesfor development of new varieties that may be of high value in food industry. Also the high linolenic acid and high oil content families recognized may have genetic potentials for development of new varieties of linseed for industrial purposes. Among the parental genotypes four were found to be promising for developing superior high yielding linseeds with high quality.
Effects of triglycidyl isocyanurate on thermal, mechanical, and gas barrier properties of poly(butylene adipate‐co‐terephthalate)/poly(propylene carbonate) composites
Authors: Xie Dong , Pang Qiyao , Zhao Yang , Li Yuan , Li Fayong , He Hui
Published: August 2022

The gas barrier properties of poly(butylene adipate‐co‐terephthalate) (PBAT) films can be improved with poly(propylene carbonate) (PPC), but this will reduce the mechanical properties. In this work, PBAT/PPC composites and the related films were prepared by melt blending followed by film blowing process using triglycidyl isocyanurate (TGIC) as the reactive compatibilizer. Herein, the structure, thermal properties, mechanical properties, and gas barrier properties of the composites were systematically characterized via various techniques. The results indicated that the incorporation of TGIC effectively improved the interfacial compatibility between PBAT and PPC, and enhanced the thermal stability of the composites, especially for PPC. In addition, PBAT/PPC/TGIC films at 1 phr (parts per hundreds of resin) TGIC content exhibited a tensile strength of 30.8 MPa, and an elongation at break of 860%, which are 136% and 142% of those of PBAT/PPC, respectively. Meanwhile, the water vapor transmission rate dropped by 33% at this content. The improvement of mechanics and gas barrier properties makes PBAT/PPC film better meet the requirements of food preservation packaging such as fruits and vegetables.
Technology follows Construction – Potenziale von Lowtech‐Gebäuden
Authors: Senkel Carolin , Otto Jens
Published: August 2022

Moderne energieeffiziente Gebäude definieren sich über einen hohen Grad an verbauter Technik. Durch deren vielseitigen Einsatz werden solche Gebäude als komfortabel und qualitativ hochwertiger empfunden. Auch die gesetzlichen Vorgaben und Förderungen lenken den Trend zukünftiger Gebäude hin zu einem hohen Grad energieeffizienter Technik. Dabei gilt jedoch der Leitsatz: Die beste Energie ist die, die erst gar nicht verbraucht wird. Um vor allem auch der grauen Energie Rechnung zu tragen und tatsächlich nachhaltige, zukunftsfähige Gebäude entstehen zu lassen, sollte ein Paradigmenwechsel eingeleitet werden hin zur Suffizienz. Ein Trend ist dabei besonders hervorzuheben – die Lowtech‐Gebäude. Sie folgen dem Grundsatz, zuerst die Potenziale der Baukonstruktion bauphysikalisch voll auszuschöpfen und danach die benötigte Restenergie durch Technik zu ergänzen. Definiert werden könnten sie durch den Leitsatz: Technology follows Construction. Lowtech‐Gebäude sind aber nicht nur im Kontext des Klimawandels vorteilhaft, sie bieten außerdem wirtschaftliche Lösungsansätze für Herausforderungen wie die gesellschaftliche Akzeptanz energieeffizienter Maßnahmen, die soziale Nachhaltigkeit und die Post‐Pandemie. Dank der zunehmenden Anzahl erfolgreicher Praxisprojekte gewinnen Lowtech‐Gebäude an Bedeutung.
Messtechnische Untersuchung der Auswirkung von Fassadenbegrünungen auf den U‐Wert der Außenwand
Authors: Alsaad Hayder , Engelhardt Miriam , Völker Conrad
Published: August 2022

Die kühlende Wirkung von Fassadenbegrünung wird in der Literatur häufig als ein Ansatz zur Bekämpfung des Klimawandels und der erhöhten Temperaturen im Sommer diskutiert. Neben diesem Effekt können Fassadenbegrünungen auch im Winter eine Dämmwirkung entfalten. In dieser Studie wurden die Auswirkungen eines Fassadenbegrünungsmoduls auf den Wärmetransport durch die dahinter stehende Außenwand während der Heizperiode untersucht. Dafür wurden empirische Messungen an einem Prototyp eines Begrünungsmoduls an einem Testcontainer durchgeführt. Zu den gemessenen Parametern gehörten die Oberflächen‐ und Lufttemperatur (jeweils innen und außen) und die Wärmestromdichte durch den Wandaufbau. Die Messungen wurden an zwei verschiedenen Stellen durchgeführt: ohne Begrünung (Referenzwand) und mit Begrünung. Der Wärmedurchgangskoeffizient der Fassade wurde für beide Stellen nach drei verschiedenen Datenfilterungsmethoden berechnet. Die Ergebnisse zeigen, dass das Fassadenbegrünungsmodul den Wärmetransport durch die Wand reduziert. Je nach verwendeter Filterungsmethode ergibt sich durch die Fassadenbegrünung eine Reduktion des Wärmedurchgangskoeffizienten des Wandaufbaus um 9 % bis 18 %.
Einsatz von Computerprogrammen in der Hochschullehre– Serie: Gebäudesimulation und Berechnungstools in der Lehre
Authors: Voss Karsten , Kalpkirmaz Rizaoglu Isil
Published: August 2022

Diese Artikelserie stellt den Einsatz von Computerprogrammen in der Hochschullehre der Bauphysik und Gebäudetechnik für Architekten und Bauingenieure vor.

In diesem Beitrag werden die Motivation zur Artikelserie und die Ergebnisse einer Online‐Umfrage an die Lehrenden der deutschsprachigen Hochschulen, initiiert und durchgeführt vom Fachgebiet Bauphysik und Technische Gebäudeausrüstung der Universität Wuppertal, aufgeführt.
Variable selection for nonparametric additive Cox model with interval‐censored data
Authors: Tian Tian , Sun Jianguo
Published: August 2022

The standard Cox model is perhaps the most commonly used model for regression analysis of failure time data but it has some limitations such as the assumption on linear covariate effects. To relax this, the nonparametric additive Cox model, which allows for nonlinear covariate effects, is often employed, and this paper will discuss variable selection and structure estimation for this general model. For the problem, we propose a penalized sieve maximum likelihood approach with the use of Bernstein polynomials approximation and group penalization. To implement the proposed method, an efficient group coordinate descent algorithm is developed and can be easily carried out for both low‐ and high‐dimensional scenarios. Furthermore, a simulation study is performed to assess the performance of the presented approach and suggests that it works well in practice. The proposed method is applied to an Alzheimer's disease study for identifying important and relevant genetic factors.
Multimodular vascularized bone construct comprised of vasculogenic and osteogenic microtissues
Authors: Schott Nicholas G. , Vu Huy , Stegemann Jan P.
Published: August 2022

Bioengineered bone designed to heal large defects requires concomitant development of osseous and vascular tissue to ensure engraftment and survival. Adult human mesenchymal stromal cells (MSC) are promising in this application because they have demonstrated both osteogenic and vasculogenic potential. This study employed a modular approach in which cells were encapsulated in biomaterial carriers (microtissues) designed to support tissue‐specific function. Osteogenic microtissues consisting of MSC embedded in a collagen‐chitosan matrix; vasculogenic (VAS) microtissues consisted of endothelial cells and MSC in a fibrin matrix. Microtissues were precultured under differentiation conditions to induce appropriate MSC lineage commitment, and were then combined in a surrounding fibrin hydrogel to create a multimodular construct. Results demonstrated the ability of microtissues to support lineage commitment, and that preculture primes the microtissues for the desired function. Combination of osteogenic and vasculogenic microtissues into multimodular constructs demonstrated that osteogenic priming resulted in sustained osteogenic activity even when cultured in vasculogenic medium, and that vasculogenic priming induced a pericyte‐like phenotype that resulted in development of a primitive vessel network in the constructs. The modular approach allows microtissues to be separately precultured to harness the dual differentiation potential of MSC to support both bone and blood vessel formation in a unified construct.
Fabrication and in vitro evaluation of 3D printed porous silicate substituted calcium phosphate scaffolds for bone tissue engineering
Authors: Chen Dechun , Chen Guanghua , Zhang Xin , Chen Jingtao , Li Jinmeng , Kang Kunlong , He Weitao , Kong Yuanhang , Wu Leilei , Su Bo , Zhao Kui , Si Daiwei , Wang Xintao
Published: August 2022

Silicate‐substituted calcium phosphate (Si‐CaP) ceramics, alternative materials for autogenous bone grafting, exhibit excellent osteoinductivity, osteoconductivity, biocompatibility, and biodegradability; thus, they have been widely used for treating bone defects. However, the limited control over the spatial structure and weak mechanical properties of conventional Si‐CaP ceramics hinder their wide application. Here, we used digital light processing (DLP) printing technology to fabricate a novel porous 3D printed Si‐CaP scaffold to enhance the scaffold properties. Scanning electron microscopy, compression tests, and computational fluid dynamics simulations of the 3D printed Si‐CaP scaffolds revealed a uniform spatial structure, appropriate mechanical properties, and effective interior permeability. Furthermore, compared to Si‐CaP groups, 3D printed Si‐CaP groups exhibited sustained release of silicon (Si), calcium (Ca), and phosphorus (P) ions. Furthermore, 3D printed Si‐CaP groups had more comprehensive and persistent osteogenic effects due to increased osteogenic factor expression and calcium deposition. Our results show that the 3D printed Si‐CaP scaffold successfully improved bone marrow mesenchymal stem cells (BMSCs) adhesion, proliferation, and osteogenic differentiation and possessed a distinct apatite mineralization ability. Overall, with the help of DLP printing technology, Si‐CaP ceramic materials facilitate the fabrication of ideal bone tissue engineering scaffolds with essential elements, providing a promising approach for bone regeneration.
Rapid Identification of Polypeptide from Carbapenem‐Resistant and SusceptibleEscherichia colivia Orbitrap‐MS and Pattern Recognition Analyses
Authors: Sun Bing‐Kang , Wang Rui‐Yu , Li Bei , Fan Xing , Zhou Yuan , Gu Bing , Yan Yang‐Yang
Published: August 2022

A rapid and accurate analytical method was established to identify CREC and CSEC. Orbitrap‐MS was used to detect the polypeptide of CREC and CSEC strains, and MS data were analyzed by pattern recognition analyses such as hierarchical cluster analysis (HCA), principal component analysis (PCA), partial least squares discriminant analysis (PLS‐DA), and orthogonal partial least squares discriminant analysis (OPLS‐DA). HCA based on the farthest distance method could well distinguish the two types ofE. coli, and the cophenetic correlation coefficient of the farthest distance method was 0.901. Comparing the results of PCA, PLS‐DA, and OPLS‐DA, OPLS‐DA exhibited the highest accuracy in predicting the CREC and CSEC strains. A total of 26 compounds were identified, and six of the compounds were the highly significant difference between the two types of strains. MS combined with pattern recognition can achieve a more comprehensive and efficient statistical analysis of complex biological samples.
Polycaprolactone‐co‐polylactic acid nanofiber scaffold in combination with 5‐azacytidine and transforming growth factor‐β to induce cardiomyocyte differentiation of adipose‐derived mesenchymal stem cells
Authors: Tambrchi Parastoo , Mahdavi Amir Hossein , DaliriJoupari Morteza , Soltani Leila
Published: August 2022

Adipose‐derived mesenchymal stem cells (Ad‐MSCs) are promising candidates for cardiac repair/regeneration. The application of copolymer nanoscaffolds has received great attention in tissue engineering to support differentiation and functional tissue organization toward effective tissue regeneration. The objective of the current study was to develop functional and bioactive scaffolds by combining polycaprolactone (PCL) and polylactic acid (PLA) for cardiomyocyte differentiation of human Ad‐MSC (hAd‐MSCs) in the absence or presence of 5‐azacytidine and transforming growth factor‐β (TGF‐β). To that end, the human MSCs were extracted from human adipose tissue (AD). The cardiomyocyte differentiation potency of hAd‐MSCs was evaluated on the novel synthetic PCL/PLA nanofiber scaffolds prepared in the absence and presence of 5‐azacytidine and TGF‐β supplements. A PCL/PLA nanofibrous scaffold was fabricated using the electrospinning method and its nanotopography and porous structure were characterized using scanning electron microscopy. In addition, the attachment of hAd‐MSCs on the PCL/PLA scaffolds was semiquantitatively investigated. Compared with other treatments, the PCL/PLA nanofibrous scaffold supplemented with both 5‐azacytidine and TGF‐β was observed to differentiate hAd‐MSCs into cardiomyocytes at Day 21 as evidenced by real‐time PCR for cardiac‐specific genes including cardiac troponin I (cTnI), GATA4, MYH7, and NKX2.5. In addition, flow cytometric analysis of cTnI‐positive cells demonstrated that the cardiomyocyte differentiation of hAd‐MSCs was more efficient on the PCL/PLA nanofibrous scaffold supplemented with both 5‐azacytidine and TGF‐β than it was in the other treatment groups. Generally speaking, the results show that PCL/PLA nanofibrous scaffolds may be applied as a platform for efficient differentiation of hAd‐MSCs into functional cardiomyocytes.
High bone mass in mice can be linked to lower osteoclast formation, resorptive capacity, and restricted in vitro sensitivity to inhibition by stable sulforaphane
Authors: Louka Polymnia , Orriss Isabel R. , Pitsillides Andrew A.
Published: August 2022

Mouse strains can have divergent basal bone mass, yet this phenotype is seldom reflected in the design of studies seeking to identify new modulators of bone resorption by osteoclasts. Sulforaphane exerts inhibitory effects on in vitro osteoclastogenesis in cells from C57BL/6 mice. Here, we explore whether a divergent basal bone mass in different mouse strains is linked both to in vitro osteoclastogenic potential and to SFX‐01 sensitivity. Accordingly, osteoclasts isolated from the bone marrow (BM) of C57BL/6, STR/Ort and CBA mice with low, high, and intermediate bone mass, respectively, were cultured under conditions to promote osteoclast differentiation and resorption; they were also treated with chemically stabilised sulforaphane (SFX‐01) and respective sensitivity to inhibition evaluated by counting osteoclast number/resorption activity on dentine discs. We observed that osteoclastogenesis exhibited different macrophage colony‐stimulating factor/receptor activator of nuclear factor kappa‐Β ligand sensitivity in these mouse strains, with cells from C57BL/6 and CBA generating higher osteoclast numbers than STR/Ort; the latter formed only half as many mature osteoclasts. We found that 100 nM SFX‐01 exerted a potent and significant reduction in osteoclast number and resorptive activity in cells derived from C57BL/6 mice. In contrast, 10‐fold higher SFX‐01 concentrations were required for similar inhibition in CBA‐derived cells and, strikingly, a further 2.5‐fold greater concentration was required for significant restriction of osteoclast formation/function in STR/Ort. These data are consistent with the notion that the BM osteoclast precursor population contributes to the relative differences in mouse bone mass and that mice with higher bone mass exhibit lower in vitro osteoclastogenic potential as well as reduced sensitivity to inhibition by SFX‐01.
Ruthenium(II) Polypyridyl Complexes Containing Simple Dioxo Ligands: a Structure‐Activity Relationship Study Shows the Importance of the Charge
Authors: Gandioso Albert , Vidal Alessio , Burckel Pierre , Gasser Gilles , Alessio Enzo
Published: August 2022

Cancer is one of the main causes of death worldwide. Platinum complexes (i. e., cisplatin, carboplatin, and others) are currently heavily used for the treatment of different types of cancer, but unwanted effects occur. Ruthenium complexes have been shown to be potential promising alternatives to these metal‐based drugs. In this work, we performed a structure‐activity relationship (SAR) study on two small series of Ru(II) polypyridyl complexes of the type [Ru(L1)2(O^O)]Cln (3–8), where L1 is 4,7‐diphenyl‐1,10‐phenantroline (DIP) or 1,10‐phenantroline (phen), and O^O is a symmetrical anionic dioxo ligand: oxalate (ox, n=0), malonate (mal, n=0), or acetylacetonate (acac, n=1). These two self‐consistent series of compounds allowed us to perform a systematic investigation for establishing how the nature of the ligands and the charge affect the anticancer properties of the complexes. Cytotoxicity tests on different cell lines demonstrated that some of the six compounds 3–8 have a promising anticancer activity. More specifically, the cationic complex [Ru(DIP)2(η2‐acac)]Cl (4) has IC50 values in the mid‐nanomolar concentration range, lower than those of cisplatin on the same cell lines. Interestingly, [Ru(DIP)2(η2‐acac)]Cl was found to localize mainly in the mitochondria, whereas a smaller fraction was detected in the nucleus. Overall, our SAR investigation demonstrates the importance of combining the positive charge of the complex with the highly lipophilic diimine ligand DIP.
Chaperone‐mediated autophagy attenuates H2O2‐induced cardiomyocyte apoptosis by targeting poly (ADP‐ribose) polymerase 1 (PARP1) for lysosomal degradation
Authors: Zhang Dandan , Lai Wei , Liu Yang , Wan Rong , Shen Yang
Published: August 2022

Poly (ADP‐ribose) polymerase 1 (PARP1) is a typical representative of the PARP enzyme family and is mainly related to DNA repair, gene transcription regulation, inflammation, and oxidative stress. Studies have found that PARP1 is involved in the pathophysiological processes of a variety of cardiovascular diseases. Chaperone‐mediated autophagy (CMA) is involved in the molecular regulation of various diseases, including cardiovascular diseases, and plays a critical role in maintaining intracellular metabolism balance. However, the link between PARP1 and CMA in cardiomyocytes remains unclear. Therefore, the aims of this study were to investigate whether CMA is involved in PARP1 regulation and to further clarify the specific molecular mechanisms. Earle's balanced salt solution (EBSS)‐induced activation of autophagy reduced PARP1 expression, whereas the autophagy lysosomal inhibitor CQ had the opposite effect. Correspondingly, treatment with the autophagy inhibitor 3‐methyladenine did not abolish the autophagy‐inducing effects of EBSS. Additionally, PARP1 binds to heat shock cognate protein 70 and lysosome‐associated membrane protein 2A (LAMP2A). Moreover, adenovirus‐mediated LAMP2A overexpression to activate the CMA signaling pathway in cardiomyocytes reduces PARP1 (cleaved) expression and further decreases cardiomyocyte apoptosis caused by oxidative stress. In contrast, downregulation of LAMP2A increased PARP1 (cleaved) expression and the degree of apoptosis. More importantly, we report that appropriate concentrations of H2O2 triggered the nuclear translocation of PARP1, which subsequently promoted the degradation of PARP1 through the CMA pathway. In summary, our data are the first to reveal that CMA targeted PARP1 for lysosomal degradation in cardiomyocytes, which ultimately inhibited apoptosis by promoting the degradation of the PARP1 protein.
Annealing Treatment: A Facile Approach to Enhance Transfer Kinetics for a LiFePO4/C Cathode
Authors: Yang Maoping , Jia Xueying , Li Pengfei , Yao Jie , Wang Weiwei
Published: August 2022

Nowadays, solid phase synthesis has been proven to be the most cost‐effective and convenient approach to mass preparation of a LiFePO4/C cathode. Nevertheless, the LiFePO4/C cathode usually shows unsatisfactory electrochemical performance due to its high proportion of antisite defects and inefficient carbon coating. In this work, a post‐synthesis annealing treatment method is used to improve the ionic and electron transfer kinetics of high‐temperature solid phase synthesized LiFePO4/C. Owing to the annealing treatment, the proportion of Fe‐Li antisite defects in the LiFePO4 crystal can be significantly reduced. The graphitization degree of carbon coating on LiFePO4 has been increased. This contributes to the enhancement of rapid transfer kinetics and suppressed polarization of the electrode.
A Quick and Reproducible Silanization Method by Using Plasma Activation for Hydrophobicity‐Based Kinesin Single Molecule Fluorescence–Microscopy Assays
Authors: Wedler Viktoria , Quinones Dustin , Peisert Heiko , Schäffer Erik
Published: August 2022

Single‐molecule assays often require functionalized surfaces. One approach for microtubule assays renders surfaces hydrophobic and uses amphiphilic blocking agents. However, the optimal hydrophobicity is unclear, protocols take long, produce toxic waste, and are susceptible to failure. Our method uses plasma activation with hydrocarbons for hexamethyldisilazane (HMDS) silanization in the gas phase. We measured the surface hydrophobicity, its effect on how well microtubule filaments were bound to the surface, and the number of nonspecific interactions with kinesin motor proteins. Additionally, we tested and discuss the use of different silanes and activation methods. We found that even weakly hydrophobic surfaces were optimal. Our environmentally friendly method significanty reduced the overall preparation effort and resulted in reproducible, high‐quality surfaces with low variability. We expect the method to be applicable to a wide range of other single‐molecule assays.
Molecularly Imprinted Nanozymes with Free Substrate Access for Catalyzing the Ligation of ssDNA Sequences
Authors: Guo Zhanchen , Luo Qi , Liu Zhen
Published: August 2022

Nanozymes have attracted wide attention for the unique advantages of low cost, high stability and designability. Molecularly imprinted polymers (MIPs) have demonstrated great potential as a new type of nanozymes due to their excellent specificity and high affinity. However, effective approaches for creating molecularly imprinted nanozymes still remain limited. Herein, reverse microemulsion template docking surface imprinting (RMTD‐SI) is reported as a new approach for the rational design and engineering of nanozymes with free substrate access for the ligation of ssDNA sequences. As a proof of the principle, octa‐deoxyribonucleotide‐imprinted nanoparticles were successfully prepared. Using tetradeoxyribonucleotides and octa‐deoxyribonucleotide as substrates, the properties, catalytic activity and behavior of the imprinted nanoparticles were thoroughly investigated. The imprinted nanozyme exhibited an enhanced reaction speed (by up to 41‐fold) and good sequence selectivity towards substrate tetra‐deoxyribonucleotides. More interestingly, due to the open substrate access, the imprinted nanozyme also allowed the ligation of a ssDNA that fully matched with the imprinted cavity and other ssDNA substrates to form longer sequences, but at the price of substrate selectivity. Thus, this study provides not only a new avenue to the rational design and synthesis of molecularly imprinted nanozymes but also new insights of their catalytic behavior.
Estimation of SARS‐CoV‐2 antibody prevalence through serological uncertainty and daily incidence
Authors: Wang Liangliang , Min Joosung , Doig Renny , Elliott Lloyd T. , Colijn Caroline
Published: August 2022

Serology tests for SARS‐CoV‐2 provide a paradigm for estimating the number of individuals who have had an infection in the past (including cases that are not detected by routine testing, which has varied over the course of the pandemic and between jurisdictions). Such estimation is challenging in cases for which we only have limited serological data and do not take into account the uncertainty of the serology test. In this work, we provide a joint Bayesian model to improve the estimation of the sero‐prevalence (the proportion of the population with SARS‐CoV‐2 antibodies) through integrating multiple sources of data, priors on the sensitivity and specificity of the serological test, and an effective epidemiological dynamics model. We apply our model to the Greater Vancouver area, British Columbia, Canada, with data acquired during the pandemic from the end of January to May 2020. Our estimated sero‐prevalence is consistent with previous literature but with a tighter credible interval.
Association of lipoprotein(a) with aortic dissection
Authors: Yang Yiheng , Hong Yuting , Yang Weihua , Zheng Zhenzhong
Published: August 2022

Background

Lipoprotein(a) [Lp(a)] is associated with coronary atherosclerotic heart disease, aortic stenosis, stroke, and heart failure. We aimed to determine the relationship between Lp(a) and aortic dissection (AD).

Methods

Two hundred patients with AD were included in our case group. The control group consisted of 200 non‐AD people who were age‐ (±5 years) and gender‐matched to the case group. Data were collected retrospectively, including hypertension, smoking, coronary artery disease, diabetes mellitus, Lp(a), total cholesterol, triglyceride, low‐density lipoprotein cholesterol, and high‐density lipoprotein cholesterol. The association between Lp(a) and AD was studied using univariate and multivariate logistic regression analysis.

Results

Patients with AD had greater median Lp(a) concentrations than non‐AD people (152.50 vs. 81.75 mg/L). Lp(a) was associated with AD in a multivariate logistic regression analysis (odds ratio, 8.03; 95% confidence interval, 2.85–22.62), comparing those with Lp(a) quartile 4 with those with Lp(a) quartile 1. Stratified analysis showed that this relationship was observed in both men and women, as well as in older and younger individuals.

Conclusions

High levels of Lp(a) are strongly associated with AD, independent of other cardiovascular risk factors.
QM/MM Study of the Reaction Mechanism of Thermophilic Glucuronoyl Esterase for Biomass Treatment
Authors: Viegas Matilde F. , Neves Rui P. P. , Ramos Maria J. , Fernandes Pedro A.
Published: August 2022

Hydrolysis of lignocellulosic biomass, composed of a lignin‐carbohydrate‐complex (LCC) matrix, is critical for producing bioethanol from glucose. However, current methods for LCC processing require costly and polluting processes. The fungal Thermothelomyces thermophila glucuronoyl esterase (TtGE) is a promising thermophilic enzyme that hydrolyses LCC ester bonds. This study describes the TtGE catalytic mechanism using QM/MM methods. Two nearly‐degenerate rate‐determining transition states were found, with barriers of 16 and 17 kcal ⋅ mol−1, both with a zwitterionic nature that results from a proton interplay from His346 to either the Ser213‐hydroxyl or the lignin leaving group and the rehybridisation of the ester moiety of the substrate to an alkoxide. An oxyanion hole, characteristic of esterases, was provided by the conserved Arg214 through its backbone and sidechain. Our work further suggests that a mutation of Glu267 to a non‐negative residue will decrease the energetic barrier in ca. −5 kcal ⋅ mol−1, improving the catalytic rate of TtGE.
Formation of silicone thin films by ArF excimer laser induced photo‐desorption
Authors: Okoshi Masayuki
Published: August 2022

Low molecular weight silicones were ejected from silicone rubber target irradiated by a 193 nm ArF excimer laser through the photo‐desorption. The ejected silicones were successfully deposited on a fused silica glass substrate in air. An approximately 0.3 mm of the target‐substrate distance was required for the deposition. The deposited silicones became a thin film, showing an interference color when the ArF excimer laser was irradiated for a long time. Chemical bonding state of the formed thin films was analyzed by the Fourier transform infrared spectroscopy. The thin films were slightly different from the original silicone rubber structure, still it was composed of Si‐O‐Si bonds and Si‐CH3 bonds. Also, OH bonds were clearly produced in the silicone thin films. As a result, contact angle of water on the silicone thin films was measured to be approximately 20 degrees, indicating a hydrophilic property.
Cationic Nickel d9‐Metalloradicals [Ni(NHC)2]+
Authors: Tendera Lukas , Luff Martin S. , Krummenacher Ivo , Radius Udo
Published: August 2022

A series of five new homoleptic, linear nickel d9‐complexes of the type [NiI(NHC)2]+ is reported. Starting from the literature known Ni(0) complexes [Ni(Mes2Im)2] 1, [Ni(Mes2ImH2)2] 2, [Ni(Dipp2Im)2] 3, [Ni(Dipp2ImH2)2] 4 and [Ni(cAACMe)2] 5 (Mes2Im=1,3‐bis(2,4,6‐trimethylphenyl)‐imidazolin‐2‐ylidene, Mes2ImH2=1,3‐bis(2,4,6‐trimethylphenyl)‐imidazolidin‐2‐ylidene, Dipp2Im=1,3‐bis(2,6‐diisopropylphenyl)‐imidazolin‐2‐ylidene, Dipp2ImH2=1,3‐bis(2,6‐diisopropylphenyl)‐imidazolidin‐2‐ylidene, cAACMe=1‐(2,6‐diisopropylphenyl)‐3,3,5,5‐tetramethylpyrrolidin‐2‐yliden), their oxidized Ni(I) analogues [NiI(Mes2Im)2][BPh4] 1+, [NiI(Mes2ImH2)2][BPh4] 2+, [NiI(Dipp2Im)2][BPh4] 3+, [NiI(Dipp2ImH2)2][BPh4] 4+ and [NiI(cAACMe)2][BPh4] 5+ were synthesized by one‐electron oxidation with ferrocenium tetraphenyl‐borate. The complexes 1+–5+ were fully characterized including X‐ray structure analysis. The complex cations reveal linear geometries in the solid state and NMR spectra with extremely broad, paramagnetically shifted resonances. DFT calculations predicted an orbitally degenerate ground state leading to large magnetic anisotropy, which was verified by EPR measurements in solution and on solid samples. The magnetic anisotropy of the complexes is highly dependent from the steric protection of the metal atom, which results in a noticeable decrease of the g‐tensor anisotropy for the N‐Mes substituted complexes 1+ and 2+ in solution due to the formation of T‐shaped THF adducts.
Homo bodoensis and why it matters
Authors: Roksandic Mirjana , Radović Predrag , Wu Xiu‐Jie , Bae Christopher J.
Published: August 2022

In our original paper, we proposed a new species, Homo bodoensis, to replace the problematical taxa Homo heidelbergensis and Homo rhodesiensis, with the goal of streamlining communication about human evolution in the Chibanian. We received two independent responses. Given their substantial overlap, we provide one combined reply. In this response: (1) we are encouraged that the primary proposal in our paper, to discontinue the use of H. heidelbergensis (as a junior synonym to Homo neanderthalensis) due to its' nomenclatural problems, is acknowledged. (2) we provide additional clarification about the rules governing taxonomic nomenclature as outlined by the International Code of Zoological Nomenclature and join the growing calls for a revision to these rules. (3) we discuss further why H. rhodesiensis should be abandoned, particularly in light of the current sensitivity to using culturally inappropriate names. We conclude that H. bodoensis is a better solution than the proposed alternatives.
Piecewise linear boundary crossing probabilities, barrier options, and variable annuities
Authors: Lee Hangsuck , Ha Hongjun , Lee Minha
Published: August 2022

Barrier options have been instrumental in satisfying various market demands. This paper introduces piecewise linear barrier options and provides their pricing formulas. To this end, we establish the analytical piecewise linear boundary crossing probability and explain how to approximate arbitrary boundary crossing probabilities. In addition, we show that a financial instrument with early exercise is decomposable into a knock‐out barrier option and immediate rebate, which casts a new illumination of the value of early exercise. We consider a variable annuity with guaranteed minimum accumulation benefit rider and surrender option to illustrate the decomposition. Extensive numerical experiments validate theoretical findings.
Forecasting realized volatility: New evidence from time‐varying jumps in VIX
Authors: Dutta Anupam , Das Debojyoti
Published: August 2022

Given that jumps in the implied volatility index (VIX) lead to rapid changes in the level of volatility, they may contain significant predictive information for the realized variance (RV) of stock returns. Against this backdrop, the present study proposes to extend the heterogeneous autoregressive (HAR) model using the information content of time‐varying jumps occurring in VIX. We find that jumps in VIX have positive impacts on the RV of S&P 500 index and that the proposed HAR‐RV approach generates more accurate volatility forecasts than do the existing HAR‐RV type models. Importantly, these results hold for short‐, medium‐, and long‐term volatility components.
Genetic heterogeneity: Challenges, impacts, and methods through an associative lens
Authors: Woodward Alexa A. , Urbanowicz Ryan J. , Naj Adam C. , Moore Jason H.
Published: August 2022

Genetic heterogeneity describes the occurrence of the same or similar phenotypes through different genetic mechanisms in different individuals. Robustly characterizing and accounting for genetic heterogeneity is crucial to pursuing the goals of precision medicine, for discovering novel disease biomarkers, and for identifying targets for treatments. Failure to account for genetic heterogeneity may lead to missed associations and incorrect inferences. Thus, it is critical to review the impact of genetic heterogeneity on the design and analysis of population level genetic studies, aspects that are often overlooked in the literature. In this review, we first contextualize our approach to genetic heterogeneity by proposing a high‐level categorization of heterogeneity into “feature,” “outcome,” and “associative” heterogeneity, drawing on perspectives from epidemiology and machine learning to illustrate distinctions between them. We highlight the unique nature of genetic heterogeneity as a heterogeneous pattern of association that warrants specific methodological considerations. We then focus on the challenges that preclude effective detection and characterization of genetic heterogeneity across a variety of epidemiological contexts. Finally, we discuss systems heterogeneity as an integrated approach to using genetic and other high‐dimensional multi‐omic data in complex disease research.