bluuebunny/crossref_metadata_2025 huggingface dataset:
Research on the linkage of dual servo motors based on electronic cam curves
Authors: Cui Jianjun , Zhang Yuhang , Lei Zhen , Fang Yuxuan , Li Chunfeng
Published: June 2022

For the servo dual motor linkage lag and large error problems, electronic cam curve planning is introduced. This servo system uses Microchip's MPLAB development platform and consists of a digital servo driver, two servo motors, etc. The servo motors use a vector control strategy. The position command of the slave servo motor is calculated according to the speed of the spindle motor and the electronic cam table, and the reciprocating motion of the motor pendulum is realised by simulating a mechanical cam, and the five-term and one-term curves are used to articulate with each other in the acceleration, uniform speed and deceleration stages. The experimental results show that with the electronic cam scheme, the servo system combines the advantages of high response speed and high control accuracy, while the curve planning and parameters are easy to adjust and meet the requirements of industrial production.
Comparative analysis of modulation strategies of bidirectional isolated AC-DC Matrix Converter
Authors: Liu Jinglin
Published: June 2022

Bidirectional isolated AC-DC matrix converter is a new topology which has potential advantages in many aspects. But the topology of bidirectional isolated AC-DC matrix converter is complex, the front and rear circuits are coupled and interact with each other, it is difficult to decouple it directly, and it is difficult to modulate. So it is necessary to study its modulation strategy. In this paper, several existing modulation strategies are analysed and compared from three aspects: switching process, current stress and transmission power, and a relatively optimal modulation strategy is obtained. The superiority and correctness of the modulation strategy are verified by simulation.
Nonlinear rendezvous guidance law design for a receiver UAV based on the Lyapunov stability theory
Authors: Zhao Hongchao , Zhao Jianzhong , Xu Hongmei
Published: June 2022

The rendezvous problem in the autonomous aerial refueling (AAR) was researched for the receiver unmanned aerial vehicle (UAV). The three-dimensional guidance model was constructed for the UAV to pursue the virtual tanker. In order to guarantee the zero miss distance and the intercept angle constraints, a nonlinear rendezvous guidance law was designed for the UAV based on the Lyapunov stability theory. The guidance law generated the normal acceleration command and the lateral acceleration command. The velocity control system was designed by the sliding mode control method. It controled the UAV’s velocity to equal to that of the virtual tanker at the end of the rendezvous phase. The simulation results validate the effectiveness of the designed nonlinear guidance law and the velocity control system.
Sliding mode disturbance observer and sliding mode controller for quadrotor UAV
Authors: Chen Jie , Zhao Hongchao
Published: June 2022

The dynamics of quadrotor UAV is described considering internal uncertainty and external disturbance. The control system of quadrotor UAV is divided into inner loop attitude control system and outer loop position control system, In order to solve the problem of underactuated character. Three virtual control variables are introduced to decouple the position dynamics. Three sliding mode disturbance observers (SMDOs) are designed to estimate the total disturbances in the position dynamics. Then three sliding mode controllers (SMCs) are designed to drive the trajectory tracking errors to zero asymptotically. The simulation example is carried out to test the effectiveness of SMDOs and SMCs. Simulation results validate that the designed SMDOs and SMCs provide both fast exact tracking capability and strong disturbance rejection capability for the quadrotor UAV.
Upgrade of the CMD-3 trigger system
Authors: Gorkovenko A.O. , Epshteyn L.B. , Yudin Y.V. , Talyshev A.A.
Published: June 2022

In 2017, the luminosity at the VEPP-2000 collider at the Budker Institute of Nuclear Physics SB RAS, Novosibirsk, was increased. This required an upgrade of the L-1 trigger to improve system performance and stability while reducing latency. In addition, the existing L-1 trigger firmware blocks are outdated and do not meet the new requirements. For this, the development of a device called the decision block will be created. The task of this unit is to generate the decision on whether to record the current event. In this paper, we present the stages of upgrading the L-1 trigger, the decision block design and implementation.
Development of a single-photon imaging detector with pixelated anode and integrated digital read-out
Authors: Alozy J.A. , Biesuz N.V. , Campbell M. , Cavallini V. , Cotta Ramusino A. , Fiorini M. , Guarise M. , Llopart Cudie X.
Published: June 2022

We present the development of a single-photon detector and the connected read-out electronics. This “hybrid” detector is based on a vacuum tube, transmission photocathode, microchannel plate and a pixelated CMOS read-out anode encapsulating the analog and digital-front end electronics. This assembly will be capable of detecting up to 109 photons per second with simultaneous measurement of position and time.

The pixelated read-out anode used is based on the Timepix4 ASIC (65 nm CMOS technology) designed in the framework of the Medipix4 collaboration. This ASIC is an array of 512 × 448 pixels distributed on a 55 μm square pitch, with a sensitive area of  ∼7 cm2. It features 50–70 e− equivalent noise charge, a maximum rate of 2.5 Ghits/s, and allows to time-stamp the leading-edge time and to measure the Time-over-Threshold (ToT) for each pixel. The pixel-cluster position combined with its ToT information will allow to reach 5–10 μm position resolution. This information can also be used to correct for the leading-edge time-walk achieving a timing resolution of the order of 10 ps.

The detector will be highly compact thanks to the encapsulated front-end electronics allowing local data processing and digitization. An FPGA-based data acquisition board, placed far from the detector, will receive the detector hits using 16 electro-optical links operated at 10.24 Gbps. The data acquisition board will decode the information and store the relevant data in a server for offline analysis.

These performance will allow significant advances in particle physics, life sciences, quantum optics or other emerging fields where the detection of single photons with excellent timing and position resolutions are simultaneously required.
Motion mechanism and thrust characteristics of amphibious robots with long fin fluctuation for propulsion on hard level ground
Authors: Zhang Jian , Zhou Junjie , Yuan Shihua , Jing Chongbo
Published: June 2022

This paper presents the principle of motion, mechanical modeling and key characteristics of the propulsive force of a new flexible-fin traveling wave propulsion mechanism used in an amphibious robot. Firstly, the form of motion and the basic propulsion principle of traveling wave propulsion of flexible fins on the ground are described. During fluctuation of the flexible fins, the relative motion between the outermost contact line on the fin surface and the ground generates the propulsive force of forward motion and the lateral force along the fin surface. Based on the laws of flexible-fin fluctuation kinematics and the basic principles of friction mechanics, the propulsion mechanics model of flexible fins during traveling wave propulsion on the ground is established. By numerically solving the propulsive force equation, the relationship between the propulsive force of the flexible fin and the motion parameters of the fin surface can be obtained. Numerical calculations combined with the results of experimental tests reveal that the flexible-fin propulsive force shows periodic variations within one fluctuation period of the fin surface, and the variation period is related to the number of waves present on the fin surface. The wavenumber on the fin surface has a large impact on the fluctuation amplitude of the propulsive force. In the range of 1.6–1.9 waves on the fin surface, the average propulsive force is the most ideal, while in the range of fin-surface inclinations less than 50° and fluctuation amplitudes greater than 30°, the propulsive force of the flexible fin is the ideal parameter range. This research provides theoretical support for the design of a flexible-fin traveling wave propulsion mechanism.
New insight into the influence of the Greenland high on summer Arctic sea ice
Authors: Wang Shaoyin , Liu Jiping , Li Xinyu , Ye Yufang , Greatbatch Richard J , Chen Zhuoqi , Cheng Xiao
Published: June 2022

The Greenland high (GL-high) coincides with a local center of action of the summer North Atlantic Oscillation and is known to have significant influence on Greenland ice sheet melting and summer Arctic sea ice. However, the mechanism behind the influence on regional Arctic sea ice is not yet clear. In this study, using reanalysis datasets and satellite observations, the influence of the GL-high in early summer on Arctic sea ice variability, and the mechanism behind it, are investigated. In response to an intensified GL-high, sea ice over the Beaufort Sea shows significant decline in both concentration and thickness from June through September. This decline in sea ice is primarily due to thermodynamic and mechanical redistribution processes. Firstly, the intensified GL-high increases subsidence over the Canadian Basin, leading to an increase in surface air temperature by adiabatic heating, and a substantial decrease in cloud cover and thus increased downward shortwave radiation. Secondly, the intensified GL-high increases easterly wind frequency and wind speed over the Beaufort Sea, pushing sea ice over the Canadian Basin away from the coastlines. Both processes contribute to an increase in open water areas, amplifying ice–albedo feedback and leading to sea ice decline. The mechanism identified here differs from previous studies that focused on northward moisture and heat transport and the associated increase in downward longwave radiation over the Arctic. The impact of the GL-high on the regional sea ice (also Arctic sea ice extent) can persist from June into fall, providing an important source for seasonal prediction of Arctic sea ice. The GL-high has an upward trend and reached a record high in 2012 that coincided with a record minimum summer Arctic sea ice extent, and has strong implications for summer Arctic sea ice changes.
Conditioning two diffusion processes with respect to their first-encounter properties
Authors: Mazzolo Alain , Monthus Cécile
Published: June 2022

We consider two independent identical diffusion processes that annihilate upon meeting in order to study their conditioning with respect to their first-encounter properties. For the case of finite horizon T < +∞, the maximum conditioning consists in imposing the probability P*(x, y, T) that the two particles are surviving at positions x and y at time T, as well as the probability γ*(z, t) of annihilation at position z at the intermediate times t ∈ [0, T]. The adaptation to various conditioning constraints that are less-detailed than these full distributions is analyzed via the optimization of the appropriate relative entropy with respect to the unconditioned processes. For the case of infinite horizon T = +∞, the maximum conditioning consists in imposing the first-encounter probability γ*(z, t) at position z at all finite times

t
∈

0
,
+
∞

, whose normalization [1 − S*(∞)] determines the conditioned probability S*(∞) ∈ [0, 1] of forever-survival. This general framework is then applied to the explicit cases where the unconditioned processes are respectively two Brownian motions, two Ornstein–Uhlenbeck processes, or two tanh-drift processes, in order to generate stochastic trajectories satisfying various types of conditioning constraints. Finally, the link with the stochastic control theory is described via the optimization of the dynamical large deviations at level 2.5 in the presence of the conditioning constraints that one wishes to impose.
Life Cycle Cost Analysis of Local Rice Production in Bangka Regency, Indonesia
Authors: Supriyanto  , Solahudin Mohamad , Aprilia Dea
Published: June 2022

Rice is the main staple food for Indonesian people and produced in every Island in Indonesia. Rice production are consisting of several activities such as: cultivation by farmers, processed in milling factory, post-harvest, and selling to the customers. Cost calculation for overall production process are important for cost evaluation in every rice production. The aim of this research was to use life cycle cost analysis for rice production scenario for two cultivars (Mapan 05 and Inpari 32) in Bangka Regency, Indonesia. Life cycle cost scenario was used in this research was 240 scenarios with three main production scenario such as: production with mechanization, production with semi-mechanization, and production with manual (local technology). Rice Production stages was set as system boundary that consist of (1) land preparation, (2) cultivation, and (3) post-harvest to produce white rice. The result of this study was the lowest LCC was IDR 5,765.72 kg-1 and IDR 6,237.97 kg-1 for Mapan 05 and Inpari 32 cultivars.
Utilization of anaerobically digested dairy manure wastewater for Spirulina maxima cultivation
Authors: Rahman D Y , Hidhayati N , Apriastini M , Taufikurahman
Published: June 2022

Microalgae have attracted the attention of scientists as microalgae have been considered as having higher productivities than terrestrial plants. Microalgae can be used to produce several valuable commodities such as bioenergy, feed, and food. Combining the growth medium with wastewater can enhance the economic feasibility of microalgae-based products. In this research, Spirulina maxima were cultivated using bioslurry from anaerobically digested dairy manure wastewater (ADDMW) at concentrations 0, 50, and 100 %. The growth curve was monitored by measuring the dry weight of microalgae every three days. The results showed that the S. maxima growth in ADDMW showed no difference from S. maxima growth in Zarrouk medium (2.090 g L-1 and 1.933 g L-1, respectively). Phycocyanin, one of the primary pigments of S. maxima, was determined to evaluate the effect of wastewater medium on phycocyanin production. The phycocyanin content of S. maxima in 0, 50, and 100 % wastewater showed no difference (58.67, 56.51, and 54.67 mg L-1 culture, respectively). This study provides an insight into the potential use of ADDMW as a substitute of growth medium of S. maxima as it supported the growth and phycocyanin production, with the result similar to when using the commercial medium.
UV spectral analysis coupled with PCA-LDA to classify organic and conventional Lampung robusta coffee from different origins
Authors: Yulia M , Suhandy D
Published: June 2022

This current research presents a simple analytical method for classifying organic and conventional coffee samples from different origins. UV pre-processed spectral data in the range of 250-400 nm was used to discriminate between organic Lampung robusta coffee from Lampung Barat (n=50) and two conventional Lampung robusta coffees from Lampung Barat (n=50) and Tanggamus (n=50). Ground roasted coffee samples with 50 mesh were used for samples. UV-vis spectrometer was utilized to acquire UV spectral data from an aqueous coffee sample. A chemometric method based on PCA and PCA-LDA algorithm was used to classify the samples. The PCA result shows all organic coffee samples were clustered on the negative of PC1 while all conventional coffee samples were on the positive of PC1. The conventional coffee samples from Lampung Barat and Tanggamus were grouped in different clusters according to their origin. The PCA-LDA resulted in a 100% accuracy in classification both for calibration and prediction. This method is a promising approach for organic Lampung robusta authentication with a relatively low-cost spectrometer and simple sample preparation.
Using sentinel and comparing two classification algorithms for land cover mapping in the area dominated by small scale heterogeneous agricultural land
Authors: Rahayu Chairiyah Umi , Indarto Indarto , Cahyono Bowo Eko
Published: June 2022

Sentinel images are widely used for monitoring and mapping our environment phenomenon. The imagery applies in land-use and land cover mapping using pixel-based classification, image segmentation, or other image interpretation algorithms. One type of algorithm may be more suitable for a specific area, depending on many factors. This study aims to analyse and compare two classification algorithms for land cover (LC) mapping in the region characterised by a small scale type of agricultural land occupation. The primary input for this study is the Sentinel 2A image. Two well-known pixel-based classification algorithms, i.e., Maximum Likelihood classifier (MLC) and ECHO (Extraction and Classification of Homogeneous Objects), are used and are compared. The study covers an area of 3320.3 km2. The classification result produces nine (9) land cover classes, i.e., (1) pavement or urban area, (2) heterogeneous agricultural land, (3) irrigated paddy, (4) open water body, (5) dense vegetation or forest, (6) sparse vegetation or plantation, (7) shrubland or dry-land, (8) wetlands, and (9) sand-clay-rock. Classification using MLC and ECHO produced kappa and overall accuracies of more than 90%. In general, both algorithms can produce a relatively similar area extend for each class. However, two classes, i.e., (2) heterogeneous agricultural land and (6) sparse vegetation, are still tricky to distinguish.
Abnormal Shapes Identification of Gedong Mango Using Dimensionless Shape Factors in Image Processing
Authors: Ahmad U , Rosyid Muadz A. , Mardison
Published: June 2022

In addition to size, export quality requirements for gedong mango among others are clean surface, free of damaged mechanically or biologically, free from pests and diseases, and normal fruit shape. The abnormal fruit shape in mangoes is known as sitting mango, which is not easy to roll over when pushed because the fruit surface is flat on certain sides. Several dimensionless shape factors can be used to identify the shape of an object through image processing. Some shape factors that are often used to identify shapes of object in image processing include roundness, roundness ratio, sphericity, axial ratio, inequality degree of projected area and spherical disproportion. This study aims to identify the shape of the fruit using several dimensionless shape factors and determine the shape factors that can be used to distinguish normal and abnormal fruit shapes for gedong mangoes. The results showed that abnormal and normal mango gedong fruit shapes could be distinguished by image processing using the roundness, sphericity, and spherical disproportion form factors in certain deviant shapes but not for all samples.
Mapping and Assessing Black Pepper Growth using Time Series and Ground Data: A Case Study for Small Scale Cultivation in Bintulu, Sarawak
Authors: Zainol W N Z , Kamsan S Z L , Che’Ya N N
Published: June 2022

Mapping of crop cultivation using remote sensing immensely facilitate crop management and prediction. The capability to provide informative data enables users to monitor and manage their crops with optimum expenditure. Hence, this study was purposed on black pepper farm to establish an informative map of black pepper farm (SF, TF) in Sungai Plan, Bintulu, Sarawak using Landsat 8 OLI time series and ground truth data. Images from Landsat 8 OLI were retrieved and images were classified using Support Vector Machine (SVM). Extraction of farmland elevations was produced using black pepper points collected and processed through ArcGIS 10.4 software. Black pepper growth was measured through the percentage of height and DBH developed throughout this study. It was identified in this study that; (1) mapping black pepper farm using Landsat 8 OLI and SVM provides overall accuracy >70% and Kappa Coefficient >60% and, (2) the optimum black pepper growth was observed at elevation range between 39m - 50m. This study demonstrated that detailed information on geography and black pepper growth can enhance black pepper productivity and management.
Characterization of The Yield and Quality of Patchouli Oil Based on The Size of Chopping and Drying Type
Authors: Lubis A , Mandang T , Hermawan W , Sutrisno
Published: June 2022

One of the factors that affect the low yield and quality of patchouli oil is the way of handling raw materials. The purpose of this study was to examine the effect of drying type and chopping size on the yield and quality of patchouli oil. The method used in this research was experimental with descriptive analysis using two factors, namely the chopping size and the drying type. The results showed that the difference in the size of the chopped and the type of drying had a significant effect on the yield of patchouli oil, while the quality had an effect and no effect. Based on the analysis of the yield and quality of patchouli oil, the best treatment obtained in this study was the condition of chopping size 7 cm followed by drying (R1P1). The yield value of patchouli oil obtained in the R1P1 treatment is the highest yield of 2.55 % with yellow oil, specific gravity 0.973 g/g, solubility in alcohol 1:1, ester number 8.48 ml/g, refractive index 1.508°, patchouli alcohol 31.31 % are in accordance with SNI standards while the optical rotation -44.50°, and the acid number of 23.9 ml/g are not according to the SNI standard.
MPZL1 upregulation promotes tumor metastasis and correlates with unfavorable prognosis in non-small cell lung cancer
Authors: Feng Jian , Ouyang Huiling , Wang Jing , Pan Deshen , Sheng Luoyan , Xu Chaoliang , Lin Weihong , Hu Dingzhong , Chang Cheng , Jia Deshui
Published: June 2022

Non-small cell lung cancer (NSCLC), accounting for 85% of all lung cancer, is one of the leading causes of cancer-related death worldwide. Previously, we demonstrated that MPZL1 gene amplification promotes liver cancer metastasis through activating Src/Cortactin pathway. However, the clinical relevance and biological roles of the MPZL1 gene in lung cancer are still unknown. Here, we found that MPZL1 expression upregulates in human NSCLC, which is partly due to the copy number amplification of this gene. Next, we observed that high MPZL1 expression correlates with unfavorable prognosis of NSCLC patients. We further demonstrated that ectopic MPZL1 overexpression promotes in vitro migratory but not proliferation and colony formation abilities of both H1299 and H460 cells. Consistently, we found that MPZL1 knockdown impairs the migratory abilities of A549 and H1775 cells. Moreover, we found that MPZL1 knockdown inhibits in vivo metastatic but not tumor growth abilities of the A549 cells. Additionally, a total of 297 differentially expressed genes (DEGs) were identified by RNA sequencing in A549 cells upon MPZL1 knockdown. By integrative analysis of DEGs regulated by MPZL1 in A549 cells and human NSCLC tissues, we revealed that COL11A1 is the potential effector gene that positively regulated by MPZL1 and correlates with poor prognosis of NSCLC patients. In conclusion, our work indicates that one of the mechanisms by which MPZL1 promotes NSCLC metastasis is through upregulating the COL11A1, and MPZL1 can be used as a biomarker to predict the prognosis of NSCLC patients.
Elucidation of the genetic causes of bicuspid aortic valve disease
Authors: Gehlen Jan , Stundl Anja , Debiec Radoslaw , Fontana Federica , Krane Markus , Sharipova Dinara , Nelson Christopher P , Al-Kassou Baravan , Giel Ann-Sophie , Sinning Jan-Malte , Bruenger Christopher M H , Zelck Carolin F , Koebbe Laura L , Braund Peter S , Webb Thomas R , Hetherington Simon , Ensminger Stephan , Fujita Buntaro , Mohamed Salah A , Shrestha Malakh , Krueger Heike , Siepe Matthias , Kari Fabian Alexander , Nordbeck Peter , Buravezky Larissa , Kelm Malte , Veulemans Verena , Adam Matti , Baldus Stephan , Laugwitz Karl-Ludwig , Haas Yannick , Karck Matthias , Mehlhorn Uwe , Conzelmann Lars Oliver , Breitenbach Ingo , Lebherz Corinna , Urbanski Paul , Kim Won-Keun , Kandels Joscha , Ellinghaus David , Nowak-Goettl Ulrike , Hoffmann Per , Wirth Felix , Doppler Stefanie , Lahm Harald , Dreßen Martina , von Scheidt Moritz , Knoll Katharina , Kessler Thorsten , Hengstenberg Christian , Schunkert Heribert , Nickenig Georg , Nöthen Markus M , Bolger Aidan P , Abdelilah-Seyfried Salim , Samani Nilesh J , Erdmann Jeanette , Trenkwalder Teresa , Schumacher Johannes
Published: June 2022

Aims

The present study aims to characterize the genetic risk architecture of bicuspid aortic valve (BAV) disease, the most common congenital heart defect.

Methods and results

We carried out a genome-wide association study (GWAS) including 2236 BAV patients and 11 604 controls. This led to the identification of a new risk locus for BAV on chromosome 3q29. The single nucleotide polymorphism rs2550262 was genome-wide significant BAV associated (P = 3.49 × 10−08) and was replicated in an independent case–control sample. The risk locus encodes a deleterious missense variant in MUC4 (p.Ala4821Ser), a gene that is involved in epithelial-to-mesenchymal transformation. Mechanistical studies in zebrafish revealed that loss of Muc4 led to a delay in cardiac valvular development suggesting that loss of MUC4 may also play a role in aortic valve malformation. The GWAS also confirmed previously reported BAV risk loci at PALMD (P = 3.97 × 10−16), GATA4 (P = 1.61 × 10−09), and TEX41 (P = 7.68 × 10−04). In addition, the genetic BAV architecture was examined beyond the single-marker level revealing that a substantial fraction of BAV heritability is polygenic and ∼20% of the observed heritability can be explained by our GWAS data. Furthermore, we used the largest human single-cell atlas for foetal gene expression and show that the transcriptome profile in endothelial cells is a major source contributing to BAV pathology.

Conclusion

Our study provides a deeper understanding of the genetic risk architecture of BAV formation on the single marker and polygenic level.
Implantable defibrillators in primary prevention of genetic arrhythmias. A shocking choice?
Authors: Corrado Domenico , Link Mark S , Schwartz Peter J
Published: June 2022

Many previously unexplained life-threatening ventricular arrhythmias and sudden cardiac deaths (SCDs) in young individuals are now recognized to be genetic in nature and are ascribed to a growing number of distinct inherited arrhythmogenic diseases. These include hypertrophic cardiomyopathy, arrhythmogenic cardiomyopathy, long QT syndrome, Brugada syndrome, catecholaminergic polymorphic ventricular tachycardia (VT), and short QT syndrome. Because of their lower frequency compared to coronary disease, risk factors for SCD are not very precise in patients with inherited arrhythmogenic diseases. As randomized studies are generally non-feasible and may even be ethically unjustifiable, especially in the presence of effective therapies, the risk assessment of malignant arrhythmic events such as SCD, cardiac arrest due to ventricular fibrillation (VF), appropriate implantable cardioverter defibrillator (ICD) interventions, or ICD therapy on fast VT/VF to guide ICD implantation is based on observational data and expert consensus. In this document, we review risk factors for SCD and indications for ICD implantation and additional therapies. What emerges is that, allowing for some important differences between cardiomyopathies and channelopathies, there is a growing and disquieting trend to create, and then use, semi-automated systems (risk scores, risk calculators, and, to some extent, even guidelines) which then dictate therapeutic choices. Their common denominator is a tendency to favour ICD implantation, sometime with reason, sometime without it. This contrasts with the time-honoured approach of selecting, among the available therapies, the best option (ICDs included) based on the clinical judgement for the specific patient and after having assessed the protection provided by optimal medical treatment.
Serine biosynthesis as a novel therapeutic target for dilated cardiomyopathy
Authors: Perea-Gil Isaac , Seeger Timon , Bruyneel Arne A N , Termglinchan Vittavat , Monte Emma , Lim Esther W , Vadgama Nirmal , Furihata Takaaki , Gavidia Alexandra A , Arthur Ataam Jennifer , Bharucha Nike , Martinez-Amador Noel , Ameen Mohamed , Nair Pooja , Serrano Ricardo , Kaur Balpreet , Feyen Dries A M , Diecke Sebastian , Snyder Michael P , Metallo Christian M , Mercola Mark , Karakikes Ioannis
Published: June 2022

Aims

Genetic dilated cardiomyopathy (DCM) is a leading cause of heart failure. Despite significant progress in understanding the genetic aetiologies of DCM, the molecular mechanisms underlying the pathogenesis of familial DCM remain unknown, translating to a lack of disease-specific therapies. The discovery of novel targets for the treatment of DCM was sought using phenotypic sceening assays in induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) that recapitulate the disease phenotypes in vitro.

Methods and results

Using patient-specific iPSCs carrying a pathogenic TNNT2 gene mutation (p.R183W) and CRISPR-based genome editing, a faithful DCM model in vitro was developed. An unbiased phenotypic screening in TNNT2 mutant iPSC-derived cardiomyocytes (iPSC-CMs) with small molecule kinase inhibitors (SMKIs) was performed to identify novel therapeutic targets. Two SMKIs, Gö 6976 and SB 203580, were discovered whose combinatorial treatment rescued contractile dysfunction in DCM iPSC-CMs carrying gene mutations of various ontologies (TNNT2, TTN, LMNA, PLN, TPM1, LAMA2). The combinatorial SMKI treatment upregulated the expression of genes that encode serine, glycine, and one-carbon metabolism enzymes and significantly increased the intracellular levels of glucose-derived serine and glycine in DCM iPSC-CMs. Furthermore, the treatment rescued the mitochondrial respiration defects and increased the levels of the tricarboxylic acid cycle metabolites and ATP in DCM iPSC-CMs. Finally, the rescue of the DCM phenotypes was mediated by the activating transcription factor 4 (ATF4) and its downstream effector genes, phosphoglycerate dehydrogenase (PHGDH), which encodes a critical enzyme of the serine biosynthesis pathway, and Tribbles 3 (TRIB3), a pseudokinase with pleiotropic cellular functions.

Conclusions

A phenotypic screening platform using DCM iPSC-CMs was established for therapeutic target discovery. A combination of SMKIs ameliorated contractile and metabolic dysfunction in DCM iPSC-CMs mediated via the ATF4-dependent serine biosynthesis pathway. Together, these findings suggest that modulation of serine biosynthesis signalling may represent a novel genotype-agnostic therapeutic strategy for genetic DCM.
Efficacy and safety of a novel cryoballoon ablation system: multicentre comparison of 1-year outcome
Authors: Knecht Sven , Sticherling Christian , Roten Laurent , Badertscher Patrick , Krisai Philipp , Chollet Laurève , Küffer Thomas , Spies Florian , Völlmin Gian , Madaffari Antonio , Mühl Aline , Baldinger Samuel H , Servatius Helge , Tanner Hildegard , Osswald Stefan , Reichlin Tobias , Kühne Michael
Published: June 2022

Aims

The aim of the study was to compare the 1-year efficacy and safety of a novel cryoballoon (NCB) ablation system (POLARx; Boston Scientific) for pulmonary vein isolation (PVI) compared with the standard cryoballoon (SCB) system (Arctic Front, Medtronic).

Methods and results

Consecutive patients with atrial fibrillation (AF) undergoing PVI using the NCB and the SCB at two centres were included. We report 1-year efficacy after 12 months, short-term safety and hospitalizations within the blanking period, and predictors for AF recurrence. In case of repeat procedures, pulmonary vein (PV) reconnection patterns were characterized. Eighty patients (age 66 ± 10 years, ejection fraction 57 ± 10%, left atrial volume index 39 ± 13 mL/m2, paroxysmal AF in 64%) were studied. After a single procedure and a follow-up of 12 months, 68% in the NCB group and 70% in the SCB group showed no recurrence of AF/atrial tachycardias (P = 0.422). One patient in the NCB group suffered a periprocedural stroke with full recovery. There were no differences regarding hospitalizations during follow-up between the groups. PV reconnection observed during 12 repeat procedures (4 NCB, 8 SCB) pattern was comparable between the groups with more reconnections in the right-sided compared with the left-sided PVs.

Conclusion

In this multicentre study comparing two currently available cryoballoon ablation systems for PVI, no differences were observed in the efficacy and safety during a follow-up of 12 months.
Co-production of knowledge and strategies to support climate resilient fisheries
Authors: Mills Katherine E , Armitage Derek , Eurich Jacob G , Kleisner Kristin M , Pecl Gretta T , Tokunaga Kanae
Published: June 2022

Knowledge co-production offers a promising approach to design effective and equitable pathways to reach development goals. Fisheries Strategies for Changing Oceans and Resilient Ecosystems by 2030 (FishSCORE), a United Nations Ocean Decade programme, will co-produce knowledge that advances solutions for climate resilient fisheries through networks and partnerships that include scientists, stakeholders, practitioners, managers, and policy experts. FishSCORE will establish (1) a global network that will develop broadly relevant information and tools to assess and operationalize climate resilience in marine fisheries and (2) local and regional partnerships that will apply those tools to identify and forward context-specific resilience strategies. FishSCORE's activities will be guided by a set of core principles that include commitments to inclusivity, equity, co-leadership, co-ownership, and reciprocity. FishSCORE will focus on identifying solutions for climate resilient fisheries, and it will also advance goals associated with capacity, power, and agency that will support iterative, pluralistic approaches to decision-making in fisheries experiencing ongoing climate-driven changes. This process of co-producing knowledge and strategies requires considerable investments of time from all partners, which is well aligned with the Ocean Decade. However, secure funding must be prioritized to support and implement co-production activities over this long time horizon.
Clinicopathological characteristics and prognosis of resectable lung adenosquamous carcinoma: a population-based study of the SEER database
Authors: Wang Tengyong , Zhou Jian , Wang Yaxin , Zheng Quan , Lin Zhangyu , Li Guangchen , Mei Jiandong , Liu Lunxu
Published: June 2022

Objective

Adenosquamous carcinoma is a rare subtype of non-small cell lung cancer characterized by aggressive behavior, with combination of adenocarcinoma and squamous cell carcinoma components. The clinicopathological characteristics and prognosis of resectable adenosquamous carcinoma are incompletely understood and this study aimed to depict those in a large population.

Methods

A total of 805 adenosquamous carcinoma, 7875 squamous cell carcinoma and 23 957 adenocarcinoma patients who underwent lobectomy or sublobectomy were queried from the Surveillance, Epidemiology, and End Results database (2010–17). Clinicopathological characteristics of adenosquamous carcinoma patients were compared with those of squamous cell carcinoma and adenocarcinoma patients. Prognostic factors were identified by univariable and multivariable Cox regression analyses. Propensity score matching was applied to reduce confounding effects.

Results

Adenosquamous carcinoma was associated with higher pleural invasion incidence and poorer differentiation compared with squamous cell carcinoma or adenocarcinoma (P values < 0.001). The independent risk factors of cancer-specific survival of adenosquamous carcinoma patients were increasing age, male sex, invading through visceral pleura, poor differentiation and higher stage. Stage IB adenosquamous carcinoma patients whose tumor invaded through visceral pleura had significantly worse survival than those not (P = 0.003). Adenosquamous carcinoma patients had worse survival compared with squamous cell carcinoma (5-year-survival: 64.55 vs. 69.09%, P = 0.003) and adenocarcinoma (5-year-survival: 64.55 vs. 76.79%, P < 0.001) patients before match. And this difference persisted after match.

Conclusions

Resectable adenosquamous carcinoma patients had higher pleural invasion incidence, poorer differentiation and worse survival compared with squamous cell carcinoma and adenocarcinoma patients. Visceral pleural invasion status and differentiation grade were vital prognostic factors of adenosquamous carcinoma patients on the basis of stage.
Melatonin enhances stress tolerance in pigeon pea by promoting flavonoid enrichment, particularly luteolin in response to salt stress
Authors: Song Zhihua , Yang Qing , Dong Biying , Li Na , Wang Mengying , Du Tingting , Liu Ni , Niu Lili , Jin Haojie , Meng Dong , Fu Yujie
Published: June 2022

Melatonin improves plant resistance to multiple stresses by participating in the biosynthesis of metabolites. Flavonoids are an important family of plant secondary metabolites and are widely recognized to be involved in resistance; however, the crosstalk between melatonin and flavonoid is largely unknown. We found that the resistance of pigeon pea (Cajanus cajan) to salt, drought, and heat stresses were significantly enhanced by pre-treatment with melatonin. Combined transcriptome and LC-ESI-MS/MS metabolomics analyses showed that melatonin significantly induced the enrichment of flavonoids and mediated the reprogramming of biosynthetic pathway genes. The highest fold-increase in expression in response to melatonin treatment was observed for the CcF3´H family, which encodes an enzyme that catalyses the biosynthesis of luteolin, and the transcription factor CcPCL1 directly bonded to the CcF3´H-5 promoter to enhance its expression. In addition, salt stress also induced the expression of CcPCL1 and CcF3´H-5, and their overexpression in transgenic plants greatly enhanced salt tolerance by promoting the biosynthesis of luteolin. Overall, our results indicated that pre-treatment of pigeon pea with melatonin promoted luteolin biosynthesis through the CcPCL1 and CcF3´H-5 pathways, resulting in salt tolerance. Our study shows that melatonin enhances plant tolerance to multiple stresses by mediating flavonoid biosynthesis, providing new avenues for studying the crosstalk between melatonin and flavonoids.
Evidence for a moderate spin from X-ray reflection of the high-mass supermassive black hole in the cluster-hosted quasar H1821+643
Authors: Sisk-Reynés Júlia , Reynolds Christopher S , Matthews James H , Smith Robyn N
Published: June 2022

We present an analysis of deep Chandra Low-Energy and High-Energy Transmission Grating archival observations of the extraordinarily luminous radio-quiet quasar H1821+643, hosted by a rich and massive cool-core cluster at redshift z = 0.3. These data sets provide high-resolution spectra of the AGN at two epochs, free from contamination by the intracluster medium and from the effects of photon pile-up, providing a sensitive probe of the iron-K band. At both epochs, the spectrum is well described by a power-law continuum plus X-ray reflection from both the inner accretion disc and cold, slowly moving distant matter. Adopting this framework, we proceed to examine the properties of the inner disc and the black hole spin. Using Markov chain Monte Carlo (MCMC) methods, we combine constraints from the two epochs assuming that the black hole spin, inner disc inclination, and inner disc iron abundance are invariant. The black hole spin is found to be modest, with a 90 per cent credible range of ${a}^{*}=0.62^{+0.22}_{-0.37}$; and, with a mass MBH in the range log (MBH/M⊙) ∼ 9.2–10.5, this is the most massive black hole candidate for which a well-defined spin constraint has yet been obtained. The modest spin of this black hole supports previous suggestions that the most massive black holes may grow via incoherent or chaotic accretion and/or SMBH-SMBH mergers.
SN 2009ip after a decade: the luminous blue variable progenitor is now gone
Authors: Smith Nathan , Andrews Jennifer E , Filippenko Alexei V , Fox Ori D , Mauerhan Jon C , Van Dyk Schuyler D
Published: June 2022

We present new Hubble Space Telescope (HST) imaging photometry for the site of the Type IIn supernova (SN) 2009ip taken almost a decade after explosion. The optical source has continued to fade steadily since the SN-like event in 2012. In the F606W filter, which was also used to detect its luminous blue variable (LBV) progenitor 13 yr before the SN, the source at the position of SN 2009ip is now 1.2 mag fainter than that quiescent progenitor. It is 6–7 mag fainter than the pre-SN outbursts in 2009–2011. This definitively rules out a prediction that the source would return to its previous state after surviving the 2012 event. Instead, the late-time fading matches expectations for a terminal explosion. The source fades at a similar rate in all visual-wavelength filters without significant colour changes, therefore also ruling out the hypothesis of a luminous dust-obscured survivor or transition to a hotter post-LBV survivor. The late-time continuum with steady colour and strong Hα emission detected in a narrow F657N filter are, however, entirely expected for ongoing shock interaction with circumstellar material in a decade-old core-collapse SN. Interestingly, the ultraviolet flux has stayed nearly constant since 2015, supporting previous conjectures that the F275W light traces main-sequence OB stars in an underlying young star cluster. We expect that the visual-wavelength continuum will eventually level off, tracing this cluster light. Without any additional outbursts, it seems prudent to consider the 2012 event as a terminal SN explosion, and we discuss plausible scenarios.
Inward and outward migration of massive planets: moving towards a stalling radius
Authors: Scardoni Chiara E , Clarke Cathie J , Rosotti Giovanni P , Booth Richard A , Alexander Richard D , Ragusa Enrico
Published: June 2022

Recent studies on the planet-dominated regime of Type II migration showed that, contrary to the conventional wisdom, massive planets can migrate outwards. Using ‘fixed-planet’ simulations, these studies found a correlation between the sign of the torques acting on the planet and the parameter K′ (which describes the depth of the gap carved by the planet in the disc). We perform ‘live-planet’ simulations exploring a range of K′ and disc mass values to test and extend these results. The excitation of planet eccentricity in live-planet simulations breaks the direct dependence of migration rate (rate of change of semimajor axis) on the torques imposed, an effect that ‘fixed-planet’ simulations cannot treat. By disentangling the contribution to the torque due to the semimajor axis evolution from that due to the eccentricity evolution, we recover the relation between the magnitude and sign of migration and K′ and argue that this relation may be better expressed in terms of the related gap depth parameter K. We present a toy model in which the sign of planetary migration changes at a limiting value of K, through which we explore planets’ migration in viscously evolving discs. The existence of the torque reversal shapes the planetary system’s architecture by accumulating planets either at the stalling radius or in a band around it (defined by the interplay between the planet migration and the disc evolution). In either case, planets pile up in the area 1–10 au, disfavouring hot Jupiter formation through Type II migration in the planet-dominated regime.
Morphological decomposition of TNG50 galaxies: methodology and catalogue
Authors: Zana Tommaso , Lupi Alessandro , Bonetti Matteo , Dotti Massimo , Rosas-Guevara Yetli , Izquierdo-Villalba David , Bonoli Silvia , Hernquist Lars , Nelson Dylan
Published: June 2022

We present mordor (MORphological DecOmposeR), a new algorithm for structural decomposition of simulated galaxies based on stellar kinematics. The code measures the properties of up to five structural components (a thin/cold and a thick/warm disc, a classical and a secular bulge, and a spherical stellar halo), and determines the properties of a stellar bar (if present). A comparison with other algorithms presented in the literature yields overall good agreement, with mordor displaying a higher flexibility in correctly decomposing systems and identifying bars in crowded environments (e.g. with ongoing fly-bys, often observable in cosmological simulations). We use mordor to analyse galaxies in the TNG50 simulation and find the following: (i) the thick disc component undergoes the strongest evolution in the binding energy-circularity plane, as expected when disc galaxies decrease their turbulent-rotational support with cosmic time; (ii) smaller galaxies (with stellar mass, $10^{9} \lesssim M_{*}/~\rm M_{\odot }\le 5 \times 10^{9}$) undergo a major growth in their disc components after z ∼ 1, whereas (iii) the most massive galaxies ($5 \times 10^{10} \lt M_{*}/~\rm M_{\odot }\le 5\times 10^{11}$) evolve towards more spheroidal dominated objects down to z = 0 due to frequent gravitational interactions with satellites; (iv) the fraction of barred galaxies grows rapidly at high redshift and stabilizes below z ∼ 2, except for the most massive galaxies that show a decrease in the bar occupation fraction at low redshift; (v) galaxies with $M_{*} \sim 10^{11}~~\rm M_{\odot }$ exhibit the highest relative occurrence of bars at z = 0, in agreement with observational studies. We publicly release mordor and the morphological catalogue of TNG50 galaxies.
Orbital solution and dynamical masses for the nearby binary system GJ 67 AB
Authors: Torres Guillermo
Published: June 2022

We report spectroscopic observations of the nearby, 19.5-yr binary system GJ 67AB spanning more than 35 yr. We carry out a global orbital solution combining our radial-velocity measurements with others from the literature going back more than a century, and with all other available astrometric observations. The latter include measurements of the relative position as well as the Hipparcos intermediate data and photographic observations tracing the motion of the photocentre. We derive masses for the primary and the M-dwarf secondary of 0.95 ± 0.11 and 0.254 ± 0.019 M⊙, respectively, as well as a more accurate trigonometric parallax of 79.08 ± 0.63 mas, which accounts for the orbital motion. We provide evidence suggesting that the much smaller parallax from Gaia DR3 is biased. The precision in the masses remains limited mainly by the still few measurements of the relative position.