bluuebunny/crossref_metadata_2025 huggingface dataset:
TBX1 targets the miR-200–ZEB2 axis to induce epithelial differentiation and inhibit stem cell properties
Authors: Funato Noriko , Yanagisawa Hiromi
Published: November 2022

TBX1, which encodes a T-box transcription factor, is considered a candidate gene for DiGeorge syndrome, velocardiofacial syndrome, and conotruncal anomaly face syndrome. Transduction of TBX1 decreases cell proliferation in epithelial cancer cells and Tbx1 ablation induces epithelial proliferation during palatal development. Here, we report that TBX1 regulates stem cell properties and epithelial differentiation through the transcriptional activation of microRNAs. Stable expression of TBX1 induces microRNA-200 (miR-200), whose members repress the epithelial-to-mesenchymal transition and induce epithelial differentiation. TBX1 rescues ZEB2-dependent transcriptional inhibition of the miR-200b/200a/429 cluster, whose promoter region contains conserved overlapping cis-regulatory motifs of the ZEB-binding E-box and TBX-binding element. Consequently, TBX1 activates the expression of both miR-200 and stemness-inhibitor miR-203 to inhibit their common targets, BMI1 and ZEB2. Moreover, Tbx1 ablation affects the differentiation of the palatal epithelium and perturbs the expression of miR-200, miR-203, and their target genes. We propose that TBX1 links stem cell properties and epithelial differentiation by inducing miR-200 and miR-203. Thus, targeting of the ZEB2–miR-200 axis by TBX1 may have potential therapeutic implications in miR-200-associated tumors and cleft palate.
Effective degradation of organophosphate ester flame retardants and plasticizers in coastal sediments under high urban pressure
Authors: Castro-Jiménez J. , Cuny P. , Militon C. , Sylvi L. , Royer F. , Papillon L. , Sempéré R.
Published: November 2022

Empirical evidence of the effective degradation at environmentally relevant conditions of organophosphate esters (OPEs) flame retardants and plasticizers in coastal sediments from an impacted area in the NW Mediterranean Sea is provided. Half-lives varied from 23.3 to 77.0 (abiotic conditions) and from 16.8 to 46.8 days (biotic conditions), depending on the compound, highlighting the relevant role of microbial assemblages enhancing OPE degradation. After an immediate significant reduction of the bacterial abundance due to OPE addition to the sediment at the very beginning of the experiment, the observed biodegradation was associated to a general stimulation of the growth of the bacterial community during a first period, but without a marked change of the structure of the community. However, OPE contamination induced a decrease on the diversity of the bacterial community in the coastal sediment, noticeable after 14 days of incubation. It is likely that on one side the contamination had favoured the growth of some bacterial groups maybe involved in the biodegradation of these compounds but, on the other side, had also impacted some sensitive bacteria. The estimated half-lives fill a data gap concerning OPE degradation rates in marine sediments and will be valuable data for the refinement of OPE chemical risk assessment in marine environments, particularly on impacted sites.
MEK inhibitor resistance in lung adenocarcinoma is associated with addiction to sustained ERK suppression
Authors: Farnsworth Dylan A. , Inoue Yusuke , Johnson Fraser D. , de Rappard-Yuswack Georgia , Lu Daniel , Shi Rocky , Ma Lok In Josephine , Mattar Marissa S. , Somwar Romel , Ladanyi Marc , Unni Arun M. , Lockwood William W.
Published: November 2022

MEK inhibitors (MEKi) have limited efficacy in KRAS mutant lung adenocarcinoma (LUAD) patients, and this is attributed to both intrinsic and adaptive mechanisms of drug resistance. While many studies have focused on the former, there remains a dearth of data regarding acquired resistance to MEKi in LUAD. We established trametinib-resistant KRAS mutant LUAD cells through dose escalation and performed targeted MSK-IMPACT sequencing to identify drivers of MEKi resistance. Comparing resistant cells to their sensitive counterparts revealed alteration of genes associated with trametinib response. We describe a state of “drug addiction” in resistant cases where cells are dependent on continuous culture in trametinib for survival. We show that dependence on ERK2 suppression underlies this phenomenon and that trametinib removal hyperactivates ERK, resulting in ER stress and apoptosis. Amplification of KRASG12C occurs in drug-addicted cells and blocking mutant-specific activity with AMG 510 rescues the lethality associated with trametinib withdrawal. Furthermore, we show that increased KRASG12C expression is lethal to other KRAS mutant LUAD cells, consequential to ERK hyperactivation. Our study determines the drug-addicted phenotype in lung cancer is associated with KRAS amplification and demonstrates that toxic acquired genetic changes can develop de novo in the background of MAPK suppression with MEK inhibitors. We suggest that the presence of mutant KRAS amplification in patients may identify those that may benefit from a “drug holiday” to circumvent drug resistance. These findings demonstrate the toxic potential of hyperactive ERK signaling and highlight potential therapeutic opportunities in patients bearing KRAS mutations.
Co-targeting KRAS G12C and EGFR reduces both mutant and wild-type RAS-GTP
Authors: McFall Thomas , Trogdon Michael , Guizar Anita C. , Langenheim John F. , Sisk-Hackworth Laura , Stites Edward C.
Published: November 2022

The combination of KRAS G12C inhibitors with EGFR inhibitors has reproducibly been shown to be beneficial. Here, we identify another benefit of this combination: it effectively inhibits both wild-type and mutant RAS. We believe that targeting both mutant and wild-type RAS helps explain why this combination of inhibitors is effective.
High-refractive index and mechanically cleavable non-van der Waals InGaS3
Authors: Toksumakov Adilet N. , Ermolaev Georgy A. , Slavich Aleksandr S. , Doroshina Natalia V. , Sukhanova Ekaterina V. , Yakubovsky Dmitry I. , Syuy Alexander V. , Novikov Sergey M. , Romanov Roman I. , Markeev Andrey M. , Oreshonkov Aleksandr S. , Tsymbarenko Dmitry M. , Popov Zakhar I. , Kvashnin Dmitry G. , Vyshnevyy Andrey A. , Arsenin Aleksey V. , Ghazaryan Davit A. , Volkov Valentyn S.
Published: November 2022

The growing family of two-dimensional crystals has been recognized as a promising platform for investigation of rich low-dimension physics and production of a variety of devices. Of particular interest are recently reported atomic sheets of non-van der Waals materials, which reshape our understanding of chemical bonds and enable heterostructures with novel functionality. Here, we study the structural and optical properties of ultrathin non-van der Waals InGaS3 sheets produced by standard mechanical cleavage. Our ab initio calculations reveal weak out-of-plane covalent bonds, responsible for the layered structure of the material. The energy required for isolation of a single layer is as low as ~50 meVÅ–2, which is comparable with the conventional van der Waals material’s monolayer isolation energies of 20–60 meVÅ–2. A comprehensive study of the structural, vibrational, and optical properties of the material reveals its wide bandgap (2.73 eV), high refractive index (>2.5) and negligible losses in the visible and infrared spectral ranges. These properties make it a perfect candidate for visible-range all-dielectric nanophotonics.
Inhibition of VMAT2 by β2-adrenergic agonists, antagonists, and the atypical antipsychotic ziprasidone
Authors: Støve Svein Isungset , Skjevik Åge Aleksander , Teigen Knut , Martinez Aurora
Published: November 2022

Vesicular monoamine transporter 2 (VMAT2) is responsible for packing monoamine neurotransmitters into synaptic vesicles for storage and subsequent neurotransmission. VMAT2 inhibitors are approved for symptomatic treatment of tardive dyskinesia and Huntington’s chorea, but despite being much-studied inhibitors their exact binding site and mechanism behind binding and inhibition of monoamine transport are not known. Here we report the identification of several approved drugs, notably β2-adrenergic agonists salmeterol, vilanterol and formoterol, β2-adrenergic antagonist carvedilol and the atypical antipsychotic ziprasidone as inhibitors of rat VMAT2. Further, plausible binding modes of the established VMAT2 inhibitors reserpine and tetrabenazine and hit compounds salmeterol and ziprasidone were identified using molecular dynamics simulations and functional assays using VMAT2 wild-type and mutants. Our findings show VMAT2 as a potential off-target of treatments with several approved drugs in use today and can also provide important first steps in both drug repurposing and therapy development targeting VMAT2 function.
Antiviral supramolecular polymeric hydrogels by self-assembly of tenofovir-bearing peptide amphiphiles
Authors: Monroe Maya K. , Wang Han , Anderson Caleb F. , Qin Meng , Thio Chloe L. , Flexner Charles , Cui Honggang
Published: November 2022

Tenofovir-conjugated peptide amphiphiles can assemble and form hydrogels under physiological conditions for sustained therapeutic release. Varying the number of valines in the designs impacts their self-assembly, gelation, and release behavior.
Markovnikov-selective double hydrosilylation of challenging terminal aryl alkynes under cobalt and iron catalysis
Authors: Banach Łukasz , Brykczyńska Daria , Gorczyński Adam , Wyrzykiewicz Bożena , Skrodzki Maciej , Pawluć Piotr
Published: November 2022

Bench-stable complexes with a tridentate ligand serve as precatalysts in the synthesis of geminal bis(silanes) from terminal aryl alkynes regarded as challenging substrates in this transformation.
Na-doped g-C3N4/NiO 2D/2D laminated p–n heterojunction nanosheets toward optimized photocatalytic performance
Authors: Gao Jiapeng , Xing Zipeng , Liu Meijie , Wang Yichao , Zhang Na , Li Zhenzi , Chen Peng , Zhou Wei
Published: November 2022

Na-doped g-C3N4/NiO 2D/2D laminated p-n heterojunction nanosheets are successfully fabricated. The excellent photocatalytic performance is attributed to the large specific surface area, sufficient active sites and wide light absorption range.
Ecotoxicological effect of enrofloxacin on Spirulina platensis and the corresponding detoxification mechanism
Authors: Jiang Xiaohua , Wang Dabin , Wu Weiran , Li Fengmin
Published: November 2022

Spirulina platensis showed specific sensitivity and remediation capability towards the emerging pollutant enrofloxacin.
Electrochemical fabrication of mesoporous metal-alloy films
Authors: Bashir Javeria , Chowdhury Md. Belal , Kathak Rahanuma Raihanu , Dey Shuvashis , Tasnim Atiya Tahira , Amin Mohammed A. , Kaneti Yusuf Valentino , Masud Mostafa Kamal , Hossain Md. Shahriar A
Published: November 2022

Electrochemical fabrication integrating templating strategies have paved the way for creating mesoporous metal alloy films with distinctive pores and functionalities for electrocatalysis, fuel cells, and sensor (bio) development.
Fabrication and biological evaluation of three-dimensional (3D) Mg substituted bi-phasic calcium phosphate porous scaffolds for hard tissue engineering
Authors: Ramadas Munusamy , Abimanyu Ravichandran , Ferreira José M. F. , Ballamurugan Anbalagan M.
Published: November 2022

This work reports on the fabrication of three-dimensional (3D) magnesium substituted bi-phasic calcium phosphate (Mg–BCP) scaffolds by gel-casting, their structural and physico-chemical characterization, and on the assessment of their in vitro and in vivo performances.
Photo-controlled and photo-calibrated nanoparticle enabled nitric oxide release for anti-bacterial and anti-biofilm applications
Authors: Li Li , Lin Zhenmei , Lu Xicun , Chen Chen , Xie Anqi , Tang Yaoping , Zhang Ziqian
Published: November 2022

A photo-controlled and photo-calibrated NO-releasing nanoparticle has been developed, and its anti-bacteria effects are elucidated in this study.
Synthesis, combined theoretical and spectral characterization of some new 1,3,5 triazine compounds, and their in vitro biological analysis
Authors: Noureen Sadia , Ali Shaukat , Zia Muhammad Anjum , Afzal Muhammad , Ayub Ali Raza , El-Naggar Mohamed
Published: November 2022

New N-heterocyclic compounds with a 1,3,5 triazine core were synthesized by a nucleophilic substitution reaction.
Design rules for 2D field mediated assembly of different shaped colloids into diverse microstructures
Authors: Hendley Rachel S. , Zhang Lechuan , Bevan Michael A.
Published: November 2022

2D assembly of circular, square, elliptical, and rectangular prisms yields liquid, liquid crystalline, and crystalline states. Particle shape and field dependent states quantified using order parameters reveal design rules for 2D microstructures.
Tailoring the antibacterial and antioxidant activities of iron nanoparticles with amino benzoic acid
Authors: Faisal Shah , Sadiq Saima , Mustafa Muhammad , Khan Muhammad Hayat , Sadiq Muhammad , Iqbal Zaffar , Khan Maham
Published: November 2022

Antibacterial resistance is a massive universal health crisis and one of the most significant threats to human life. Many bacterial species have evolved and acquired resistance against multiple drugs.
Stacked vanadium pentoxide–zinc oxide interface for optically-chargeable supercapacitors
Authors: Chauhan Pankaj Singh , Kumar Sumana , Mondal Anindita , Sharma Pragya , Parekh Mihir N. , Panwar Vinod , Rao Apparao M. , Misra Abha
Published: November 2022

Photo-chargeable supercapacitor from a ZnO and V2O5 layered structure under UV illumination.
A water-induced self-assembly approach to 3D hierarchical magnetic MXene networks for enhanced microwave absorption
Authors: Xu Jian , Ma Wenjun , He Peng , Zhou Yukang , Liu Xiaoyun , Chen Yi , Zuo Peiyuan , Zhuang Qixin
Published: November 2022

A novel water-induced self-assembly method is developed for constructing ultrafine magnetic nanocrystal@carbon@MXene with continuous interfaces and high-density magnetic coupling networks.
Supramolecular catalytic nanomedicines based on coordination self-assembly of amino acids for cascade-activated and -amplified synergetic cancer therapy
Authors: Song Enhui , Wu Qiong , Gao Ren , Lan Xiaopeng , Zhang Yanhui , Geng Hao , Liu Chunlei , Xu Feijie , Li Yongxin , Liu Chunzhao
Published: November 2022

An amino acid based- supramolecular nanomedicine is constructed based on multicomponent coordination self-assembly for tumor cascade- activated and -amplified synergetic catalytic-chemotherapy, which achieved efficient tumor growth suppression.
Multi-state photochromism of bis-tetraarylethene luminogens modulated through oligosilane linkages
Authors: Zhou Chuanting , Zhou Zhikuan , Yu Fuhuan , Xie Wei , Zhang Wenjun , Yang Qiaomei , Xu Xiaodong , Gai Lizhi , Lu Hua
Published: November 2022

Controllable photochromic molecules both in solutions and solid states (amorphous, films, and crystals) are valuable nascent optical materials.
Rapid blue- and redshifted excursions in Hα line profiles synthesized from realistic 3D magnetohydrodynamic simulations
Authors: Danilovic S. , Bjørgen J. P. , Leenaarts J. , Rempel M.
Published: November 2022

Context. Rapid blue- and redshifted excursions (RBEs and RREs) may play an important role in mass-loading and heating the solar corona, but their nature and origin are still debatable.

Aims. We aim to model these features to learn more about their properties, formation, and origin.

Methods. We created a realistic three-dimensional (3D) magnetohydrodynamic model of a solar plage region. Synthetic Hα spectra were generated and the spectral signatures of these features identified. The magnetic field lines associated with these events were traced, and the underlying dynamic was studied.

Results. The model reproduces many properties of RBEs and RREs well, such as spatial distribution, lateral movement, length, and lifetimes. Synthetic Hα line profiles, similarly to observed ones, show a strong blue- or redshift as well as asymmetries. These line profiles are caused by the vertical component of velocities higher than 30 − 40 km s−1, which mostly appear in the height range 2 − 4 Mm. By tracing magnetic field lines, we show that the vertical velocity that causes the appearance of RBEs or RREs is always associated with the component of velocity perpendicular to the magnetic field lines.

Conclusions. The study confirms the hypothesis that RBEs and RREs are signs of Alfvénic waves with, in some cases, a significant contribution from slow magneto-acoustic modes.
Sulphur monoxide emission tracing an embedded planet in the HD 100546 protoplanetary disk
Authors: Booth Alice S. , Ilee John D. , Walsh Catherine , Kama Mihkel , Keyte Luke , van Dishoeck Ewine F. , Nomura Hideko
Published: November 2022

Molecular line observations are powerful tracers of the physical and chemical conditions across the different evolutionary stages of star, disk, and planet formation. The high angular resolution and unprecedented sensitivity of the Atacama Large Millimeter Array (ALMA) enables the current drive to detect small-scale gas structures in protoplanetary disks that can be attributed directly to forming planets. We report high angular resolution ALMA Band 7 observations of sulphur monoxide (SO) in the nearby planet-hosting disk around the Herbig star HD 100546. SO is rarely detected in evolved protoplanetary disks, but in other environments, it is most often used as a tracer of shocks. The SO emission from the HD 100546 disk primarily originates from gas within the ≈20 au millimeter-dust cavity and shows a clear azimuthal brightness asymmetry of a factor of 2. In addition, the difference in the line profile shape is significant when these new Cycle 7 data are compared to Cycle 0 data of the same SO transitions. We discuss the different physical and chemical mechanisms that might cause this asymmetry and time variability, including disk winds, disk warps, and a shock triggered by a (forming) planet. We propose that SO is enhanced in the cavity by the presence of a giant planet. The SO asymmetry complements evidence for hot circumplanetary material around giant planet HD 100546 c that is traced via CO ro-vibrational emission. This work sets the stage for further observational and modelling efforts to detect and understand the chemical imprint of a forming planet on its parent disk.
Towards a new era in giant exoplanet characterisation
Authors: Müller Simon , Helled Ravit
Published: November 2022

Determining the composition of giant exoplanets is crucial for understanding their origin and evolution. However, planetary bulk composition is not measured directly but must be deduced from a combination of mass-radius measurements, knowledge of the planetary age and evolution simulations. Accurate determinations of stellar ages, mass-radius measurements, and atmospheric compositions from upcoming missions can significantly improve the determination of the heavy-element mass in giant planets. In this paper we first demonstrate the importance of an accurate age measurement, as expected from Plato, in constraining planetary properties. Well-determined stellar ages can reduce the bulk-metallicity uncertainty by up to a factor of two. We next infer the bulk metallicity of warm giants from the Ariel mission reference sample and identify the Ariel high-priority targets for which a measured atmospheric metallicity can clearly break the degeneracy in the inferred composition. We show that knowledge of the atmospheric metallicity can broadly reduce the bulk-metallicity uncertainty by a factor of four to eight. We conclude that accurate age determinations from Plato and atmospheric measurements by Ariel and the James Webb Space Telescope will play a key role in revealing the composition of giant exoplanets.
Sub-stellar engulfment by a main-sequence star: Where is the lithium?
Authors: Cabezón R. M. , Abia C. , Domínguez I. , García-Senz D.
Published: November 2022

Context. Since the discovery of exoplanetary systems, questions have been raised as to the sub-stellar companions that can survive encounters with their host star, and how this interaction may affect the internal structure and evolution of the hosting star, and particularly its surface chemical composition.

Aims. We study whether the engulfment of a brown dwarf (BD) by a solar-like main-sequence (MS) star can significantly alter the structure of the star and the Li content on its surface.

Methods. We performed 3D smoothed particle hydrodynamics simulations of the engulfment of a BD with masses 0.01 and 0.019 M⊙, on an MS star of 1 M⊙ and solar composition, in three different scenarios: a head-on collision, a grazing collision with an impact parameter η = 0.5 R⊙, and a merger. We studied the dynamics of the interaction in detail, and the relevance of the type of interaction and the mass of the BD on the final fate of the sub-stellar object and the host star in terms of mass loss of the system, angular momentum transfer, and changes in the Li abundance on the surface of the host star.

Results. In all the studied scenarios, most of the BD mass is diluted in the denser region of the MS star. Only in the merger scenario a significant fraction (∼40%) of the BD material would remain in the outer layers. We find a clear increase in the surface rotational velocity of the host star after the interaction, ranging between 25 km s−1 (grazing collision) to 50 km s−1 (merger). We also find a significant mass loss from the system (in the range 10−4 − 10−3 M⊙) due to the engulfment, which in the case of the merger may form a circumstellar disk-like structure. Assuming that neither the depth of the convective envelope of the host star nor its mass content are modified during the interaction, a small change in the surface Li abundance in the head-on and grazing collisions is found. However, in the merger we find large Li enhancements, by factors of 20 − 30, depending on the BD mass. Some of these features could be detected observationally in the host star, provided they remained for a long enough time.

Conclusions. In our 3D simulations, a sizable fraction of the BD survives long enough to be mixed with the inner core of the MS star. This is at odds with previous suggestions based on 1D simulations. In some cases the final surface rotational velocity is very high, coupled with enough mass loss that may form a circumstellar disk. Merger scenarios tend to dilute considerably more BD material on the surface of the MS star, which could be detected as a Li-enhancement. The dynamic of the simulated scenarios suggests the development of asymmetries in the structure of the host star that can only be tackled with 3D codes, including the long-term evolution of the system.
ISPY: NACO Imaging Survey for Planets around Young stars
Authors: Cugno G. , Pearce T. D. , Launhardt R. , Bonse M. J. , Ma J. , Henning T. , Quirrenbach A. , Ségransan D. , Matthews E. C. , Quanz S. P. , Kennedy G. M. , Müller A. , Reffert S. , Rickman E. L.
Published: November 2022

Context. Planet formation is a frequent process, but little observational constraints exist about the mechanisms involved, especially for giant planets at large separation. The NaCo-ISPY large program is a 120 night L′-band direct imaging survey aimed at investigating the giant planet population on wide orbits (a > 10 au) around stars hosting disks.

Aims. Here we present the statistical analysis of a subsample of 45 young stars surrounded by protoplanetary disks (PPDs). This is the largest imaging survey uniquely focused on PPDs to date. Our goal is to search for young forming companions embedded in the disk material and to constrain their occurrence rate in relation to the formation mechanism.

Methods. We used principal component analysis based point spread function subtraction techniques to reveal young companions forming in the disks. We calculated detection limits for our datasets and adopted a black-body model to derive temperature upper limits of potential forming planets. We then used Monte Carlo simulations to constrain the population of forming gas giant companions and compare our results to different types of formation scenarios.

Results. Our data revealed a new binary system (HD 38120) and a recently identified triple system with a brown dwarf companion orbiting a binary system (HD 101412), in addition to 12 known companions. Furthermore, we detected signals from 17 disks, two of which (HD 72106 and T CrA) were imaged for the first time. We reached median detection limits of L′ = 15.4 mag at 2″.0, which were used to investigate the temperature of potentially embedded forming companions. We can constrain the occurrence of forming planets with semi-major axis a in [20–500] au and Teff in [600–3000] K to be 21.2-13.6+24.3%, 14.8-9.6+17.5%, and 10.8-7.0+12.6% for Rp = 2, 3, 5 RJ, which is in line with the statistical results obtained for more evolved systems from other direct imaging surveys. These values are obtained under the assumption that extinction from circumstellar and circumplanetary material does not affect the companion signal, but we show the potential impact these factors might have on the detectability of forming objects.

Conclusions. The NaCo-ISPY data confirm that massive bright planets accreting at high rates are rare. More powerful instruments with better sensitivity in the near- to mid-infrared are likely required to unveil the wealth of forming planets sculpting the observed disk substructures.
Multi-objective optimization model for blood supply chain network design considering cost of shortage and substitution in disaster
Authors: Hosseini Seyed Mohammad Hassan , Behroozi Forough , Sana Shib Sankar
Published: November 2022

The problem of network design of blood supply chains is traditionally studied considering a maximum of three objective functions. In the real world, however, there are always many conflicting objectives for different stakeholders. This paper addresses a blood supply chain (BSC) network design problem to optimize the costs of blood shortage and substitution in addition to other common objective functions. To this end, four important objectives that decision makers are always faced with in disaster are considered: (1) minimizing the total cost, (2) minimizing transportation time, (3) minimizing total unsatisfied demand, and (4) maximizing the total reliability. A mixed-integer linear programming (MIP) model is proposed to formulate the problem at hand. Since this problem is known to be strongly NP-hard, the intelligent NSGA-II algorithm is applied to solve it in a reasonable time. Data from a real case study is used to evaluate the performance of the proposed solution method. The comparison of the results of the proposed algorithm with the mathematical model confirms the accuracy of the proposed method. Furthermore, the analysis of the results indicates the superiority of the proposed model over previous studies. Moreover, the proposed algorithm provides a wide range of suitable solutions. Therefore, different alternatives are presented to the decision makers to make a trade-off according to their preferences.
Chemoenzymatic Enantioselective Synthesis of the Hancock Alkaloids (S)- and (R)-Galipeine, (S)-Cuspareine, (S)-Galipinine, and (S)-Angustureine
Authors: Diaz-Muñoz Gaspar , da Cruz Nilton Gonçalves , de Miranda Amanda Silva , Vieira Henriete da Silva , Kohlhoff Markus , Mendonça João Guilherme Pereira , Diaz Marisa Alves Nogueira
Published: November 2022

The enantioselective synthesis of the Hancock 1,2,3,4-tetrahydroquinoline alkaloids (S)-galipeine, (S)-cuspareine, (S)-galipinine, and (S)-angustureine and the nonnatural enantiomer (R)-galipeine is described herein. The target compounds were obtained in five steps from a racemic quinaldinic acid derived α-amino ester in overall yields of 21.2% to 37.5%. The synthetic route comprised two key steps: an enzymatic kinetic resolution to control the C-2 stereocenter, affording (R)- and (S)-α-amino esters as key chiral intermediates with 94% and 72% ee, respectively, and Wittig olefination of (R)- and (S)-α-amino aldehyde synthons with the corresponding phosphonium salts using a phase-transfer system (t-BuOH/CH2Cl2), thereby allowing the introduction of alkyl substituents at C-2. Finally, the enantioselective synthesis was concluded with the catalytic hydrogenation of olefinic bonds on the Wittig adducts to furnish the target Hancock alkaloids, including (R)-galipeine, whose synthesis is described here for the first time.
Challenging Cases in Neurology: Neurologic Complications of COVID-19
Authors: Horta Lucas , Bakhtyari Ava , Greige Tatiana , Anand Pria
Published: November 2022

Since the first reported cases of pneumonia in December 2019, coronavirus disease 2019 (COVID-19) has rapidly become recognized as a multisystem illness, with known effects on virtually every organ system. In particular, neurologic complications of COVID-19 have been reported since the beginning of the pandemic in both ambulatory patients with mild disease and critically ill patients. Although it remains unclear whether severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has the potential to directly invade the central nervous system, strokes and other neurovascular complications, sequelae of critical illness and metabolic derangements, parainfectious inflammatory disorders, and a poorly understood post-COVID syndrome have all been reported in patients with COVID-19. Here, we describe cases representing a diverse range of neurologic complications in patients infected with COVID-19.
Increased Number of Functional Tics Seen in Danish Adolescents during the COVID-19 Pandemic
Authors: Okkels Kirstine Birkebæk , Skov Liselotte , Klansø Susanne , Aaslet Lone , Grejsen Judy , Reenberg Annika , Sørensen Camilla Birgitte , Debes Nanette Marinette Monique Mol
Published: November 2022

Background Global increase in functional tics in adolescents has been observed. Differentiating functional from classic tics is important since pathophysiology and treatment differ. We investigated possible triggers for development of functional tics and discuss the possible role of the coronavirus disease 2019 (COVID-19) pandemic and social media exposure in cases of functional tics seen during this period. Moreover, the treatment, and its efficacy is discussed.

Methods Medical records of 28 Danish adolescents diagnosed with functional tics at the National Tourette Clinic, Department of Pediatrics, Herlev University Hospital, Denmark, from May 2020 to June 2021 have been retrospectively reviewed. Descriptive statistical analyses were used to analyze the data.

Main Findings A total of 28 patients diagnosed with functional tics were included, 96.4% girls and 3.6% boys, mean age 14.4 years. Tic phenomenology differed from classic tics with more complex tics and no rostrocaudal progression. Note that 69.2% reported harmful tics. Also, 78.6% had trauma/precipitating event and 40% denounced lockdown related to the COVID-19 pandemic as trigger, both prior to onset of functional tics. Note that 60.7% reported psychiatric symptoms/diagnoses, 42.9% had a first-degree family member with psychiatric symptoms/diagnoses, and 96.4% were exposed to tics on social media prior to onset. Treatment consisted of psychoeducation, elements from cognitive behavioral therapy, and focus on psychiatric symptoms. All patients responded to the treatment.

Conclusion The vulnerability of the adolescents is characteristic. Treatment strategy has shown immediate positive effect. Consequences of the COVID-19 pandemic in combination with exposure to tics on social media could be part of the cause for the increase in number of functional tics.
Exposure and Response Prevention for Children and Adolescents with Tourette Syndrome Delivered via Web-Based Videoconference versus Face-to-Face Method
Authors: Soerensen Camilla Birgitte , Lange Theis , Jensen Sidsel Normann , Grejsen Judy , Aaslet Lone , Skov Liselotte , Debes Nanette Mol
Published: November 2022

Chronic tic disorders, such as Tourette syndrome, are characterized by motor and vocal tics. Tics present a considerable burden for some patients, and therefore, effective treatment is important. One evidence-based treatment option is a behavioral therapy called exposure and response prevention (ERP). Despite its effectiveness, access to ERP remains limited due to a lack of treatment sites. Web-based videoconferences can connect patients at home with a therapist located in the hospital, allowing for treatment delivery over a wide geographic area. The primary aim of this study was to compare the development of tics during and 1 year after ERP delivery, respectively, via web-based videoconferences and traditional face-to-face methods in a naturalistic setting. In total, 116 patients treated using either the face-to-face method (n = 72) or web-based videoconferences (n = 44) were included. The primary outcome measure was tic severity. In both training modalities, tic severity decreased during ERP and the effect lasted in the follow-up period. No statistically significant differences in tic severity between the training modalities were found at baseline, last training session, or at follow-up. Our results suggest that ERP delivered via web-based videoconferences is a good alternative to the traditional face-to-face method.
All-Arthroscopic Triangular Fibrocartilage Complex Ligamentoplasty: Technique and Results
Authors: Carratalá Vicente , Lucas Francisco Javier , Miranda Ignacio , Martínez Cristóbal , Guisasola Eva
Published: November 2022

Objective The aim of the study is to describe the modified all-arthroscopic technique for triangular fibrocartilage complex (TFCC) ligamentoplasty in chronic injuries of the TFCC with distal radioulnar joint (DRUJ) instability, and to present the results obtained.

Methods A prospective study was conducted including 11 consecutive patients with chronic TFCC injury with DRUJ instability who underwent an all-arthroscopic TFCC ligamentoplasty. During follow-up, the range of joint motion, grip strength, pain according to the visual analog scale (VAS), functional outcomes according to the Mayo Wrist Score (MWS), and the QuickDASH Score were measured, and any complications and necessary reinterventions were recorded

Results We analyzed 11 patients with distal radioulnar ligament injury treated using the all-arthroscopic ligamentoplasty technique. Mean follow-up was 31.5 ± 4.4 (range 12–58) months. The technique presented achieved DRUJ stability in 100% of cases at 12 months. Grip strength and pain, showed a statistically significant improvement between the preoperative score and the two postoperative assessments. Functional assessment using the QuickDASH score and the MWS also improved significantly.

Conclusion The all-arthroscopic technique for the reconstruction of irreparable peripheral TFCC tears is a reliable technique, intended not only to minimize the surgical trauma to reduce postoperative pain and to facilitate rehabilitation, but also to improve both the quality of the reconstruction and the functional outcome.
Association between the Distribution of Adipose Tissue and Outcomes in Acute Pancreatitis: A Comparison of Methods of Fat Estimation
Authors: Dawra Saurabh , Gupta Pankaj , Yadav Neha , Singh Anupam K , Samanta Jayanta , Sinha Saroj K , Sandhu Manavjit Singh , Kochhar Rakesh
Published: November 2022

Purpose To assess the correlation between abdominal fat measured at computed tomography (CT) and dual-energy X-ray absorptiometry (DXA) and association with clinical outcomes in patients with acute pancreatitis (AP).

Methods This prospective study comprised consecutive patients with AP who underwent abdominal CT and DXA. Fat estimation was done on whole-body DXA and abdominal CT. Correlations among body mass index (BMI), waist circumference (WC), DXA, and CT fat measurements were determined. The association between fat measurements and clinical outcomes was assessed.

Results Fifty-nine patients (mean age 38.2 years, 48 males) were included. There was a strong correlation (r = 0.691–0.799) between DXA and CT fat estimation. In addition, there was a significant association of the visceral adipose tissue (VAT) on DXA and CT with the severity of AP (p = 0.039 and 0.021, respectively) and the need for drainage of collections (p = 0.026 and 0.008, respectively). There was a weak correlation of the BMI and WC with the length of hospitalization (LOH) (r = 0.121, 0.190, respectively) and length of intensive care unit stay (LOICU) (r = 0.211, 0.197), while there was a moderate to strong correlation of the truncal fat and visceral fat on DXA and total adipose tissue and VAT on CT with LOH (r = 0.562, 0.532, 0.602 and 0.614, respectively) and LOICU (r = 0.591, 0.577, 0.636, and 0.676, respectively).

Conclusion In conclusion, fat indices measured on DXA and CT are associated with the severity of AP. In addition, the fat measurements at DXA are strongly correlated with those obtained at CT.
Direct numerical simulation of compressible turbulence accelerated by graphics processing unit: An open-source high accuracy accelerated computational fluid dynamic software
Authors: Dang Guanlin , Liu Shiwei , Guo Tongbiao , Duan Junyi , Li Xinliang
Published: November 2022

This paper introduces open-source computational fluid dynamics software named open computational fluid dynamic code for scientific computation with graphics processing unit (GPU) system (OpenCFD-SCU), developed by the authors for direct numerical simulation of compressible wall-bounded turbulence. This software is based on the finite difference method and is accelerated by the use of a GPU, which provides an acceleration by a factor of more than 200 compared with central processing unit (CPU) software based on the same algorithm and a number of Message Passing Interface processes, and the running speed of OpenCFD-SCU with just 512 GPUs exceeds that of CPU software with 130 000 CPUs. GPU-Stream technology is used to implement overlap of computing and communication, achieving 98.7% parallel weak scalability with 24 576 GPUs. The software includes a variety of high-precision finite difference schemes and supports a hybrid finite difference scheme, enabling it to provide both robustness and high precision when simulating complex supersonic and hypersonic flows. When used with the wide range of supercomputers currently available, the software should be able to improve the performance of large-scale simulations by up to two orders on the computational scale. Then, OpenCFD-SCU is applied to a validation and verification case of a Mach 2.9 compression ramp with mesh numbers up to 31.2 × 109.
Numerical simulation of thermochemical non-equilibrium flow-field characteristics around a hypersonic atmospheric reentry vehicle
Authors: Yu Minghao , Qiu Zeyang , Zhong Bowen , Takahashi Yusuke
Published: November 2022

A multi-physics thermochemical non-equilibrium model is established to study the flow characteristics of the plasma sheath around an atmospheric reentry demonstrator. This model includes the tight coupling of Navier–Stokes equations, 54 chemical reactions of air, and a four-temperature model. The processes of dissociation, ionization, and the internal energy exchanges of air components were successfully simulated during aerodynamic heating of the reentry vehicle. The distributions of plasma sheath temperature, the molar fraction of air species, stagnation pressure, surface pressure, and electron number density around the reentry vehicle were obtained at different flight altitudes. Additionally, to validate the numerical model developed in this study, the flow characteristics of the Radio Attenuation Measurement-C-II (RAM-C-II) vehicle are also simulated and then compared with corresponding experimental data. They show good consistency in general. It is found that when the vehicle is at a high flight altitude, there is a strong thermochemical non-equilibrium phenomenon around the vehicle. However, the plasma sheath tends to be in local thermal equilibrium at a low flight altitude. The distance from the shock layer to the stagnation point decreases with a decrease in reentry altitude from 90 to 65 km but increases with a decrease from 65 to 40 km. The electron number density in the shock layer is maximum. The distribution of the electron number density in the wake region differs significantly at different flight altitudes.
The relationship between milk oestradiol concentrations and oestrus activity in lactating Holstein–Friesian cows
Authors: Zebari Hawar M. , Rutter S. Mark , Bleach Emma C. L.
Published: November 2022

Context Detecting oestrus to facilitate the optimal timing of artificial insemination is key to optimal reproductive performance in dairy cows. Aims The aims of the present study were to investigate the relationship between activity and milk oestradiol concentrations during oestrus. Methods Accelerometers (IceQubes, IceRobotics Ltd, UK) were used to monitor the activity (the number of steps per day) of 37 lactating Holstein–Friesian cows during the peri-oestrus period. Daily milk samples were analysed for oestradiol and progesterone concentrations. Key results An increase in activity sufficient to generate an oestrus alert (behavioural oestrus) from an activity sensor (GEA Rescounter II) was detected in 29 of 37 (78%) cows. Milk oestradiol increased from 2.0 ± 0.5 pg/mL 4 days before oestrus to 8.3 ± 1.1 pg/mL on the day of behavioural oestrus, then fell to 2.6 ± 0.6 pg/mL by 3 days afterwards. Similarly, activity also increased and peaked on the day of oestrus. However, in 8 of 37 (22%) cows, although milk oestradiol concentrations increased following the fall in progesterone, there was no significant increase in activity (silent oestrus). Milk oestradiol concentrations were positively correlated (r = 0.37; P = 0.03) with activity on the day of oestrus. Cows that subsequently became pregnant took a similar number of steps (2806 ± 282.3 vs 2850 ± 372.5 steps for PD+ vs PD− cows respectively) but had higher oestradiol concentrations (11.2 ± 2.06 vs 5.1 ± 0.51 pg/mL for PD+ vs PD− cows respectively) on the day of oestrus than did cows that did not become pregnant. Conclusions Increases in oestradiol concentrations above a threshold of approximately 10 pg/mL are associated with an increased activity, and higher oestral oestradiol concentrations are associated with a higher rate of pregnancy following insemination. Implications This study has demonstrated the significance of oestradiol concentration to the fertility of dairy cows. Thus, strategies to enhance oestradiol secretion may enhance fertility. Further, milk oestradiol measures may be developed as an aid to oestrus detection in lactating dairy cows, although further studies are required to determine whether on-farm assessment of milk oestradiol concentration can be developed to add to the repertoire of biomarkers of oestrus in lactating cattle.
Overcoming the social stigma of losing a pet: Considerations for counseling professionals
Authors: Crossley Michelle Kay , Rolland Colleen
Published: November 2022

During the COVID-19 pandemic, individuals found themselves spending more time with their pets and relied on them to maintain normalcy and provide security during isolation. Pets play a significant role in the lives of their caregivers, taking on different attachment roles depending on the needs of the individual. Grieving the death of a pet continues to be disenfranchised in society. Perceptions of judgment can lead individuals to grieve the loss without social support. The present review builds on research in the field of pet loss and human bereavement and factors in the impact of the COVID-19 pandemic on human-animal attachment A goal of the present review is to provide counselors with perspectives to consider in their practice when working with clients who have attachments to their companion animals and to acknowledge the therapeutic benefits of working through the grief process to resolution as a way to continue the bond with a deceased pet.
Natural aging of heterogeneous arc-welded AA6061-AA7075 joints with nanocomposite filler
Authors: Murali Narayanan , Zheng Shiqi , Chi Yitian , Li Xiaochun
Published: November 2022

We report the dissimilar joining of aluminium alloys 6061 and 7075 using filler rods nano-treated with TiC nanoparticles. TiC enables the formation of a fine and equiaxial weld metal microstructure while preventing the formation of hot cracks. Dissimilar joints were also naturally aged, and their strength evolutions were tracked over 8 weeks and compared to a nano-treated, homogeneous AA7075 joint. Heterogeneous weld metals regained over 30 HV with a mix of MgZn2 and Mg2Si strengthening phases. Nano-treatment thus shows great promise, being able to facilitate the fusion welding of a traditionally difficult-to-weld system and enable a natural aging response between two artificially aged alloys.
Cosmological particle creation in Weyl geometry
Authors: Berezin V A , Dokuchaev V I
Published: November 2022

We investigated the possibility of the homogeneous and isotropic cosmological solution in Weyl geometry, which differs from the Riemannian geometry by adding the so called Weyl vector. The Weyl gravity is obtained by constructing the gravitational Lagrangian both to be quadratic in curvatures and conformal invariant. It is found that such solution may exist provided there exists the direct interaction between the Weyl vector and the matter fields. Assuming the matter Lagrangian is that of the perfect fluid, we found how such an interaction can be implemented. Due to the existence of quadratic curvature terms and the direct interaction the perfect fluid particles may be created straight from the vacuum, and we found the expression for the rate of their production which appeared to be conformal invariant. In the case of creating the Universe ‘from nothing’ in the vacuum state, we investigated the problem, whether this vacuum may persist or not. It is shown that the vacuum may persist with respect to producing the non-dust matter (with positive pressure), but cannot resist to producing the dust particles. These particles, being non-interactive, may be considered as the candidates for dark matter.
Shadow of Kottler black hole in the presence of plasma for a co-moving observer
Authors: Das Anish , Saha Ashis , Gangopadhyay Sunandan
Published: November 2022

In this paper, we discussed the shadow of a static, spherically symmetric black hole geometry in presence of a positive cosmological constant

Λ
>
0

. We analysed the black hole shadow both in absence and presence of plasma. Then we study the black hole shadow from the point of view of a comoving observer. We display the plots for the angular shadow size as measured by a comoving observer. The effects of the cosmological constant Λ and plasma parameter k on the angular size of the black hole shadow have been investigated in detail. Finally, by using the observed angular size of M87

∗

and Sgr A

∗

black hole, we constrain the value of the plasma parameter k with a specific observational value of the cosmological constant Λ (or the Hubble constant H
0).
When artificial parameter evolution gets real: particle filtering for time-varying parameter estimation in deterministic dynamical systems
Authors: Arnold Andrea
Published: November 2022

Estimating and quantifying uncertainty in unknown system parameters from limited data remains a challenging inverse problem in a variety of real-world applications. While many approaches focus on estimating constant parameters, a subset of these problems includes time-varying parameters with unknown evolution models that often cannot be directly observed. This work develops a systematic particle filtering approach that reframes the idea behind artificial parameter evolution to estimate time-varying parameters in nonstationary inverse problems arising from deterministic dynamical systems. Focusing on systems modeled by ordinary differential equations, we present two particle filter algorithms for time-varying parameter estimation: one that relies on a fixed value for the noise variance of a parameter random walk; another that employs online estimation of the parameter evolution noise variance along with the time-varying parameter of interest. Several computed examples demonstrate the capability of the proposed algorithms in estimating time-varying parameters with different underlying functional forms and different relationships with the system states (i.e. additive vs. multiplicative).