bluuebunny/crossref_metadata_2025 huggingface dataset:
Synergistic effect of cold atmospheric pressure plasma and free or liposomal doxorubicin on melanoma cells
Authors: Pefani-Antimisiari Konstantina , Athanasopoulos Dimitrios K. , Marazioti Antonia , Sklias Kyriakos , Rodi Maria , de Lastic Anne-Lise , Mouzaki Athanasia , Svarnas Panagiotis , Antimisiaris Sophia G.
Published: July 2021

The aim of the present study was to investigate combined effects of cold atmospheric plasma (CAP) and the chemotherapeutic drug doxorubicin (DOX) on murine and human melanoma cells, and normal cells. In addition to free drug, the combination of CAP with a liposomal drug (DOX-LIP) was also studied for the first time. Thiazolyl blue tetrazolium bromide (MTT) and Trypan Blue exclusion assays were used to evaluate cell viability; the mechanism of cell death was evaluated by flow cytometry. Combined treatment effects on the clonogenic capability of melanoma cells, was also tested with soft agar colony formation assay. Furthermore the effect of CAP on the cellular uptake of DOX or DOX-LIP was examined. Results showed a strong synergistic effect of CAP and DOX or DOX-LIP on selectively decreasing cell viability of melanoma cells. CAP accelerated the apoptotic effect of DOX (or DOX-LIP) and dramatically reduced the aggressiveness of melanoma cells, as the combination treatment significantly decreased their anchorage independent growth. Moreover, CAP did not result in increased cellular uptake of DOX under the present experimental conditions. In conclusion, CAP facilitates DOX cytotoxic effects on melanoma cells, and affects their metastatic potential by reducing their clonogenicity, as shown for the first time.
A comparative study of mesenchymal stem cell transplantation and NTG-101 molecular therapy to treat degenerative disc disease
Authors: Matta Ajay , Karim Muhammad Zia , Gerami Hoda , Benigno Bettina , Erwin W. Mark
Published: July 2021

Cellular replacement therapy using mesenchymal stem cells (MSCs) and/or the delivery of growth factors are at the forefront of minimally invasive biological treatment options for Degenerative Disc Disease (DDD). In this study, we compared the therapeutic potential of a novel drug candidate, NTG-101 to MSCs, including rat cartilage derived stem cells (rCDSCs), bone marrow stem cells (rBMSCs) and human Umbilical Cord Derived Mesenchymal Stem Cells (hUCMSCs) for the treatment of DDD. We induced DDD using a validated image-guided needle puncture injury in rat-tail IVDs. Ten weeks post-injury, animals were randomized and injected with MSCs, NTG-101 or vehicle. At the end of the study, histological analysis of the IVD-Nucleus Pulposus (NPs) injected with NTG-101 or rCDSCs showed a healthy or mild degenerative phenotype in comparison to vehicle controls. Immunohistochemical analysis revealed strong expression of aggrecan, collagen 2, brachyury and Oct4 in IVD-NPs injected with NTG-101. Our results also demonstrated suppression of inflammation induced p38 and NFκB resulting in inhibition of catabolic genes, but activation of Smad-2/3, Erk-1/2 and Akt-dependent signaling inducing anabolic genes in IVD-NP on treatment with NTG-101. In conclusion, a single injection of NTG-101 into the degenerative disc demonstrated superior benefits compared to stem cell transplantation.
Preoperative diagnosis of BRCA1/2 mutation impacts decision-making for risk-reducing mastectomy in breast cancer patients
Authors: Woo Jinsun , Gwak Geumhee , Park Inseok , Bae Byung Noe , Lee Se Kyung , Chae Byung Joo , Yu Jonghan , Lee Jeong Eon , Kim Seok Won , Nam Seok Jin , Ryu Jai Min
Published: July 2021

Decision to undergo risk-reducing mastectomy (RRM) needs to consider several factors, including patient’s preference, surgeon’s preference, family history, and genetic predisposition. The aim of this study was to examine whether preoperative diagnosis ofBRCA1/2mutation status could influence surgical decision-making in newly diagnosed breast cancer patients. We retrospectively reviewed ipsilateral breast cancer patients withBRCA1/2mutation who underwent primary surgery between January 2008 and November 2019 at a single institution in Korea. Of 344 eligible patients, 140 (40.7%) patients were aware of their mutation status ‘prior to surgery’, while 204 (59.3%) did not. Contralateral RRM rate was significantly higher in the group withBRCA1/2mutation status identified ‘prior to surgery’ compared to the group with mutation status identified ‘after surgery’ [45.0% (63/140) vs. 2.0% (4/204)] (p < 0.001). Reduced turnaround time ofBRCA1/2testing (p < 0.001) and the use of neoadjuvant chemotherapy (p < 0.001) were associated withBRCA1/2mutation status identified prior to surgery. Although not statistically significant, higher incidence of developing contralateral breast cancer forBRCA1/2mutation carriers who underwent ipsilateral surgery-only compared to those who underwent contralateral RRM was observed [12.1% (95% CI: 7.7–17.7%)] (p = 0.1618). Preoperative diagnosis ofBRCA1/2mutation could impact surgical decision-making for breast cancer patients to undergo risk-reducing surgery at the time of initial surgery.
Biaxial 360-degree scanning LIDAR using a liquid crystal control
Authors: Nishiwaki Seiji
Published: July 2021

Sophisticated non-mechanical technology for LIDARs is needed to realize safe autonomous cars. We have confirmed the operating principle of a non-mechanical LIDAR by combining concentric circular-grating couplers (CGCs) with a coaxially aligned rod lens. Laser light incident vertically on the center of the inner CGC along the center axis of the lens is radiated from the outer CGC and passes through the side surface of the lens. It is converted to a parallel beam that scans in two axes by applying voltages to two area-segmented electrode layers sandwiching the CGCs and a liquid crystal layer formed on the CGCs. We have demonstrated scanning whose motion ranges were 360 degrees horizontally and 10° vertically. A beam with a spread angle of 0.3° × 0.8° at a minimum swept vertically up to a frequency of 100 Hz and ten equally spaced beams scanned rotationally with a 6-degree cycle variation of spread of between 0.8° and 3.5°.
Structural basis for the structural dynamics of human mitochondrial chaperonin mHsp60
Authors: Wang Joseph Che-Yen , Chen Lingling
Published: July 2021

Human mitochondrial chaperonin mHsp60 is essential for mitochondrial function by assisting folding of mitochondrial proteins. Unlike the double-ring bacterial GroEL, mHsp60 exists as a heptameric ring that is unstable and dissociates to subunits. The structural dynamics has been implicated for a unique mechanism of mHsp60. We purified active heptameric mHsp60, and determined a cryo-EM structure of mHsp60 heptamer at 3.4 Å. Of the three domains, the equatorial domains contribute most to the inter-subunit interactions, which include a four-stranded β sheet. Our structural comparison with GroEL shows that mHsp60 contains several unique sequences that directly decrease the sidechain interactions around the β sheet and indirectly shorten β strands by disengaging the backbones of the flanking residues from hydrogen bonding in the β strand conformation. The decreased inter-subunit interactions result in a small inter-subunit interface in mHsp60 compared to GroEL, providing a structural basis for the dynamics of mHsp60 subunit association. Importantly, the unique sequences are conserved among higher eukaryotic mitochondrial chaperonins, suggesting the importance of structural dynamics for eukaryotic chaperonins. Our structural comparison with the single-ring mHsp60-mHsp10 shows that upon mHsp10 binding the shortened inter-subunit β sheet is restored and the overall inter-subunit interface of mHsp60 increases drastically. Our structural basis for the mHsp10 induced stabilization of mHsp60 subunit interaction is consistent with the literature that mHsp10 stabilizes mHsp60 quaternary structure. Together, our studies provide structural bases for structural dynamics of the mHsp60 heptamer and for the stabilizing effect of mHsp10 on mHsp60 subunit association.
The impact of different thresholds on optical coherence tomography angiography images binarization and quantitative metrics
Authors: Arrigo Alessandro , Aragona Emanuela , Saladino Andrea , Amato Alessia , Bandello Francesco , Battaglia Parodi Maurizio
Published: July 2021

Optical coherence tomography angiography (OCTA) provides several data regarding the status of retinal capillaries. This information can be further enlarged by employing quantitative metrics, such as vessel density (VD). A mandatory preliminary step of OCTA quantification is image binarization, a procedure used to highlight retinal capillaries on empty background. Although several binarization thresholds exist, no consensus is reached about the thresholding technique to be used. In this study, we tested thirteen binarization thresholds on a dataset made by thirty volunteers. The aim was to assess the impact of binarization techniques on: (I) detection of retinal capillaries, assessed by the calculation of overlapping percentages between binarized and original images; (II) quantitative OCTA metrics, including VD, vessel tortuosity (VT) and vessel dispersion (Vdisp); (III) foveal avascular zone (FAZ) detection. Our findings showed Huang, Li, Mean and Percentile as highly reliable binarization thresholds (p < 0.05), whereas the worst binarization thresholds were Intermodes, MaxEntropy, RenylEntropy and Yen (p < 0.05). All the thresholds variably underestimated VD metric and FAZ detection, with respect to the original OCTA images, whereas VT and Vdisp turned out to be more stable. The usage of a Fixed threshold resulted extremely useful to reduce VD and FAZ underestimations, although bound to operators’ experience.
Indexing cerebrovascular health using near-infrared spectroscopy
Authors: Afkhami Rashid , Walker Frederick R. , Ramadan Saadallah , Wong Rachel , Johnson Sarah J.
Published: July 2021

Near-infrared spectroscopy (NiRS) is a relatively new technology of brain imaging with its potential in the assessment of cerebrovascular health only recently discovered. Encouraging early results suggest that NiRS can be used as an inexpensive and portable cerebrovascular health tracking device using a recently proposed pulse relaxation function (PReFx). In this paper, we propose a new NiRS timing index, $$\text {TI}_{\rm NiRS}$$

TI
NiRS

, of cerebrovascular health. $$\text {TI}_{\rm NiRS}$$

TI
NiRS

is a novel use of the NiRS technology. $$\text {TI}_{\rm NiRS}$$

TI
NiRS

is motivated by the previously proved relationship of the timing of the reflected wave with vascular resistance and compliance in the context of pressure waveforms. We correlated both $$\text {TI}_{\rm NiRS}$$

TI
NiRS

and PReFx against age, a non-exercise cardiorespiratory fitness (CRF) index, and two existing indices of cerebrovascular health, namely transcranial Doppler (TCD) augmentation index, $$\text {AI}_{\rm TCD}$$

AI
TCD

, and magnetic resonance imaging (MRI) blood flow pulsatility index, $$\text {PI}_{\rm MRI}$$

PI
MRI

. The $$\text {TI}_{\rm NiRS}$$

TI
NiRS

correlations with Age, CRF, $$\text {PI}_{\rm MRI}$$

PI
MRI

and $$\text {AI}_{\rm TCD}$$

AI
TCD

all are significant, i.e., $$r=0.53$$

r
=
0.53

($$p=0.002$$

p
=
0.002

), $$r=-0.44$$

r
=
-
0.44

($$p=0.011$$

p
=
0.011

), $$r=0.45$$

r
=
0.45

($$p=0.012$$

p
=
0.012

) and $$r=0.46$$

r
=
0.46

($$p=0.010$$

p
=
0.010

), respectively. PReFx, however, did not have significant correlations with any of the vascular health factors. The proposed timing index is a reliable indicator of cerebrovascular aging factors in the NiRS waveform.
APOE E4 is associated with hyperlipidemia and obesity in elderly schizophrenic patients
Authors: Li Wei , Liu Fengju , Liu Rui , Zhou Xinmei , Li Guanjun , Xiao Shifu
Published: July 2021

Obesity is a critical issue in patients with schizophrenia, which is considered to be brought about by both environmental and genetic factors. Apolipoprotein E (APOE) gene polymorphisms might be involved in the pathogenesis of schizophrenia, however, the effect of APOE gene polymorphism on obesity has never been investigated in Chinese aging with schizophrenia. This cross-sectional study was to investigate the effect of obesity on cognitive and psychiatric symptoms in elderly participants with schizophrenia. At the same time, we also discussed the inner link between APOE E4 and obesity. 301 elderly participants with schizophrenia and 156 normal controls were included in the study. Their cognitive function was assessed using the Montreal Cognitive Assessment (MoCA), psychiatric symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS), and APOE gene polymorphism was determined by polymerase chain reaction (PCR). The prevalence of obesity in elderly schizophrenic patients and healthy controls accounted for 15.9% (48/301) and 10.3% (16/156), respectively, with no statistically significant difference. By using stepwise linear regression analysis, we found that elevated fasting blood glucose, hypertension, and hyperlipidemia were risk factors for obesity in elderly schizophrenic patients. Although there was no direct correlation between APOE E4 and obesity in patients with schizophrenia, it was significantly correlated with hyperlipemia(r = − 0.154, p = 0.008), suggesting that APOE E4 may induce obesity in elderly patients with schizophrenia through hyperlipemia, However, the above conclusions do not apply to the normal elderly. What’s more, we did not find a link between obesity and cognitive function or mental symptoms for both patients with schizophrenia and normal controls. APOE E4 is associated with hyperlipidemia in elderly schizophrenic patients, which may be a risk factor for obesity, however, the above conclusion does not apply to the normal elderly.
Nomogram and a predictive model for postoperative hemorrhage in preoperative patients of laparoscopic pancreaticoduodectomy
Authors: Li Dongrui , Du Chengxu , Zhang Jiansheng , Xing Zhongqiang , Liu Jianhua
Published: July 2021

To develop a predictive model and a nomogram for predicting postoperative hemorrhage in preoperative patients undergoing laparoscopic pancreaticoduodenectomy (LPD). A total of 409 LPD patients that underwent LPD by the same surgical team between January 2014 and December 2020 were included as the training cohort. The preoperative data of patients were statistically compared and analyzed for exploring factors correlated with postoperative hemorrhage. The predictive model was developed by multivariate logistic regression and stepwise (stepAIC) selection. A nomogram based on the predictive model was developed. The discriminatory ability of the predictive model was validated using the receiver operating characteristic (ROC) curve and leave-one-out method. The statistical analysis was performed using R 3.5.1 (www.r-project.org). The predictive model including the risk-associated factors of postoperative hemorrhage was as follows: 2.695843 − 0.63056 × (Jaundice = 1) − 1.08368 × (DM = 1) − 2.10445 × (Hepatitis = 1) + 1.152354 × (Pancreatic tumor = 1) + 1.071354 × (Bile duct tumor = 1) − 0.01185 × CA125 − 0.04929 × TT − 0.08826 × APTT + 26.03383 × INR − 1.9442 × PT + 1.979563 × WBC − 2.26868 × NEU − 2.0789 × LYM − 0.02038 × CREA + 0.00459 × AST. A practical nomogram based on the model was obtained. The internal validation of ROC curve was statistically significant (AUC = 0.7758). The validation by leave-one-out method showed that the accuracy of the model and the F measure was 0.887 and 0.939, respectively. The predictive model and nomogram based on the preoperative data of patients undergoing LPD can be useful for predicting the risk degree of postoperative hemorrhage.
Combined neuromuscular electrical stimulation with motor control exercise can improve lumbar multifidus activation in individuals with recurrent low back pain
Authors: Songjaroen Sranya , Sungnak Panakorn , Piriyaprasarth Pagamas , Wang Hsing-Kuo , Laskin James J. , Wattananon Peemongkon
Published: July 2021

Motor control exercise (MCE) is commonly prescribed for patients with low back pain. Although MCE can improve clinical outcomes, lumbar multifidus muscle (LM) activation remains unchanged. Neuromuscular electrical stimulation (NMES) can be used to re-activate motor units prior to MCE which should result in increased LM activation. Therefore, this study aimed to explore the immediate effects of NMES combined with MCE on LM activation and motor performance. Twenty-five participants without low back pain (NoLBP) and 35 participants with movement control impairment (MCI) were recruited. Participants with MCI were further randomized to combined NMES with MCE (COMB) or sham-NMES with MCE (MCE) group. Ultrasound imaging was used to measure LM thickness at rest, maximum voluntary isometric contraction (MVIC), and NMES with MVIC. These data were used to calculate LM activation. Quadruped rocking backward was used to represent motor performance. LM activation and motor performance were measured at baseline and after one-session of intervention. Results showed that both COMB and MCE groups had significantly lower (P < 0.05) LM activation compared with NoLBP group at baseline. Additionally, both COMB and MCE groups demonstrated significant improvement (P < 0.05) in motor performance while COMB group demonstrated significantly greater improvement (P < 0.05) in LM activation compared with MCE group. Individuals with MCI still have persisting LM activation deficit. Our key findings suggest that combined NMES and MCE may have better ability to improve LM activation in individuals with MCI. These findings would support the utility of NMES to induce a priming effect before MCE.
Genomic context of NTRK1/2/3 fusion-positive tumours from a large real-world population
Authors: Westphalen C. B. , Krebs M. G. , Le Tourneau C. , Sokol E. S. , Maund S. L. , Wilson T. R. , Jin D. X. , Newberg J. Y. , Fabrizio D. , Veronese L. , Thomas M. , de Braud F.
Published: July 2021

Neurotrophic tropomyosin receptor kinase (NTRK) gene fusions are rare oncogenic drivers in solid tumours. This study aimed to interrogate a large real-world database of comprehensive genomic profiling data to describe the genomic landscape and prevalence of NTRK gene fusions. NTRK fusion-positive tumours were identified from the FoundationCORE® database of >295,000 cancer patients. We investigated the prevalence and concomitant genomic landscape of NTRK fusions, predicted patient ancestry and compared the FoundationCORE cohort with entrectinib clinical trial cohorts (ALKA-372-001 [EudraCT 2012-000148-88]; STARTRK-1 [NCT02097810]; STARTRK-2 [NCT02568267]). Overall NTRK fusion-positive tumour prevalence was 0.30% among 45 cancers with 88 unique fusion partner pairs, of which 66% were previously unreported. Across all cases, prevalence was 0.28% and 1.34% in patients aged ≥18 and <18 years, respectively; prevalence was highest in patients <5 years (2.28%). The highest prevalence of NTRK fusions was observed in salivary gland tumours (2.62%). Presence of NTRK gene fusions did not correlate with other clinically actionable biomarkers; there was no co-occurrence with known oncogenic drivers in breast, or colorectal cancer (CRC). However, in CRC, NTRK fusion-positivity was associated with spontaneous microsatellite instability (MSI); in this MSI CRC subset, mutual exclusivity with BRAF mutations was observed. NTRK fusion-positive tumour types had similar frequencies in FoundationCORE and entrectinib clinical trials. NTRK gene fusion prevalence varied greatly by age, cancer type and histology. Interrogating large datasets drives better understanding of the characteristics of very rare molecular subgroups of cancer and allows identification of genomic patterns and previously unreported fusion partners not evident in smaller datasets.
Travelling colourful patterns in self-organized cellulose-based liquid crystalline structures
Authors: Silva Pedro E. S. , Chagas Ricardo , Fernandes Susete N. , Pieranski Pawel , Selinger Robin L. B. , Godinho Maria Helena
Published: July 2021

Cellulose-based systems are useful for many applications. However, the issue of self-organization under non-equilibrium conditions, which is ubiquitous in living matter, has scarcely been addressed in cellulose-based materials. Here, we show that quasi-2D preparations of a lyotropic cellulose-based cholesteric mesophase display travelling colourful patterns, which are generated by a chemical reaction-diffusion mechanism being simultaneous with the evaporation of solvents at the boundaries. These patterns involve spatial and temporal variation in the amplitude and sign of the helix´s pitch. We propose a simple model, based on a reaction-diffusion mechanism, which simulates the observed spatiotemporal colour behaviour.
Phosphorylated-calix[4]arene double-deckers of single rare earth metal ions
Authors: Hosseinzadeh Marjan , Sanz Sergio , van Leusen Jan , Izarova Natalya V. , Brechin Euan K. , Dalgarno Scott J. , Kögerler Paul
Published: July 2021

Phosphorylation of calix[4]arenes imparts an increased solubility and facilitates drastically changed coordination toward lanthanide ions, resulting in mononuclear double–decker complexes.
Pd-catalyzed selective tetrafunctionalization of diiodo-o-carboranes
Authors: Ge Yixiu , Qiu Zaozao , Xie Zuowei
Published: July 2021

Highly selective Pd-catalyzed double alkenylation-iodo migration cascade reaction of diiodo-o-carboranes has been developed, leading to the one-pot tetrafunctionalization of o-carboranes with sequential activation of two cage B–I and two B–H bonds.
Bifunctional zinc and magnesium Schiff-base complexes containing quaternary ammonium side-arms for epoxide/CO2 coupling reactions
Authors: Virachotikul Arnut , Laiwattanapaisarn Nattiya , Chainok Kittipong , Phomphrai Khamphee
Published: July 2021

Bifunctional Schiff-base metal(ii) complexes having ammonium halide side-arm were developed for the epoxides/CO2 coupling reaction. High chemoselectivity for cyclic carbonates was observed and TOF was maintained even in low catalyst loading.
Deep eutectic solvent assisted zero-waste electrospinning of lignin fiber aerogels
Authors: Rong Kai , Wei Jiale , Wang Yuchen , Liu Jingwei , Qiao Zhen-An , Fang Youxing , Dong Shaojun
Published: July 2021

We developed a novel electrospinning strategy, using choline chloride–lactic acid (ChCl–LA) deep eutectic solvent (DES) as an electrospinning solvent to produce lignin fiber aerogels (LFA).
De-glycosylation and enhanced bioactivity of flavonoids from apple pomace during extraction with deep eutectic solvents
Authors: Yu Long , Bulone Vincent
Published: July 2021

Extraction and de-glycosylation of glycosylated quercetins in apple pomace was achieved using ‘green’ acidic deep eutectic solvents (DES). The antioxidant activity of the DES extracts was enhanced compared to the use of conventional organic solvents.
Recent advances in graphene quantum dot-based optical and electrochemical (bio)analytical sensors
Authors: Kalkal Ashish , Kadian Sachin , Pradhan Rangadhar , Manik Gaurav , Packirisamy Gopinath
Published: July 2021

Pictorial representation of various topics discussed in the review: GQDs synthesis strategies, properties, their regulation through heteroatom doping/surface functionalization, and (bio)analytical sensors (optical, ECL, electrochemical).
The effect of THF and the chelating modifier DTHFP on the copolymerisation of β-myrcene and styrene: kinetics, microstructures, morphologies, and mechanical properties
Authors: Fuchs Dominik A. H. , Hübner Hanna , Kraus Tobias , Niebuur Bart-Jan , Gallei Markus , Frey Holger , Müller Axel H. E.
Published: July 2021

Polar modifiers strongly affect the statistical anionic copolymerization of biobased β-myrcene with styrene, leading to a variety of morphologies.
High hydrogen release catalytic activity by quasi-MOFs prepared via post-synthetic pore engineering
Authors: Bagheri Minoo , Masoomi Mohammad Yaser , Domínguez Esther , García Hermenegildo
Published: July 2021

TMU-10 treated at 300 °C under air efficiently promotes H2 generation at ambient temperature from NaBH4. The enhanced catalytic activity derives from a higher density of Lewis acid sites and the generation of mesoporosity.
Evolution and diversification of the nuclear pore complex
Authors: Makarov Alexandr A. , Padilla-Mejia Norma E. , Field Mark C.
Published: July 2021

The nuclear pore complex (NPC) is responsible for transport between the cytoplasm and nucleoplasm and one of the more intricate structures of eukaryotic cells. Typically composed of over 300 polypeptides, the NPC shares evolutionary origins with endo-membrane and intraflagellar transport system complexes. The modern NPC was fully established by the time of the last eukaryotic common ancestor and, hence, prior to eukaryote diversification. Despite the complexity, the NPC structure is surprisingly flexible with considerable variation between lineages. Here, we review diversification of the NPC in major taxa in view of recent advances in genomic and structural characterisation of plant, protist and nucleomorph NPCs and discuss the implications for NPC evolution. Furthermore, we highlight these changes in the context of mRNA export and consider how this process may have influenced NPC diversity. We reveal the NPC as a platform for continual evolution and adaptation.
Quantitative neurogenetics: applications in understanding disease
Authors: Afrasiabi Ali , Keane Jeremy T. , Heng Julian Ik-Tsen , Palmer Elizabeth E. , Lovell Nigel H. , Alinejad-Rokny Hamid
Published: July 2021

Neurodevelopmental and neurodegenerative disorders (NNDs) are a group of conditions with a broad range of core and co-morbidities, associated with dysfunction of the central nervous system. Improvements in high throughput sequencing have led to the detection of putative risk genetic loci for NNDs, however, quantitative neurogenetic approaches need to be further developed in order to establish causality and underlying molecular genetic mechanisms of pathogenesis. Here, we discuss an approach for prioritizing the contribution of genetic risk loci to complex-NND pathogenesis by estimating the possible impacts of these loci on gene regulation. Furthermore, we highlight the use of a tissue-specificity gene expression index and the application of artificial intelligence (AI) to improve the interpretation of the role of genetic risk elements in NND pathogenesis. Given that NND symptoms are associated with brain dysfunction, risk loci with direct, causative actions would comprise genes with essential functions in neural cells that are highly expressed in the brain. Indeed, NND risk genes implicated in brain dysfunction are disproportionately enriched in the brain compared with other tissues, which we refer to as brain-specific expressed genes. In addition, the tissue-specificity gene expression index can be used as a handle to identify non-brain contexts that are involved in NND pathogenesis. Lastly, we discuss how using an AI approach provides the opportunity to integrate the biological impacts of risk loci to identify those putative combinations of causative relationships through which genetic factors contribute to NND pathogenesis.
Polymer models are a versatile tool to study chromatin 3D organization
Authors: Esposito Andrea , Bianco Simona , Fiorillo Luca , Conte Mattia , Abraham Alex , Musella Francesco , Nicodemi Mario , Prisco Antonella , Chiariello Andrea M.
Published: July 2021

The development of new experimental technologies is opening the way to a deeper investigation of the three-dimensional organization of chromosomes inside the cell nucleus. Genome architecture is linked to vital functional purposes, yet a full comprehension of the mechanisms behind DNA folding is still far from being accomplished. Theoretical approaches based on polymer physics have been employed to understand the complexity of chromatin architecture data and to unveil the basic mechanisms shaping its structure. Here, we review some recent advances in the field to discuss how Polymer Physics, combined with numerical Molecular Dynamics simulation and Machine Learning based inference, can capture important aspects of genome organization, including the description of tissue-specific structural rearrangements, the detection of novel, regulatory-linked architectural elements and the structural variability of chromatin at the single-cell level.
Phosphate and fibroblast growth factor 23 in diabetes
Authors: van der Vaart Amarens , Yeung Stanley M.H. , van Dijk Peter R. , Bakker Stephan J.L. , de Borst Martin H.
Published: July 2021

Diabetes is associated with a strongly elevated risk of cardiovascular disease, which is even more pronounced in patients with diabetic nephropathy. Currently available guideline-based efforts to correct traditional risk factors are only partly able to attenuate this risk, underlining the urge to identify novel treatment targets. Emerging data point towards a role for disturbances in phosphate metabolism in diabetes. In this review, we discuss the role of phosphate and the phosphate-regulating hormone fibroblast growth factor 23 (FGF23) in diabetes. We address deregulations of phosphate metabolism in patients with diabetes, including diabetic ketoacidosis. Moreover, we discuss potential adverse consequences of these deregulations, including the role of deregulated phosphate and glucose as drivers of vascular calcification propensity. Finally, we highlight potential treatment options to correct abnormalities in phosphate and FGF23. While further studies are needed to more precisely assess their clinical impact, deregulations in phosphate and FGF23 are promising potential target in diabetes and diabetic nephropathy.
A novel epigenetic drug conjugating flavonoid and HDAC inhibitor confer suppression of acute myeloid leukemogenesis
Authors: Zhang Juan , Gao Xuefeng , Wei Mingming , Li Yonghui , Yang Guang , Yang Cheng , Yu Li
Published: July 2021

Epigenetic dysregulation has long been identified as a key driver of leukemogenesis in acute myeloid leukemia (AML). However, epigenetic drugs such as histone deacetylase inhibitors (HDACis) targeting epigenetic alterations in AML have obtained only limited clinical efficiency without clear mechanism. Fortunately, we screened out a novel epigenetic agent named Apigenin–Vorinostat-Conjugate (AVC), which provides us a possibility to handle the heterogeneous malignancy. Its inhibition on HDACs was presented by HDACs expression, enzyme activity, and histone acetylation level. Its efficacy against AML was detected by cell viability assay and tumor progression of AML mouse model. Apoptosis is the major way causing cell death. We found that AVC efficiently suppresses leukemogenesis while sparing the normal human cells. Kasumi-1 cells are at least 20-fold higher sensitive to AVC (IC50 = 0.024 μM) than vorinostat (IC50 = 0.513 μM) and Ara-C (IC50 = 0.4366 μM). Furthermore, it can efficiently regress the tumorigenesis in AML mouse model while keeping the pivotal organs safe, demonstrating a feasibility and favorable safety profile in treatment of AML. Collectively, these preclinical data suggest a promising potential utilizing flavonoid–HDACi-conjugate as a next-generation epigenetic drug for clinical therapy against AML.
DNA-nanopore technology: a human perspective
Authors: Gray Alexander
Published: July 2021

The purpose of this article is to give a brief overview of the current state of nanopore sequencing in relation to forensic science with a brief outline of where it stands in relation to current methods, its potential uses in forensic science and factors which may influence acceptance of this technology by forensic practitioners, the judiciary and law enforcement. Perhaps most importantly consideration is also given to concerns which may influence the acceptance of the technology by the general public.
Aging Effect on Mandarin Chinese Vowel and Tone Identification in Six-Talker Babble
Authors: Liu Chang , Xu Can , Wang Yuxia , Xu Lilong , Zhang Hui , Yang Xiaohu
Published: July 2021

Purpose

The purpose of this study was to measure Mandarin Chinese vowel-plus-tone identification in quiet and noise for younger and older listeners.

Method

Two types of noise served as the masker, namely, six-talker babble and babble-modulated noise, at two signal-to-noise ratios (SNRs) of −4 and −8 dB. Fourteen listeners from both age groups were recruited, and three sets of data analyses were conducted: the identification of vowel plus tone, the identification of vowel, and the identification of tone.

Results

Younger listeners outperformed older listeners in all listening conditions, whereas the younger–older listener difference became greater in noise than in quiet, indicating a more detrimental effect of noise for older listeners than for younger listeners. In addition, vowel identification showed slightly better scores than tone identification in noise, suggesting that noise appeared to affect tone perception more negatively than vowel perception in Mandarin Chinese. At −4 dB SNR, there was a significantly greater amount of informational masking (IM) and a greater amount of energetic masking (EM) for older listeners than for younger listeners. At −8 dB SNR, there was a greater amount of EM for older listeners than for younger listeners but with no group difference in the amount of IM.

Conclusion

These results suggest that older listeners received a more negative impact of noise for Mandarin Chinese phonemic and tone recognition and had a larger amount of IM or EM from competing speech noise than younger listeners, depending on the SNR.
Design and analysis of a novel coupled converter with high‐voltage insulation protection in magnetic isolated way
Authors: Fu Ming , Zhang Donglai , Zhang Di , Zhang Xiantao
Published: July 2021

This paper presents a novel coupled converter with high‐voltage insulation protection in magnetic isolated way by taking the case of heater/ignitor/keeper supply for powering discharge cathode in the space ion electric propulsion (EP) thruster. The topology, working principle and igniting timing, as well as the adaptive closed‐loop control and heating‐igniting interlock control are also illustrated. For the proposed converter, the coupled topology and control strategy only adopt three straddling magnetic components to realize all functions. Meanwhile, the number of electronic components suspending over the high‐voltage side of beam supply is small enough. Additionally, the test on the coupled converter prototype shows that, the maximum efficiency is 88.6%, close to the traditional tightly coupled supply; the proposed converter could realize the function of heating/igniting/keeping for the discharge cathode under the magnetic isolated way and corresponding control strategy; and there is no “spark phenomenon” for the converter during low‐pressure discharge test. Hence, the magnetic isolated way to obtain the physical separation between high‐voltage and low‐voltage side in the converter is useful to achieve the high‐voltage insulation protection.
Radiative Rayleigh-Taylor instability and the structure of clouds in planetary atmospheres
Authors: Tremblin P. , Bloch H. , González M. , Audit E. , Fromang S. , Padioleau T. , Kestener P. , Kokh S.
Published: July 2021

Aims.Clouds are expected to form in a broad range of conditions in the atmosphere of exoplanets given the variety of possible condensible species. This diversity, however, might lead to very different small-scale dynamics depending on radiative transfer in various thermal conditions. Here, we aim to provide some insight into these dynamical regimes.

Methods.We performed an analytical linear stability analysis of a compositional discontinuity with a heating source term that depends on a given composition. We also performed idealized two-dimensional simulations of an opacity discontinuity in a stratified medium, using theARKcode. We used a two-stream gray model for radiative transfer and explored the brown-dwarf and Earth-like regimes.

Results.We revealed the existence of a radiative Rayleigh-Taylor instability (RRTI, hereafter, which is a particular case of diabatic Rayleigh-Taylor instability) when an opacity discontinuity is present in a stratified medium. This instability is similar in nature to diabatic convection and relies only on buoyancy with radiative transfer heating and cooling. When the temperature is decreasing with height in the atmosphere, a lower-opacity medium on top of a higher-opacity medium is shown to be dynamically unstable, whereas a higher-opacity medium on top of a lower-opacity medium is stable. This stability-instability behavior is reversed if the temperature is increasing with height.

Conclusions.The existence of a RRTI could have important implications for the stability of the cloud cover with regard to a wide range of planetary atmospheres. In our Solar System, it could help explain the formation of mammatus cloud in Earth atmospheres and the existence of the Venus cloud deck. Likewise, it suggests that stable and large-scale cloud covers could be ubiquitous in strongly irradiated exoplanets, but might be more patchy in low-irradiated or isolated objects such as brown dwarfs and directly imaged exoplanets.
(216) Kleopatra, a low density critically rotating M-type asteroid
Authors: Marchis F. , Jorda L. , Vernazza P. , Brož M. , Hanuš J. , Ferrais M. , Vachier F. , Rambaux N. , Marsset M. , Viikinkoski M. , Jehin E. , Benseguane S. , Podlewska-Gaca E. , Carry B. , Drouard A. , Fauvaud S. , Birlan M. , Berthier J. , Bartczak P. , Dumas C. , Dudziński G. , Ďurech J. , Castillo-Rogez J. , Cipriani F. , Colas F. , Fetick R. , Fusco T. , Grice J. , Kryszczynska A. , Lamy P. , Marciniak A. , Michalowski T. , Michel P. , Pajuelo M. , Santana-Ros T. , Tanga P. , Vigan A. , Witasse O. , Yang B.
Published: July 2021

Context. The recent estimates of the 3D shape of the M/Xe-type triple asteroid system (216) Kleopatra indicated a density of ~5 g cm−3, which is by far the highest for a small Solar System body. Such a high density implies a high metal content as well as a low porosity which is not easy to reconcile with its peculiar “dumbbell” shape.

Aims. Given the unprecedented angular resolution of the VLT/SPHERE/ZIMPOL camera, here, we aim to constrain the mass (via the characterization of the orbits of the moons) and the shape of (216) Kleopatra with high accuracy, hence its density.

Methods. We combined our new VLT/SPHERE observations of (216) Kleopatra recorded during two apparitions in 2017 and 2018 with archival data from the W. M. Keck Observatory, as well as lightcurve, occultation, and delay-Doppler images, to derive a model of its 3D shape using two different algorithms (ADAM, MPCD). Furthermore, an N-body dynamical model allowed us to retrieve the orbital elements of the two moons as explained in the accompanying paper.

Results. The shape of (216) Kleopatra is very close to an equilibrium dumbbell figure with two lobes and a thick neck. Its volume equivalent diameter (118.75 ± 1.40) km and mass (2.97 ± 0.32) × 1018 kg (i.e., 56% lower than previously reported) imply a bulk density of (3.38 ± 0.50) g cm−3. Such a low density for a supposedly metal-rich body indicates a substantial porosity within the primary. This porous structure along with its near equilibrium shape is compatible with a formation scenario including a giant impact followed by reaccumulation. (216) Kleopatra’s current rotation period and dumbbell shape imply that it is in a critically rotating state. The low effective gravity along the equator of the body, together with the equatorial orbits of the moons and possibly rubble-pile structure, opens the possibility that the moons formed via mass shedding.

Conclusions. (216) Kleopatra is a puzzling multiple system due to the unique characteristics of the primary. This system certainly deserves particular attention in the future, with the Extremely Large Telescopes and possibly a dedicated space mission, to decipher its entire formation history.
The most luminous blue quasars at 3.0 < z < 3.3
Authors: Lusso E. , Nardini E. , Bisogni S. , Risaliti G. , Gilli R. , Richards G. T. , Salvestrini F. , Vignali C. , Bargiacchi G. , Civano F. , Elvis M. , Fabbiano G. , Marconi A. , Sacchi A. , Signorini M.
Published: July 2021

We analyse the properties of the high-ionisation C IVλ1549 broad emission line in connection with the X-ray emission of 30 bright, optically selected quasars at z ≃ 3.0−3.3 with pointed XMM-Newton observations, which were selected to test the suitability of active galactic nuclei as cosmological tools. In our previous work, we found that a large fraction (≈25%) of the quasars in this sample are X-ray under-luminous by factors of > 3−10. As absorbing columns of ≳1023 cm−2 can be safely ruled out, their weakness is most likely intrinsic. Here we explore possible correlations between the UV and X-ray features of these sources to investigate the origin of X-ray weakness with respect to X-ray-normal quasars at similar redshifts. We fit the UV spectra from the Sloan Digital Sky Survey of the quasars in our sample and analyse their C IV properties – for example equivalent width (EW) and line peak velocity (υpeak) – as a function of the X-ray photon index and 2−10 keV flux. We confirm the statistically significant trends of C IVυpeak and EW with UV luminosity at 2500 Å for both X-ray-weak and X-ray-normal quasars, as well as the correlation between X-ray weakness (parametrised through Δαox) and C IV EW. In contrast to some recent work, we do not observe any clear relation between the 2−10 keV luminosity and υpeak. We find a statistically significant correlation between the hard X-ray flux and the integrated C IV flux for X-ray-normal quasars, which extends across more than three (two) decades in C IV (X-ray) luminosity, whilst X-ray-weak quasars deviate from the main trend by more than 0.5 dex. We argue that X-ray weakness might be interpreted in a starved X-ray corona picture associated with an ongoing disc-wind phase. If the wind is ejected in the vicinity of the black hole, the extreme-UV radiation that reaches the corona will be depleted, depriving the corona of seed photons and generating an X-ray-weak quasar. Nonetheless, at the largest UV luminosities (> 1047 erg s−1) there will still be an ample reservoir of ionising photons that can explain the ‘excess’ C IV emission observed in the X-ray-weak quasars with respect to normal sources of similar X-ray luminosities.
A calibration of the Rossby number from asteroseismology
Authors: Corsaro E. , Bonanno A. , Mathur S. , García R. A. , Santos A. R. G. , Breton S. N. , Khalatyan A.
Published: July 2021

Stellar activity and rotation are tightly related in a dynamo process. Our understanding of this mechanism is mainly limited by our capability of inferring the properties of stellar turbulent convection. In particular, the convective turnover time is a key ingredient through the estimation of the stellar Rossby number, which is the ratio of the rotation period and the convective turnover time. In this work, we propose a new calibration of the (B − V) color index dependence of the convective turnover time, hence, of the stellar Rossby number. Our new calibration is based on the stellar structure properties inferred through the detailed modeling of solar-like pulsators using asteroseismic observables. We show the impact of this calibration via a stellar activity-Rossby number diagram by applying it to a sample of about 40 000 stars observed with Kepler and for which the values for the photometric activity proxy S​ph and surface rotation periods are available. Additionally, we provide a new calibration for the convective turnover time as function of the (GBP − GRP) color index for allowing applicability in the ESA Gaia photometric passbands.
Decoding low-temperature thermochronology signals in mountain belts: modelling the role of rift thermal imprint into continental collision
Authors: Ternois Sébastien , Mouthereau Frédéric , Jourdon Anthony
Published: July 2021

Resolving the timing of initiation and propagation of continental accretion associated with increasing topography and exhumation is a genuinely challenging task using low-temperature thermochronology. We present an integrated thermo-mechanical and low-temperature thermochronology modelling study of tectonically-inverted hyperextended rift systems. Model low-temperature thermochronology data sets for apatite (U-Th)/He, apatite fission-track, zircon (U-Th)/He and zircon fission-track systems, which are four widely used thermochronometric systems in orogenic settings, are generated from fourteen locations across a model collisional, doubly-vergent orogen. Our approach allows prediction of specific, distinct low-temperature thermochronology signatures for each domain (proximal, necking, hyperextended, exhumed mantle) of the two rifted margins that, in turn, enable deciphering which parts of the margins are involved in orogenic wedge development. Our results show that a combination of zircon (U-Th)/He and apatite fission-track data allows diagnostic investigation of model orogen tectonics and offers the most valuable source of thermochronological information for the reconstruction of the crustal architecture of the model inverted rifted margins. The two thermochronometric systems have actually very close and wide closure windows, allowing to study orogenic processes over a larger temperature range, and therefore over a longer period of time. Comparison of model data for inverted rifted margins with model data for non-inverted, purely thermally-relaxed rifted margins enables assessing the actual contribution of tectonic inversion with respect to thermal relaxation. We apply this approach to one of the best-documented natural examples of inverted rift systems, the Pyrenees. Similarities between our thermochronometric modelling results and published low-temperature thermochronology data from the Pyrenees provide new insights into the evolution of the range from rifting to collision. In particular, they suggest that the core of the Pyrenean orogen, the Axial Zone, consists of the inverted lower plate necking and hyperextended domains while the Pyrenean retrowedge fold-and-thrust belt, the North Pyrenean Zone, represents the inverted upper plate distal rifted margin (exhumed mantle, hyperextended and necking domains). This is in good agreement with previous, independent reconstructions from literature, showing the power that our integrated study offers in identifying processes involved in orogenesis, especially early inversion, as well as in predicting which domains of rifted margins are accreted during mountain building.
Numerical analysis of a Reynolds Stress Model for turbulent mixing: the one-dimensional case
Authors: Blanc Xavier , Colavolpe Charles , Duclous Roland , Griffond Jérôme , Soulard Olivier
Published: July 2021

A mixed hyperbolic-parabolic, non conservative, Reynolds Stress Model (RSM), is studied. It is based on an underlying set of Langevin equations, and allows to describe turbulent mixing, including transient demixing effects as well as incomplete mixing. Its mathematical structure is analysed, and specific regimes, related to acoustic-like, Riemann-type, or self-similar solutions, are identified. A second-order accurate numerical scheme is proposed in arbitrary curvilinear geometry. Its accuracy and convergence behaviour are tested by comparison with analytical solutions in the different regimes. The numerical scheme can be generalized to multi-dimensional configurations, with potentially cylindrical symmetry, on unstructured meshes.