bluuebunny/crossref_metadata_2025 huggingface dataset:
Investigating the Capsizing Incident of the RoPax OCD Vessel Utilizing the RAO Approach in Wave Conditions
Authors: Hasanudin  , Zubaydi Achmad , Aryawan Wasis Dwi
Published: July 2023

RoPax is the most famous ship in the world that simultaneously carries multipurpose such as passengers, cargo, and vehicles in bulk. Cargo ships experience the most accidents, but RoPax ships contribute the most casualties worldwide. RoPax OCD is practical and economical for the short-medium route but vulnerable in intact dynamic stability that causes capsize. The paper analyses the data of RoPax Opened Car Deck (OCD) accidents in range time (2003-2021) in Indonesia water that is reviewed by the Response Amplitude Operator (RAO). Internal ship data is obtained from Indonesia’s National Transportation Safety Committee (NTSC), and external data on wave characteristics are obtained from Global Ocean Waves Reanalysis Waves of Copernicus Marine Service. From RAO analysis of eight capsizing cases of RoPax OCD show that 62.5% occur in sub-critical (effect of low stability moment), 25% occur in supercritical (a result of small weight inertia moment), and 12.5% occur in critical (a consequence of small damping moment). The conclusion is that stability problems are the leading cause of the capsizing of RoPax, so existing ships must improve their stability or be diverted to operation areas with suitable wave characteristics.
Driving Blue Economy for Sustainable Development: A case of stakeholder collaboration platform development
Authors: Siswanto N , Rosdaniah S
Published: July 2023

Blue economy (BE) has become one of global actual issues with a multifaceted concept to generate new growth sources from ocean while ensuring environmental sustainability. Indonesia has initiated BE programs since 2012 in Bali and West Nusa Tenggara, featuring an integrated upstream and downstream marine development. However, the targeted outcome of this effort has not yet achieved, due to a number of challenges, including coordination difficulties among stakeholders. An innovation to promote multi-stakeholder collaboration is needed to capture the benefit from the ocean economy. This paper enriches the literature on the BE coordination model by introducing a pilot project of innovative stakeholder engagement platform called BluEconNet. This platform is a digital medium for increasing the involvement of multiple stakeholders to build a participative BE. The platform is designed based on the result of an exploratory approach through literatures review, Focus Group Discussion with representative of stakeholders, combined with semi-structured interviews with representative from institutions. The involvement of stakeholders in the platform is expected to encourage multiple connections and support innovative solutions to provide policymakers with comprehensive information on the ocean economy in order to accelerate the BE development in Indonesia.
Fire Impact Modelling on Human Due to Leakage of Storage Tank at LNG Terminal Using Fire Dynamics Simulator
Authors: Safi’i M H , Husna I Z , Puspitasari N W D , Fahmi F A , Dwianggada R Y , Handani D W
Published: July 2023

The increasing demand for Liquified Natural Gas (LNG) is directly proportional to the risk of LNG Facilities. One of the risks is fire due to leakage of the LNG storage tank at the LNG terminal. This study aims to predict the impact of jet fire on humans due to leaks of LNG storage tanks using Fire Dynamic Simulator and predict the probability of injury or death due to the accident. This simulation uses LNG storage tank capacity as variations including primary data obtained from field surveys. The first results are Hazard and Operability (HAZOP) analysis which found that the cause of the leak was caused by 3 aspects: overpressure, temperature, and corrosion. In addition, the simulation results show 21 deaths due to thermal radiation that occurred in the 20000 m3 storage tank, with a radius of 250 m from the LNG storage tank and a radiation dose of 9,787,223 W4/3sm−8/ 3. Finally, it is recommended that the LNG storage tank be 1200 m3. have a minimum radius of 80 m from the office or housing while the LNG storage tanks of 7500 m3 and 20000 m3 must be 185 m and 250 m apart from the residence.
A Review of Technology Development and Numerical Model Equation for Ocean Current Energy
Authors: Yahya N Y , Silvianita  , Satrio D
Published: July 2023

Scope for of research publications on ocean current energy has increased, resulting in high innovation from ocean energy technology and available models for numerical equations in article publications. Reviews for mapping studies on the development of technology and numerical equations are still rarely carried out. This review refers to articles that use equipment used at sea and are based only on ocean currents for research. From a variety of results of the investigation, it can be expected to be used as material for further studies to find research materials that can be discussed collectively or need to be handled further. The objective of present review study is scanning condition of technology used for analysis and find out the types of numerical equations that are often used in papers in recent years. The result is that various areas of innovation have been investigated in current energy conversion technologies that increase performance and durability and reduce the impact on the environment and have summarised alternative numerical analysis commonly used for current energy conversion technologies.
Ballast Water Treatment with Heat Exchanger Modeling Simulation
Authors: Iswantoro A , Semin  , Pitana T , Zaman M B , Ahsan F I
Published: July 2023

Pollution of the marine environment has become a global issue, including marine pollution from ballast water. The impact is it can damage ecosystems and even affect humans. Therefore, pollution from ballast water is something that must be prevented by ballast water treatment. In this research, the author carried out a modeling simulation on a heat exchanger with a mechanical-type ballast water treatment method by utilizing the heat generated by the ship’s engine. Heat is used to kill microorganisms. So that the ballast water becomes cleaner than without treatment. In this research, the calculation of the need for heat exchangers on certain types of ships with certain sizes is carried out. In this calculation, the ship used is a container type with 3 categories based on cargo capacity and ballast tank capacity. Then the heat from the exhaust gases is used to heat the ballast water of the ship. The simulation results show that the maximum ballast water temperature of each ship category is in the range of 68-75 C. With this temperature, it is sufficient to kill and reduce microorganisms in the ballast water.
Optimization design of remotely operated vehicle (ROV) for Madura Strait Area
Authors: Afifudin I N , Nasirudin A , Aryawan W D , Kurniawati H A , Hasanudin  , Utama D , Putra E I
Published: July 2023

Nowadays, the development of unmanned vehicles is significantly increased. Since the remotely operated vehicle (ROV) has more advantages than Diver. Then, ROV has an important role in underwater inspection and research in various sectors, such as offshore infrastructure development. ROV will give some critical information to the operator about an underwater inspection like bathymetry, pipeline inspection, and the other crucial subsea structure that the divers can’t reach. The optimization design has been carried out to determine ROV operational requirements in Madura Strait by Total-Based Method. ROV will be divided into 3 leading function groups, they are Features, Survive and Operate. Every group will be divided into Function Breakdown Structure (FBS). FBS will be divided again into Work Breakdown Structure (WBS). The optimum design will be determined by linking every breakdown function. The results are the ROV has 2MP 1080P resolution for camera, 2000 lumens for lighting, 50 m detection area for sonar and echosounder, 100 N grip force for Gripper, equipped with stainless steel frame, 2 hours long for operational duration, 5kg.f for thruster, operated with cable 300 m long and equipped with 6-unit thruster.
Study of Wave Parameters in the West side of Java Sea using Wave Spectral Analysis and Zero Up-Crossing Methods
Authors: Panalaran S. , Suntoyo
Published: July 2023

Waves in the sea have a random shape, where the height, length, and direction of the waves change during the observation time. Due to the unpredictable nature of the waves with certain patterns, a statistical and probability approach is needed in analyzing waves. Before carrying out statistical and probability analysis, it is necessary to extract the wave parameters from the random wave data. There are two methods commonly used to extract wave parameters: the first is the individual wave analysis method, using a zero up/down-crossing technique. The second method is the wave spectral analysis method. In this study, both methods will be applied to observation data from the Pabelokan station [1] in the West Java Sea for a six-day. From this study, it was found that the significant wave height parameter generated by the spectral analysis technique and the zero up-crossing technique showed a positive correlation, which the correlation coefficient is 0.9891. In the study of the wave period investigation, both of method have a positive correlation, but the value of the wave period is very likely to be different. The correlation coefficient values for the average wave period are 0.5848 for Tm01
and 0.5757 for Tm02
.
Comparative Analysis of Welding Mechanical Properties FCAW Welding Joint of A36 and A53
Authors: Dhanistha W L , Pratikno H , Maharani S D P , Suntoyo  , Silvianita  , Satrio D
Published: July 2023

A36 and A53 steels are low carbon steel with relatively similar carbon percentage, respectively 0,25-0,30% and 0,25-0,29%. Both steels are often used within the marine industry. The objective of this research is to figure out the effect of the variation of the groove angle and the heat input to the process of welding two different steel plates towards a metallography, tensile, and bending test with E71T electrode, as well as figuring out the groove angle and heat input to weld 18 mm thick steel plates. The variation of the groove angle used are 55°, 60°, and 70° with heat input variation of 140 and 180 A. Results of this experimental study shows that specimen with groove angle 70° and heat input 180 A with the largest sum of HAZ length, which is 8,4 mm, as well as the largest perlite phase, which are respectively, 67% within A36 base metal, 65% on A36 HAZ, 62% on weld metal,63% on A53 HAZ, and 66% on A53 base metal. The largest open defect value in bending tests is 1.87 mm owned by specimens with groove angle of 55° and heat input of 140 A.
Bed shear stress and sediment transport equations for predicting morphological and shoreline changes: a review
Authors: Hidayati N , Suntoyo  , Pratikto W A
Published: July 2023

Coastal sediments can be transported as bedload and suspended-load transport by waves and currents. The waves stir up the sediments, then currents transport sediments. Waves on the bottom can generate bed-shear stress. Meanwhile, the combination of bedload and suspended-load transport is known as total sediment transport. Prediction of total sediment transport has become important related to coastal morphological change and also shoreline change. Most of the sediment transport equations and approaches are developed from the physical principles. There are so many researchers proposed some formulas and methods with some considerations and difficulties. Due to the complexity of coastal conditions, the existing sediment transport rate prediction formulas are still not finished yet. Several well-known equations of bed-shear stress, bedload-suspended transport, and cross shore-longshore sediment transport; are discussed and reviewed in the present study. Thus, an overview of approaches and formulations that are reliable and nearly accurate for calculating the total sediment transport rate based on the characteristics of each coastal waters will be obtained. Accurate estimation of sediment transport rates will provide good results for predicting and monitoring changes in coastal morphology and shoreline changes. Moreover, coastal monitoring can be used for actions related to coastal protection system and coastal management.
Sedimentation of particles with various shapes and orientations in a closed channel using smoothed particle hydrodynamics
Authors: Huang Lizhong , Shao Chun , Wang Ruijin , Du Jiayou , Zhu Zefei
Published: July 2023

The sedimentation of particles with various shapes and orientations in a closed channel using smoothed particle hydrodynamics is investigated in this paper. The continuity and momentum equations of both fluid and solid are discretized using kernel approximation in the Lagrangian frame. The sedimentation behavior of different general shapes, including circle, pentagon, square, ellipse, rectangle, and triangle, at various initial orientations in the suspending fluid is simulated. The stable equilibrium orientation (SEO) of these shapes is examined, excluding the circle which serves as a validation case. Specifically, the major axis of the ellipse and rectangle tends to align horizontally, whereas the orientations of the pentagon and square seem to be random due to the lack of a major axis and the finite channel height. The settling behavior of the three types of triangles is also discussed, and the von Mises stress of these shapes during their settling is presented. This study offers valuable insights into fluid-particle interactions, specifically regarding the SEO and internal stress of settling particles with varying shapes and orientations.
Alternative dental impression fillers made of nanorod glutinous rice flour particles through precipitation
Authors: Takarini Veni , Asri Lia A T W , Djustiana Nina , Hadi Bambang Kismono
Published: July 2023

In this work, nanorod particles were synthesized from a locally available source, glutinous rice flour, using sodium hydroxide (NaOH) through a simple precipitation process. The synthesized nanofillers were then presented as an alternative organic filler for dental impression application to support the making of a diagnostic and working model. Dynamic Light Scattering, Scanning Electron Microscope, Fourier Transform Infrared Spectroscopy, x-ray Diffraction, Energy Dispersive Spectroscopy, Thermogravimetric Analysis, and Differential Scanning Colorimeter were used to characterize the fillers. The particle size measurement, morphology interaction, and composition of glutinous rice flour nanorod particles were also investigated. The cell viability using 3T3L1 cells was assessed to determine the safety of nanorod particles using the MTT assay and trypan blue solution. All treated samples exhibit a change in particle morphology from polyhedral to rod. Additionally, a decrease in crystallinity, dehydration, and gelatinization temperature was observed. The functional group interacting with sodium hydroxide also changes slightly after size reduction. The samples treated with 3000 centrifugation speed without surfactant addition showed changes from the control sample’s 3931.71 nm to the smallest average width particle size of 73.26 nm with an average length of 865.15 nm. All of the treated samples with NaOH and NaOH-surfactant additions met the non-cytotoxicity acceptance criteria in the range of 73.54%–99.58%, according to the cell viability results. The incorporation of 15 wt% of the synthesized nanorod fillers resulted in a 20 μm continuous line as the impression materials specimen, yielding a satisfactory detail reproduction test result. In conclusion, nanorod particles with biocompatible properties have been successfully manufactured and can potentially be used in the future as an alternative dental impression filler materials.
On a quaternary nonlocal isoperimetric problem
Authors: Alama Stanley , Bronsard Lia , Lu Xinyang , Wang Chong
Published: July 2023

We study a two-dimensional quaternary inhibitory system. This free energy functional combines an interface energy favoring micro-domain growth with a Coulomb-type long range interaction energy which prevents micro-domains from unlimited spreading. Here we consider a limit in which three species are vanishingly small, but interactions are correspondingly large to maintain a nontrivial limit. In this limit two energy levels are distinguished: the highest order limit encodes information on the geometry of local structures as a three-component isoperimetric problem, while the second level describes the spatial distribution of components in global minimizers. Geometrical descriptions of limit configurations are derived.
The demarcation problem
Authors: Gordin Michael D.
Published: July 2023

The “demarcation problem” is the philosophical challenge to develop a coherent distinction between science and pseudoscience. The problem received its name and its most famous solution from the Austrian-British philosopher, Karl Popper. Popper’s proposal, “falsifiability,” stated that if a doctrine made knowledge claims that could never possibly be proven false, then the theory was no longer scientific but pseudoscientific. This account is especially popular among scientists, even though in terms of logic and empirical adequacy Popper’s account fails. After describing Popper’s theory and its difficulties, the chapter also gives an account of how it became so widely known as a consequence of debates over creationism. In conclusion, some philosophical alternatives to Popper are discussed.
Genes before 1944
Authors: Slack Jonathan
Published: July 2023

‘Genes before 1944’ outlines the development in our understanding of genes from Gregor Mendel’s work on hereditary factors in 1866, to Oswald Avery’s paper on the chemical composition of DNA and the identity of a ‘transforming principle’ with a gene. Previously there had been some understanding of ‘blood lines’ among animal breeders but this had been uninformed by knowledge of the principles of reproduction. Two completely separate lines of work led to our modern view, and they came together in the mid-20th century to create the new science of molecular biology. One was the study of heredity by biological experimentation and the other was the study of the chemistry of DNA.
BERTwalk for integrating gene networks to predict gene- to pathway-level properties
Authors: Nasser Rami , Sharan Roded
Published: July 2023

Motivation

Graph representation learning is a fundamental problem in the field of data science with applications to integrative analysis of biological networks. Previous work in this domain was mostly limited to shallow representation techniques. A recent deep representation technique, BIONIC, has achieved state-of-the-art results in a variety of tasks but used arbitrarily defined components.

Results

Here, we present BERTwalk, an unsupervised learning scheme that combines the BERT masked language model with a network propagation regularization for graph representation learning. The transformation from networks to texts allows our method to naturally integrate different networks and provide features that inform not only nodes or edges but also pathway-level properties. We show that our BERTwalk model outperforms BIONIC, as well as four other recent methods, on two comprehensive benchmarks in yeast and human. We further show that our model can be utilized to infer functional pathways and their effects.

Availability and implementation

Code and data are available at https://github.com/raminass/BERTwalk.

Contact

roded@tauex.tau.ac.il
PyWGCNA: a Python package for weighted gene co-expression network analysis
Authors: Rezaie Narges , Reese Farilie , Mortazavi Ali
Published: July 2023

Motivation

Weighted gene co-expression network analysis (WGCNA) is frequently used to identify modules of genes that are co-expressed across many RNA-seq samples. However, the current R implementation is slow, is not designed to compare modules between multiple WGCNA networks, and its results can be hard to interpret as well as to visualize. We introduce the PyWGCNA Python package, which is designed to identify co-expression modules from large RNA-seq datasets. PyWGCNA has a faster implementation than the R version of WGCNA and several additional downstream analysis modules for functional enrichment analysis using GO, KEGG, and REACTOME, inter-module analysis of protein–protein interactions, as well as comparison of multiple co-expression modules to each other and/or external lists of genes such as marker genes from single cell.

Results

We apply PyWGCNA to two distinct datasets of brain bulk RNA-seq from MODEL-AD to identify modules associated with the genotypes. We compare the resulting modules to each other to find shared co-expression signatures in the form of modules with significant overlap across the datasets.

Availability and implementation

The PyWGCNA library for Python 3 is available on PyPi at pypi.org/project/PyWGCNA and on GitHub at github.com/mortazavilab/PyWGCNA. The data underlying this article are available in GitHub at github.com/mortazavilab/PyWGCNA/tutorials/5xFAD_paper.
RNAenrich: a web server for non-coding RNA enrichment
Authors: Zhang Song , Amahong Kuerbannisha , Zhang Yintao , Hu Xiaoping , Huang Shijie , Lu Mingkun , Zeng Zhenyu , Li Zhaorong , Zhang Bing , Qiu Yunqing , Dai Haibin , Gao Jianqing , Zhu Feng
Published: July 2023

Motivation

With the rapid advances of RNA sequencing and microarray technologies in non-coding RNA (ncRNA) research, functional tools that perform enrichment analysis for ncRNAs are needed. On the one hand, because of the rapidly growing interest in circRNAs, snoRNAs, and piRNAs, it is essential to develop tools for enrichment analysis for these newly emerged ncRNAs. On the other hand, due to the key role of ncRNAs’ interacting target in the determination of their function, the interactions between ncRNA and its corresponding target should be fully considered in functional enrichment. Based on the ncRNA–mRNA/protein-function strategy, some tools have been developed to functionally analyze a single type of ncRNA (the majority focuses on miRNA); in addition, some tools adopt predicted target data and lead to only low-confidence results.

Results

Herein, an online tool named RNAenrich was developed to enable the comprehensive and accurate enrichment analysis of ncRNAs. It is unique in (i) realizing the enrichment analysis for various RNA types in humans and mice, such as miRNA, lncRNA, circRNA, snoRNA, piRNA, and mRNA; (ii) extending the analysis by introducing millions of experimentally validated data of RNA–target interactions as a built-in database; and (iii) providing a comprehensive interacting network among various ncRNAs and targets to facilitate the mechanistic study of ncRNA function. Importantly, RNAenrich led to a more comprehensive and accurate enrichment analysis in a COVID-19-related miRNA case, which was largely attributed to its coverage of comprehensive ncRNA–target interactions.

Availability and implementation

RNAenrich is now freely accessible at https://idrblab.org/rnaenr/.
Blocking an epitope of misfolded SOD1 ameliorates disease phenotype in a model of amyotrophic lateral sclerosis
Authors: Bakavayev Shamchal , Stavsky Alexandra , Argueti-Ostrovsky Shirel , Yehezkel Galit , Fridmann-Sirkis Yael , Barak Zeev , Gitler Daniel , Israelson Adrian , Engel Stanislav
Published: July 2023

The current strategies to mitigate the toxicity of misfolded superoxide dismutase 1 (SOD1) in familial amyotrophic lateral sclerosis via blocking SOD1 expression in the CNS are indiscriminative for misfolded and intact proteins, and as such, entail a risk of depriving CNS cells of their essential antioxidant potential. As an alternative approach to neutralize misfolded and spare unaffected SOD1 species, we developed scFv-SE21 antibody that blocks the β6/β7 loop epitope exposed exclusively in misfolded SOD1.

The β6/β7 loop epitope has previously been proposed to initiate amyloid-like aggregation of misfolded SOD1 and mediate its prion-like activity. The adeno-associated virus-mediated expression of scFv-SE21 in the CNS of hSOD1G37R mice rescued spinal motor neurons, reduced the accumulation of misfolded SOD1, decreased gliosis and thus delayed disease onset and extended survival by 90 days.

The results provide evidence for the role of the exposed β6/β7 loop epitope in the mechanism of neurotoxic gain-of-function of misfolded SOD1 and open avenues for the development of mechanism-based anti-SOD1 therapeutics, whose selective targeting of misfolded SOD1 species may entail a reduced risk of collateral oxidative damage to the CNS.
Integrin beta-like 1 mediates fibroblast–cardiomyocyte crosstalk to promote cardiac fibrosis and hypertrophy
Authors: Chen XiaoQiang , Li XinTao , Wu XiaoYu , Ding Yu , Li Ya , Zhou GenQing , Wei Yong , Chen SongWen , Lu XiaoFeng , Xu Juan , Liu ShaoWen , Li Jun , Cai LiDong
Published: July 2023

Aims

Crosstalk between fibroblasts and cardiomyocytes (CMs) plays a critical role in cardiac remodelling during heart failure (HF); however, the underlying molecular mechanisms remain obscure. Recently, a secretory protein, Integrin beta-like 1 (ITGBL1) was revealed to have detrimental effects on several diseases, such as tumours, pulmonary fibrosis, and hepatic fibrosis; whereas the effect of ITGBL1 on HF is unclear. The purpose of this study was to evaluate its contribution to volume overload-induced remodelling.

Methods and results

In this study, we identified ITGBL1 was highly expressed in varied heart diseases and validated in our TAC mice model, especially in fibroblasts. To investigate the role of ITGBL1 in in vitro cell experiments, neonatal rat fibroblasts (NRCFs) and cardiomyocytes (NRCMs) were performed for further study. We found that in comparison to NRCMs, NRCFs expressed high levels of ITGBL1. Meanwhile, ITGBL1 was upregulated in NRCFs, but not in NRCMs following angiotensin-II (AngII) or phenylephrine stimulation. Furthermore, ITGBL1 overexpression promoted NRCFs activation, whereas knockdown of ITGBL1 alleviated NRCFs activation under AngII treatment. Moreover, NRCFs-secreted ITGBL1 could induce NRCMs hypertrophy. Mechanically, ITGBL1-NME/NM23 nucleoside diphosphate kinase 1 (NME1)-TGF-β-Smad2/3 and Wnt signalling pathways were identified to mediate NRCFs activation and NRCMs hypertrophy, respectively. Finally, the knockdown of ITGBL1 in mice subjected to transverse aortic constriction (TAC) surgery recapitulated the in vitro findings, demonstrating blunted cardiac fibrosis, hypertrophy, and improved cardiac function.

Conclusions

ITGBL1 is an important functional mediator between fibroblast–cardiomyocyte crosstalk and could be an effective target for cardiac remodelling in HF patients.
Deaf Identity, Social Relationships, and Social Support: Toward a Microsociological Perspective
Authors: Chapman Madeleine , Dammeyer Jesper , Jepsen Kim Sune Karrasch , Liebst Lasse Suonperä
Published: July 2023

This study is the first to analyze data from a national survey to investigate the significance for deaf identity of the different forms of social and technological support that deaf people rely upon. Data were derived from a survey among 839 deaf people and were analyzed with regard to social identification as deaf, hearing, bicultural, and marginal. Findings showed connections between technology and identity, including the use of a range of technology to support being culturally deaf. Findings also showed that the deaf and hearing groups had strong homophilous social networks, while the bicultural group tended toward more mixed but equally strong social connectivity. The marginal group had a much thinner social connectivity and relied more upon institutional social support, findings that are in line with previous research revealing a sub-group struggling with social participation and well-being. Theoretically, the paper builds bridges between the fields of social identity and microsociology and shows how a microsociological perspective brings attention to the significance of reiterated social relations and practice for constructing social identity.
The world Delhi wants: official Indian conceptions of international order, c. 1998–2023
Authors: Mishra Atul
Published: July 2023

Examining India's official thinking on international order over the past quarter-century, this article maps the shift in the country's preference from liberal internationalism to the rules-based international order (RIO). It argues that despite Delhi's current narrative of a ‘New India’, the country's order conception shows continuity in being essentially reformist and mostly consistent with the pillars of the 1945 order. While its marked unease with liberalism is a consequence of the changes afoot in India's domestic politics, this development is consistent with, and contributes to, the decline of liberalism as a global force. The current Indian preference for economic protectionism also reflects the larger trend of economic deglobalization. The description of India as a resurgent civilizational state rather than a liberal democracy, while discursively arresting, does not indicate a divergence with the West on the grand strategic question of order-building. Upon reconstructing the Indian iteration of the RIO, the article finds it to be geographical—focused on Asia and the Indo-Pacific—rather than universal. Finally, it posits that India's persisting problem of inadequate power and its risk-averse responses to great power revisionism are likely to undermine its efforts to effectively partner with democracies to shape the emergent RIO.
Singapore's conception of the liberal international order as a small state
Authors: Loh Dylan M H
Published: July 2023

The liberal international order (LIO) is undergoing significant challenges, and this has given rise to debates about its purported decline. In this context, most studies of the LIO focus on major powers with little attention paid to small states’ conceptualizations of the LIO despite its ubiquity in international life. Focusing on the Singaporean case as a small state, it asks the question: how does Singapore conceptualize the LIO and what are the effects of this conceptualization? Through a mixed-method thematic analysis of 192 parliamentary replies, media interviews and United Nations speeches by Singaporean officials between 2000 to 2022, I find Singapore accepting and defending the existing international order in two main ways: demonstrating respect for international law and the UN Charter, and supporting economic liberalism. Meanwhile, Singapore is contesting the universality of liberal democracy as it sees such discourse as a rebuke to its single-party dominant governance model. This perception of the LIO, in turn, informs Singapore's order-maintaining, order-modifying and order-contesting practices: it seeks to not only protect, but also to modify the LIO—through institutional and legal initiatives—to make it more equitable and open, giving us a glimpse into an instance of a small state's agency in relation to the LIO.
Long-Term Efficacy and Safety of Paliperidone 6-Month Formulation: An Open-Label 2-Year Extension of a 1-Year Double-Blind Study in Adult Participants With Schizophrenia
Authors: Najarian Dean , Turkoz Ibrahim , Knight R Karl , Galderisi Silvana , Lamaison Hector F , Zalitacz Piotr , Aravind Suresh , Richarz Ute
Published: July 2023

Background

Paliperidone palmitate 6-month (PP6M) demonstrated noninferiority to paliperidone palmitate 3-month in preventing relapse in patients with schizophrenia in a phase 3 double-blind (DB) study (NCT03345342). Here, we report long-term efficacy and safety results from a 2-year single-arm, open-label extension (OLE; NCT04072575) of this DB study.

Methods

Participants who completed the DB study without relapse were enrolled and followed-up every 3 months up to 2 years. Participants received 4 PP6M gluteal injections (700/1000 mg eq.) at baseline, 6-month, 12-month, and 18-month visits. Efficacy endpoints included assessment of relapse, Positive and Negative Syndrome Scale total score, Personal and Social Performance score, and Clinical Global Impression-Severity scale change from baseline. Safety was assessed by treatment-emergent adverse events (TEAEs), physical examinations, and laboratory tests.

Results

Of 178 participants enrolled, 154 (86.5%) completed the OLE (mean age: 40.4 years, men: 70.8%; mean duration of PP6M exposure during OLE: 682.1 days). Overall, 7/178 (3.9%) participants relapsed between 20 and 703 days after enrolment. Mean (SD) changes from baseline to endpoint were as follows: Positive and Negative Syndrome Scale total score, 0.7 (8.22); Clinical Global Impression-Severity, 0.0 (0.51); and Personal and Social Performance Scale, 0.5 (7.47). Overall, 111/178 participants (62.4%) reported ≥1 TEAE; most common (>5%) TEAEs were headache (13.5%) and increased blood prolactin/hyperprolactinemia (18.0%); 8/178 (4.5%) participants experienced serious TEAEs, and 6/178 (3.4%) participants withdrew due to TEAEs. No deaths were reported.

Conclusions

The relapse rate observed with PP6M during the 2-year OLE was low (3.9%). Clinical and functional improvements demonstrated in the DB study were maintained during OLE, and no new safety concerns were identified.

Trial registration

ClinicalTrials.gov Identifier: NCT04072575; EudraCT number: 2018-004532-30.
Superficial non-ampullary duodenal epithelial tumors now: endoscopic diagnosis and therapy
Authors: Hirose Takashi , Kato Motohiko , Hatta Waku , Abe Seiichiro , Takizawa Kohei , Yano Tomonori
Published: July 2023

With the recent increase in the frequency of duodenal tumor detection, significant progress has been made in endoscopic diagnosis and treatment. Although the first guidelines were issued in Japan, patient treatment varies widely among institutions. There is a need for improving the quality of endoscopic diagnosis and more curative and safer treatments. Biopsy is the standard diagnostic method; however, the diagnostic accuracy of endoscopic biopsy is not so high. Therefore, the differentiation of superficial non-ampullary duodenal epithelial tumors from non-neoplastic lesions is being developed. The incidence of lymph node and distant metastases of duodenal epithelial tumors is extremely rare in intramucosal carcinomas, and they are considered good candidates for endoscopic treatment if the technical difficulties can be resolved. Adverse events associated with endoscopic treatment are greatly reduced at advanced facilities through novel resection and closure methods, and further improvements are expected in the future. Clarifying the risk of metastatic recurrence may lead to the development of more appropriate treatments and curative resection criteria.
Safety and efficacy of venetoclax for acute myeloid leukaemia in real-world clinical practice
Authors: Fukumoto Ami , Narita Kentaro , Ikeda Daisuke , Uesugi Yuka , Tabata Rikako , Miura Daisuke , Takeuchi Masami , Matsue Kosei
Published: July 2023

Venetoclax combined with low-intensity chemotherapy has led to longer survival and higher remission rates in patients with untreated acute myeloid leukaemia who are ineligible for intensive chemotherapy. We reviewed 41 newly diagnosed and relapse/refractory acute myeloid leukaemia patients who received venetoclax at our institute. Complete remission or complete remission with incomplete recovery was achieved in 73.1% of patients. A total of 95.1% of patients discontinued venetoclax, mainly because of severe cytopenia, disease progression and haematopoietic stem cell transplantation. The median number of courses of venetoclax was 2. In all, 92.6% of the patients experienced grade ≥ 3 neutropenia. The median overall survival was 287 days. Venetoclax dose reduction resulted in better continuity of treatment with fewer complications. In conclusion, venetoclax and low-intensity chemotherapy led to high remission rates, but survival was restrained because of the large number of venetoclax discontinuations. Dose reduction of venetoclax may mitigate cytopenia while maintaining efficacy.
DNA-PK is activated by SIRT2 deacetylation to promote DNA double-strand break repair by non-homologous end joining
Authors: Head PamelaSara E , Kapoor-Vazirani Priya , Nagaraju Ganji P , Zhang Hui , Rath Sandip K , Luong Nho C , Haji-Seyed-Javadi Ramona , Sesay Fatmata , Wang Shi-Ya , Duong Duc M , Daddacha Waaqo , Minten Elizabeth V , Song Boying , Danelia Diana , Liu Xu , Li Shuyi , Ortlund Eric A , Seyfried Nicholas T , Smalley David M , Wang Ya , Deng Xingming , Dynan William S , El-Rayes Bassel , Davis Anthony J , Yu David S
Published: July 2023

DNA-dependent protein kinase (DNA-PK) plays a critical role in non-homologous end joining (NHEJ), the predominant pathway that repairs DNA double-strand breaks (DSB) in response to ionizing radiation (IR) to govern genome integrity. The interaction of the catalytic subunit of DNA-PK (DNA-PKcs) with the Ku70/Ku80 heterodimer on DSBs leads to DNA-PK activation; however, it is not known if upstream signaling events govern this activation. Here, we reveal a regulatory step governing DNA-PK activation by SIRT2 deacetylation, which facilitates DNA-PKcs localization to DSBs and interaction with Ku, thereby promoting DSB repair by NHEJ. SIRT2 deacetylase activity governs cellular resistance to DSB-inducing agents and promotes NHEJ. SIRT2 furthermore interacts with and deacetylates DNA-PKcs in response to IR. SIRT2 deacetylase activity facilitates DNA-PKcs interaction with Ku and localization to DSBs and promotes DNA-PK activation and phosphorylation of downstream NHEJ substrates. Moreover, targeting SIRT2 with AGK2, a SIRT2-specific inhibitor, augments the efficacy of IR in cancer cells and tumors. Our findings define a regulatory step for DNA-PK activation by SIRT2-mediated deacetylation, elucidating a critical upstream signaling event initiating the repair of DSBs by NHEJ. Furthermore, our data suggest that SIRT2 inhibition may be a promising rationale-driven therapeutic strategy for increasing the effectiveness of radiation therapy.
Dimerization of an umbravirus RNA genome activates subgenomic mRNA transcription
Authors: Chkuaseli Tamari , White K Andrew
Published: July 2023

Many eukaryotic RNA viruses transcribe subgenomic (sg) mRNAs during infections to control expression of a subset of viral genes. Such transcriptional events are commonly regulated by local or long-range intragenomic interactions that form higher-order RNA structures within these viral genomes. In contrast, here we report that an umbravirus activates sg mRNA transcription via base pair-mediated dimerization of its plus-strand RNA genome. Compelling in vivo and in vitro evidence demonstrate that this viral genome dimerizes via a kissing-loop interaction involving an RNA stem-loop structure located just upstream from its transcriptional initiation site. Both specific and non-specific features of the palindromic kissing-loop complex were found to contribute to transcriptional activation. Structural and mechanistic aspects of the process in umbraviruses are discussed and compared with genome dimerization events in other RNA viruses. Notably, probable dimer-promoting RNA stem-loop structures were also identified in a diverse group of umbra-like viruses, suggesting broader utilization of this unconventional transcriptional strategy.
Structural underpinnings of mutation rate variations in the human genome
Authors: Liu Zian , Samee Md Abul Hassan
Published: July 2023

Single nucleotide mutation rates have critical implications for human evolution and genetic diseases. Importantly, the rates vary substantially across the genome and the principles underlying such variations remain poorly understood. A recent model explained much of this variation by considering higher-order nucleotide interactions in the 7-mer sequence context around mutated nucleotides. This model's success implicates a connection between DNA shape and mutation rates. DNA shape, i.e. structural properties like helical twist and tilt, is known to capture interactions between nucleotides within a local context. Thus, we hypothesized that changes in DNA shape features at and around mutated positions can explain mutation rate variations in the human genome. Indeed, DNA shape-based models of mutation rates showed similar or improved performance over current nucleotide sequence-based models. These models accurately characterized mutation hotspots in the human genome and revealed the shape features whose interactions underlie mutation rate variations. DNA shape also impacts mutation rates within putative functional regions like transcription factor binding sites where we find a strong association between DNA shape and position-specific mutation rates. This work demonstrates the structural underpinnings of nucleotide mutations in the human genome and lays the groundwork for future models of genetic variations to incorporate DNA shape.
Human TRMT2A methylates tRNA and contributes to translation fidelity
Authors: Witzenberger Monika , Burczyk Sandra , Settele David , Mayer Wieland , Welp Luisa M , Heiss Matthias , Wagner Mirko , Monecke Thomas , Janowski Robert , Carell Thomas , Urlaub Henning , Hauck Stefanie M , Voigt Aaron , Niessing Dierk
Published: July 2023

5-Methyluridine (m5U) is one of the most abundant RNA modifications found in cytosolic tRNA. tRNA methyltransferase 2 homolog A (hTRMT2A) is the dedicated mammalian enzyme for m5U formation at tRNA position 54. However, its RNA binding specificity and functional role in the cell are not well understood. Here we dissected structural and sequence requirements for binding and methylation of its RNA targets. Specificity of tRNA modification by hTRMT2A is achieved by a combination of modest binding preference and presence of a uridine in position 54 of tRNAs. Mutational analysis together with cross-linking experiments identified a large hTRMT2A–tRNA binding surface. Furthermore, complementing hTRMT2A interactome studies revealed that hTRMT2A interacts with proteins involved in RNA biogenesis. Finally, we addressed the question of the importance of hTRMT2A function by showing that its knockdown reduces translation fidelity. These findings extend the role of hTRMT2A beyond tRNA modification towards a role in translation.
Cucumber abscisic acid 8′-hydroxylase Csyf2 regulates yellow flesh by modulating carotenoid biosynthesis
Authors: Wang Xueting , Jin Boyan , Yan Wenjing , Wang Jiaxi , Xu Jun , Cai Congxi , Qi Xiaohua , Xu Qiang , Yang Xiaodong , Xu Xuewen , Chen Xuehao
Published: July 2023

Cucumber (Cucumis sativus L.) flesh is typically colorless or pale green. Flesh with yellow or orange pigment, determined mainly by carotenoid content and composition, is mostly found in semi-wild Xishuangbanna cucumber, which has a very narrow genetic background. Here, we identified a spontaneous cucumber mutant with yellow flesh (yf-343), which accumulated more β-cryptoxanthin and less lutein than regular cultivated European glasshouse-type cucumbers. Genetic analysis revealed that the yellow flesh phenotype was controlled by a single recessive gene. Through fine mapping and gene sequencing, we identified the candidate gene C. sativus yellow flesh 2 (Csyf2), encoding an abscisic acid (ABA) 8′-hydroxylase. Overexpression and RNAi-silencing of Csyf2 in cucumber hairy roots produced lower and higher ABA contents than in non-transgenic controls, respectively. Further, RNA-seq analysis suggested that genes related to ABA signal transduction were differentially expressed in fruit flesh between yf-343 and its wild type, BY, with white flesh. The carotenoid biosynthesis pathway was specifically enriched in fruit flesh at 30 days after pollination when yf-343 fruit flesh turns yellow. Our findings highlight a promising target for gene editing to increase carotenoid content, expanding our genetic resources for pigmented cucumber flesh breeding for improving the nutritional quality of cucumber.
The extracellular matrix of green algae
Authors: Domozych David S , LoRicco Josephine G
Published: July 2023

Green algae display a wide range of extracellular matrix (ECM) components that include various types of cell walls (CW), scales, crystalline glycoprotein coverings, hydrophobic compounds, and complex gels or mucilage. Recently, new information derived from genomic/transcriptomic screening, advanced biochemical analyses, immunocytochemical studies, and ecophysiology has significantly enhanced and refined our understanding of the green algal ECM. In the later diverging charophyte group of green algae, the CW and other ECM components provide insight into the evolution of plants and the ways the ECM modulates during environmental stress. Chlorophytes produce diverse ECM components, many of which have been exploited for various uses in medicine, food, and biofuel production. This review highlights major advances in ECM studies of green algae.
Transcription factors TgbHLH95 and TgbZIP44 cotarget terpene biosynthesis geneTgGPPSinTorreya grandisnuts
Authors: Zhang Zuying , Tao Liu , Gao Lingling , Gao Yadi , Suo Jinwei , Yu Weiyu , Hu Yuanyuan , Wei Chunyan , Farag Mohamed A , Wu Jiasheng , Song Lili
Published: July 2023

Terpenes are volatile compounds responsible for aroma and the postharvest quality of commercially important xiangfei (Torreya grandis) nuts, and there is interest in understanding the regulation of their biosynthesis. Here, a transcriptomics analysis of xiangfei nuts after harvest identified 156 genes associated with the terpenoid metabolic pathway. A geranyl diphosphate (GPP) synthase (TgGPPS) involved in production of the monoterpene precursor GPP was targeted for functional characterization, and its transcript levels positively correlated with terpene levels. Furthermore, transient overexpression of TgGPPS in tobacco (Nicotiana tabacum) leaves or tomato (Solanum lycopersicum) fruit led to monoterpene accumulation. Analysis of differentially expressed transcription factors identified one basic helix-loop-helix protein (TgbHLH95) and one basic leucine zipper protein (TgbZIP44) as potential TgGPPS regulators. TgbHLH95 showed significant transactivation of the TgGPPS promoter, and its transient overexpression in tobacco leaves led to monoterpene accumulation, whereas TgbZIP44 directly bound to an ACGT-containing element in the TgGPPS promoter, as determined by yeast 1-hybrid test and electrophoretic mobility shift assay. Bimolecular fluorescence complementation, firefly luciferase complementation imaging, co-immunoprecipitation, and GST pull-down assays confirmed a direct protein–protein interaction between TgbHLH95 and TgbZIP44 in vivo and in vitro, and in combination these proteins induced the TgGPPS promoter up to 4.7-fold in transactivation assays. These results indicate that a TgbHLH95/TgbZIP44 complex activates the TgGPPS promoter and upregulates terpene biosynthesis in xiangfei nuts after harvest, thereby contributing to its aroma.