bluuebunny/crossref_metadata_2025 huggingface dataset:
Rock mass geomechanical properties to improve rockfall susceptibility assessment: a case study in Valchiavenna (SO)
Authors: Bajni G , Camera C A S , Brenning A , Apuani T
Published: September 2021

The overarching goal of the study is to develop a rockfall susceptibility map for Valchiavenna (SO), located in the Italian Central Alps. The approach was two-fold: the first part of the work consisted of developing geomechanical maps, which are relevant to rock mass instability, whilst the second part was aimed to the implementation of the obtained geomechanical maps as predictors in a statistically based rockfall susceptibility model. The chosen target variables, collected in an available geomechanical field surveys database, were Joint Volumetric Count (Jv), the equivalent hydraulic conductivity (Keq), and weathering index (Wi). The available dataset was updated with several new geomechanical surveys, whose locations were chosen through the application of the Spatial Simulated Annealing algorithm. Based on this updated and homogenised dataset, the target properties were regionalized using different deterministic, geostatistical and regression techniques, comparing performance and error metrics resulting from a leave-one-out cross-validation procedure. Regionalization results of the target variables showed different reliability degrees. To improve the hydrogeological processes understanding on another spatial scale, an infiltration density map was prepared, based on field-mapped elements prone to infiltration-Rockfall susceptibility modelling was performed using Generalized Additive Models (GAM), along with the more commonly used topographic predictors. Model performance is assessed using both non-spatial and spatial k-fold cross-validations to estimate the area under the receiver operating characteristic curve (AUROC). Predictor smoothing functions and deviance explained were analysed in order to assess the influence of the geomechanical predictors on the model. The geological-geomorphological plausibility of the susceptibility map including geomechanical predictors was assessed by a comparison with the only topography-based susceptibility map. Model results showed reliable rockfall discrimination capabilities (mean AUROC>0.7). Rockfall data for model training and testing were extracted from the IFFI (Inventario dei Fenomeni Franosi in Italia) inventory and updated with additional field-mapped rockfalls. A potential inventory bias in the IFFI inventory was observed by comparing performance and predictors behaviour of models built with and without the additional rockfalls.
A new gradient elasticity model for the elastic boreholes
Authors: Efremidis G , Tsagrakis I
Published: September 2021

A new gradient elasticity model is employed to discuss strain gradient effects and its ability in predicting size effects on an elastic rock mass with microstructure, around an axisymmetric borehole under internal pressure and remote isotropic compressive stress. The constitutive equation of the model involves the Laplacian of the strain tensor multiplied by the gradient coefficient. The formulated boundary value problem is solved analytically to derive stress, strain, and displacement distributions and discuss respective gradient effects on the mechanical behavior of the rock mass and the corresponding borehole stability. The paper concludes with the employment of the Rankine failure criterion to investigate size effects on the stress concentration factor at the perimeter of the borehole, and the comparison with another gradient elasticity model which involves the Laplacian of the hydrostatic part of the strain tensor.
Effect of thermo-hydro-mechanical coupling on the evolution of stress in the concrete liner of an underground drift in the Cigéo project
Authors: Alonso M , Vu M N , Vaunat J , Armand G , Gens A , Plua C , De Lesquen C , Ozanam O
Published: September 2021

The French National Radioactive Waste Management Agency (Andra) is in charge of studying the disposal of high-level and intermediate-level long-lived waste (HLW and ILW-LL) in a deep geological repository (Cigéo project) within the host formation is the Callovo-Oxfordian claystone (COx). The heat emitted from waste packages induces a thermo-hydro-mechanical (THM) coupling within the structural elements and the host rock. This study focuses on the behavior of the concrete lining of an ILW-LL cell subjected to THM loading during its construction and operational phases. The mechanical behavior of the host rock is represented by an elasto-visco-plastic model taking into account the anisotropies in stiffness and strength. The coupled THM formulation is based on the Biot theory. Different simulations including full THM coupling and HM coupling with or without creep behavior of COx claystone have been performed to show the effect of the thermal load (generated by the waste packages), of the water seepage and of the creep strain of the host rock on the stress evolution in the concrete liner. The results show the preponderant role of the creep strain of COx claystone on the stress state of the liner during the operational phase, while the effect of the heat loading is moderate and that of the seepage is not significant.
Evaluation on floral visitors of Zingiber spectabile (Zingiberaceae) at Gua Ikan, Kelantan, Peninsular Malaysia
Authors: Arumugam N , Jayaraj V K , Subramaniam S , Appalasamy S
Published: September 2021

Insects are the well-known pollinators of angiosperm plants. However, the discovery of specific insect pollinators of a specific plant is still lacking in many angiosperms. Family Zingiberaceae which is also known as a ginger family, is one of the least explored angiosperms in the aspect of plant-pollinator interaction. Hence, this study was conducted to understand the interaction between Zingiber spectabile and pollinators. The aims of the study are i) to determine the floral blooming period of Z. spectabile; ii) to identify floral visitor of Z. spectabile; iii) to identify the insect pollinators of Z. spectabile. The study was conducted in the limestone forest of Gua Ikan (Dabong, Kelantan) in September 2020. Direct observation method was used to achieve the above-mentioned objectives. Observation was performed from 0700 hours to 2000 hours. A floral visitor was counted as pollinator when the insect touches the sexual organs of the flower. This study reveals that flower of Z. spectabile have a lifespan of less than a day. Flower opening (anthesis) starts at 1000 hours while flower closure time starts at 2000 hours. An inflorescence of Z. spectabile produce one to three flowers per day. Insect order Coleoptera, Diptera, Hemiptera, Hymenoptera and Lepidoptera are the common floral visitors of the Z. spectabile. However, among the floral visitors, order Diptera, Hemiptera and Lepidoptera were found to play the role of pollinator for Z. spectabile. This study reveals the fundamental information about pollinators of Z. spectabile. Further detailed study is recommended to reveal the effects of floral scent in attracting the pollinators as further evaluation of Zingiberaceae-pollinator interaction.
Spatio-temporal analysis of rainfall data in Kuala Krai Kelantan
Authors: Muhammad M , Ibrahim Q A Q , Ghani M S M , Jemali N , Awang N R
Published: September 2021

This paper interpreted spatio-temporally the relationship between event of weather activities and flooding in Kuala Krai Kelantan. During the Kelantan big yellow flood event in December 2014, Kuala Krai was one of the worst affected area with the rarity of the return period approximately 1 in 1000 years. Many say this is due to the unusual occurrence of extreme rainfall. Therefore, this research work on spatio-temporal analysis of the time series rainfall data in Kuala Krai Kelantan, to describe and determine the behaviour and pattern of the data. The data on the monthly amount of rainfall between (2013-2019), were collected from Department Irrigation and Drainage (DID). The main aim of this study is to statistically determine whether it is true the flooding in Kuala Krai Kelantan on 2014 is because of heavy rainfall. The collected rainfall data had been spatially analysed using ArcGIS to compare the distribution of rainfall from year 2013 to 2019. Then, the trend pattern of the data had been determined using Mann Kendall Test and Sen’s slope Test. From those analysis it can be concluded that the huge amount of rainfall intensity is the major factor that contribute the extreme flood event in Kuala Krai Kelantan on December 2014.
Comparison of terrestrial vertebrates between natural and teak plantation forest in Peninsular Malaysia: A case study in Perlis State Park and Mata Ayer Field Center, FRIM
Authors: Mahyudin N A A , Munian K , Shahfiz M A , Fauzi N FM , Ahmad Ruzman N H , Baharudin M S , Zam Beri A Z , AAzhar M , Fauzi M SA
Published: September 2021

Species compositions are influenced by the habitat types and methods used in a study. The objectives of this study are to document species diversity in teak plantation in Mata Ayer Research Station, FRIM and to compare differences in species diversity and composition between plantation and natural forest of Perlis State Park. Different types of traps and methods were used to survey four targeted groups of vertebrates (small mammal, bird, reptile and amphibian), including mist net, harp trap, collapsible trap, and active search. A total of 252 individuals were captured, representing 117 species of 53 families of vertebrates. Alpha diversity analysis shows that natural forest has higher species diversity than a teak plantation. Shannon-Weiner Index show higher result in natural forest (3.768) than teak plantation (3.439) while evenness of species distribution is higher in teak plantation (0.8419) than the natural forest (0.4755). Sorenson dissimilarity index indicates that 90.4% significant difference between sites thus; both sites have different species composition of vertebrates. Taxonomic distinctness however reflects different significant variation responses of both areas. Natural forest shows more species compared to plantation forest as it provides more food resources, suitable home and higher rate of reproduction while teak plantation shows a similar habitable environment with structural and conditions more similar to natural forest. So, both natural forest and plantation should be protected, manage and use suitable planning in order to sustain the biodiversity for future generation.
Optimisation and growth kinetic analysis of Microalgae, Arthrospira platensis in 2-L Photobioreactors
Authors: Hussin A A , To S W , Sani M H , Amin M F M , Kamaroddin M F
Published: September 2021

In recent years, photoautotrophic microalgae are widely recognised due to their diverse yet significant natural values, particularly in healthcare, including pharmaceuticals, cosmetics and feedstock industries. One of the most exploited blue-green microalgae, Arthrospira sp. has been addressed as a potent superfood. However, the microalgal mass-production requires suitable inoculum strain and controlled cultivation conditions for enhanced growth performance. Hence, this study aimed to maximise biomass of Arthrospira platensis chosen strain in a 2 litres indoor photobioreactor under three different parameters which were aeration rate, light intensity and pH of the medium. In the present study, a comparative study of growth performance between helical (S1) and straight form (S2) of A. platensis was conducted and the results revealed that morphological differences did not affect growth performances. Meanwhile, the optimisation based on the parameters studied shows that cultivation of A. platensis with aeration of 0.5 L/min and medium of pH 9.0 yielded the highest biomass production which were 1.500 ± 0.049 g/L. Under different light intensity, A. platensis produced the highest biomass and maximum specific growth rate of 1.142 ± 0.037 g/L and 0.716 ± 0.018 1/day, respectively when cultivated under irradiance of 6000 Lux. In conclusion, compared to before optimisation, biomass and maximum specific growth rate after optimisation was 137% and 24% increased, respectively.
Vertical distribution of heavy metals in core sediments from Kelantan River off Tanah Merah, Kelantan, Malaysia
Authors: Yusoff A H , Azmi M S W , Chang C S , Sulaiman A F , Nor A N M , Tan R , Ahmed M F
Published: September 2021

Core sediments from two sampling points namely TM 2 and TM3 which are located at the Kelantan Rive near to Tanah Merah district had been collected to determine the vertical profile of heavy metals contents. TM 2 and TM3 were located near to gold mining area and agriculture area, respectively. The heavy metals in Tanah Merah were analysed using Atomic Absorption Spectrophotometer (AAS) PinA Acle 900F model. The degree of pollution has been investigated using Geo-accumulation (Igeo) index. For the result, the average value of heavy metals in Tanah Merah are Cu (12.67 ± 5.38 mg/kg), Pb (44.57 ± 8.75 mg/kg), Cr (56.69. ± 10.38 mg/kg), Zn (157.89 ± 88.56 mg/kg), Fe (4.08 ± 0.82 %) and Al (7.84 ± 1.53 %). The vertical profile of Cu and Zn at the bottom layer showed the decreasing trend toward the bottom of sediment suggesting the additional anthropogenic input of both metals to the sediment. In addition, most of the concentration value of Zn at TM2 near to gold mining set were exceed the permissible limit set by WHO. Furthermore, the result from the Igeo index also supported sediments at TM 2 which is located near to mining area are extremely contaminated with Cu and Zn. As conclusion, the authorities should closely monitor the level of pollution at the Kelantan River especially near to mining area.
Estimation of aboveground biomass using allometric relationship between DBH and height for mixed mangrove forest in Setiu Wetland, Terengganu, Malaysia
Authors: Kasawani I , Mohd-Zaki A , Onrizal  , Zulhazman H
Published: September 2021

A study was conducted to determine aboveground biomass in a mixed mangrove forest in Setiu Wetland, Terengganu, Malaysia. A total of 22 plots were established, diameter breast height (DBH) and height of each of the trees were measured and recorded. A total of three species from Rhizophoraceae and eight species from the non-Rhizophoraceae family were recorded. The highest no. of species for Rhizophoraceae is Bruguiera cylindrica with 189 individuals, meanwhile for non-Rhizophoraceae is Heritiera littoralis with 36 individuals. Linear regression between DBH to height had been done for stem allometry analysis for each species with Avicennia lanata shows good fit (r2 = 0.906). The total aboveground biomass was 5 202.23 kg ha−1. A. lanata recorded the highest (983.78 kg ha−1) total aboveground biomass because of various ranges of DBH and height. Linear regression also had been done between aboveground biomass to DBH and height. Rhizophora apiculata (Rhizophoraceae) and Excoecaria agallocha (non-Rhizophoraceae) show the highest value of regression between aboveground biomass to DBH which are r2 = 0.925 and r2 = 0.948 while B. gymnorrhiza (Rhizophoraceae) and Xylocarpus granatum (non-Rhizophoraceae) show the highest value of regression between aboveground biomass to height with r2 = 0.806 and r2 = 0.839. Overall, non-Rhizophoraceae have higher aboveground biomass as compared to Rhizophoraceae.
Key Biodiversity Areas (KBA): An Important Approach in Mainstreaming Biodiversity Conservation in Malaysia
Authors: Ahmad Ruzman N H , Shahfiz M A , Munian K , Fauzi N F M , Azahar M A , Zam Beri A Z , Appanan M , Baharudin M S , Mahyudin N A A
Published: September 2021

Malaysia has adopted two ways of conserving its biodiversity; species-based and landscape-based approaches. However, there are limitations of these approaches that can be addressed via Key Biodiversity Areas (KBA). Hence, the aim of the study is to review and compare several current conservation approaches in Malaysia with KBA. Systematic literature search was done using a set of keywords in search engine and visited official government websites to obtain relevant documentations on conservation and biodiversity in Malaysia. Based on the findings, KBA is a holistic approach consisting of several biodiversity elements, criteria and themes that can be put in place, including Important Plant Areas (IPA), Important Bird and Biodiversity Areas (IBA), Important Fungus Areas and Prime Butterfly Areas. This approach has successfully helped many countries such as the Philippines, Indo-Burma hotspot, Uganda, and Canada identify and prioritize important sites for biodiversity conservation. Thus, KBA approach is an alternative approach to support stakeholders in mainstreaming biodiversity conservation approaches in Malaysia for more effective conservation planning in the future. This approach also offers geographic targets for the expansion of protected area coverage and identifies the site for urgent conservation action.
Managing and protecting of endangered Rafflesia species in Kelantan, Peninsular Malaysia
Authors: Fauzan M , Muhammad-Hapiz A M , Azizul R , Rosilan S , Hamidi A H , Zahari I , Aweng E R , Mohamad-Faiz M A , Abas M A , Kamarul-Ariffin H , Nor-Hizami H , Mohammad-Firdaus A K , Susatya A , Zulhazman H
Published: September 2021

Rafflesia is the most magnificent and largest flower in the world. In Southeast Asia, the species becoming endangered due to anthropogenic activities such as logging, conversion of forest into large-scale agricultural areas, urbanization and unsustainable ecotourism. This paper has specifically highlighted the efforts that have been taken by the Kelantan State Forestry Department (KFD) in ensuring the sustainability and survival of this gigantic flower in its natural habitat. A survey by Universiti Malaysia Kelantan (UMK) shows that many populations of Rafflesia were situated in the forest reserves under the administration of KFD, such as in Lojing, Mt. Chamah, Mt. Basor and Mt. Stong. A lot of initiatives have been implemented by KFD such as organising scientific expeditions and the establishment of the High Conservation Value Forest (HCVF). In July 2011, the State Government of Kelantan declared an area of 404 ha (1,000 acres) bordering Sg. Berok Forest Reserve in Lojing Highlands as the Rafflesia Preservation Area. This recognition by the state government resulted from collaboration efforts of UMK, KFD and South Kelantan Development Authority (KESEDAR). To date, KFD has established a total of two HCVFs in Kelantan and a new area of 50 ha in Compartment 1, Lojing Forest Reserve has also been dedicated for the protection of Rafflesia. This paper was also briefly discussed several issues and challenges in conserving Rafflesia in Kelantan such as the expansion of large-scale agricultural plantation, participation of local community, tourism and income generation, international and internal funds for conservation works, and provide an integrated tourism and management plans. Hopefully, this effort will lead to the establishment of a centre of excellence in nature conservation, ecotourism and scientific research of Rafflesia in Kelantan.
Pre-treatment of Black Soldier Fly Larvae (BSFL) using neutral salt to improve protein digestibility of Macrobrachium rosenbergii feed
Authors: Muhammad Amiruddin W , Siti Zarin Sofia A M , Al-Amsyar S M , Rusli N D , Mat K B , Muhamad Sukri S A , Mohd M , Harun H C
Published: September 2021

Macrobrachium rosenbergii (M. rosenbergii) is one of the economically driven freshwater aquaculture species in many countries. The production of M. rosenbergii has been increased over the year. Along with the growth of production of aquaculture species, feed production also rises. Artemia nauplii are the main live feed with partial replacement with egg custard. However, the application of live feed is costly. Black Soldier Fly larvae (BSFL) is a high potential source of protein that can be applied as M. rosenbergii larvae feed. Meanwhile, pre-treatment of BSFL using neutral salt (NaCl and KCl) is essential to improve the protein digestibility of M. rosenbergii larvae. This study aims to produce feed that can help in producing fast-growing and healthy M. rosenbergii larvae. Different percentages of salt were at 5%, 10%, and 15% were used for BSFL pre-treatment, while BSFL without the addition of salt was used as a control diet. The present study showed that pre-treated BSFL with 15% KCl had a higher protein decreased among the other treatments, followed by 10% KCl and 15% NaCl. In addition, egg custard with 100% BSFL has the highest crude protein and lipid content, which was higher than control (without BSFL), which has the lowest crude protein and lipid content. This study shows that the formulated egg custard has the optimum nutrient that meets the M. rosenbergii larvae requirement.
Conceptual framework of smart fertilization management for oil palm tree based on IOT and deep learning
Authors: Mohd Adib N A N , Daliman S
Published: September 2021

Oil palm trees contribute economic income to the national and community by generating various types of productions. This will cause an expansion of the area for the plantation of oil palm seeds, then contributes to the stability in distributing good quality oil to accommodate the growing population. Furthermore, degradation occurs when the planting of oil palm trees increases rapidly, especially the occurrence of uncontrolled oil palm cultivation. The degradation can cause loss of soil nutrients due to soil erosion. The lack of macronutrients, Nitrogen (N), Phosphorus (P), Potassium (K) and Magnesium (Mg) on oil palm tree may impact on its growth which includes the quality of crops. Traditional approach to detect macronutrients, can also lead to some improper control in turn leads results in reduction in yield. The existing system has given limited information of dataset and slower classification performance due to limited functions. With the adaptability of Internet of Things (IoT) technologies, oil palm tree growth data and fertilization management can be utilizing effortlessly and effectively. The context of conceptual framework comprises the IoT technologies, image processing, machine learning and deep learning which focuses on environmental factors that affecting the young oil palm tree growth that involve temperature, humidity, soil moisture content, light and nutrient. Thus, a study of IoT, machine learning and deep learning for smart fertilization management of oil palm trees is suggested helping and raise the efficiency of oil palm trees management in Malaysia.
Evaluation on mechanical properties of plywood from two fast growing species: Neolamarckia cadamba and Paraserianthes falcataria
Authors: Rahman W M N W A , Yunus N Y , Sa’ad M F , Amin M F M , Mohamad M A N , Chotikhan A , Ahmad M I , Rasat M S M
Published: September 2021

Neolamarckia cadamba (Laran@Kelampayan) and Paraserianthes falcataria (Batai) are both fast growing species known to be planted in Malaysia for their high growth rate, therefore made as reforestation species. This study had been done in evaluating the mechanical properties of these species as a new wood material for plywood production as an alternative and discovering used for the depleting supply of big diameter log from virgin forest. The tree samples were harvested from trial plot in UiTM Pahang, Bandar Tun Razak Jengka, Pahang, Malaysia and sent to plywood mills nearby for plywood production. Plywood was composed in five layers and seven layers with 12 mm thickness and used melamine urea formaldehyde (MUF) as their binder based on commercial industry production. Panels were cut and tested according to Japanese Agriculture Standard for plywood (JAS 2014) at Forest Research Institute Malaysia (FRIM), Kepong, Selangor, Malaysia. Based on minimum standard requirement, results show that both species were suitable to be used in plywood production for general use and structural (decorative) purpose. In addition, increased veneer layers were improved the panel strength. This study shows those species had potential to be an alternative wood material for plywood industry in Malaysia thus can reduce independency of wood species from virgin forest.
BleTIES: annotation of natural genome editing in ciliates using long read sequencing
Authors: Seah Brandon K B , Swart Estienne C
Published: September 2021

Ciliates are single-celled eukaryotes that eliminate specific, interspersed DNA sequences (internally eliminated sequences, IESs) from their genomes during development. These are challenging to annotate and assemble because IES-containing sequences are typically much less abundant in the cell than those without, and IES sequences themselves often contain repetitive and low-complexity sequences. Long-read sequencing technologies from Pacific Biosciences and Oxford Nanopore have the potential to reconstruct longer IESs than has been possible with short reads but require a different assembly strategy. Here we present BleTIES, a software toolkit for detecting, assembling, and analyzing IESs using mapped long reads.

Availability and implementation

BleTIES is implemented in Python 3. Source code is available at https://github.com/Swart-lab/bleties (MIT license) and also distributed via Bioconda.

Supplementary information

Supplementary data are available at Bioinformatics online.
Analysis of tripartite motif (TRIM) family gene expression in prostate cancer bone metastases
Authors: Offermann Anne , Kang Duan , Watermann Christian , Weingart Anika , Hupe Marie C , Saraji Alireza , Stegmann-Frehse Janine , Kruper Rosemarie , Schüle Roland , Pantel Klaus , Taubert Helge , Duensing Stefan , Culig Zoran , Aigner Achim , Klapper Wolfram , Jonigk Danny , Philipp Kühnel Mark , Merseburger Axel S , Kirfel Jutta , Sailer Verena , Perner Sven
Published: September 2021

Tripartite motif (TRIM) family proteins are post-translational protein modifiers with E3-ubiquitin ligase activity, thereby involved in various biological processes. The molecular mechanisms driving prostate cancer (PCa) bone metastasis (BM) are incompletely understood, and targetable genetic alterations are lacking in the majority of cases. Therefore, we aimed to explore the expression and potential functional relevance of 71 TRIM members in bone metastatic PCa. We performed transcriptome analysis of all human TRIM family members and 770 cancer-related genes in 29 localized PCa and 30 PCa BM using Nanostring. KEGG, STRING and Ubibrowser were used for further bioinformatic gene correlation and pathway enrichment analyses. Compared to localized tumors, six TRIMs are under-expressed while nine TRIMs are over-expressed in BM. The differentially expressed TRIM proteins are linked to TNF-, TGFβ-, PI3K/AKT- and HIF-1-signaling, and to features such as proteoglycans, platelet activation, adhesion and ECM-interaction based on correlation to cancer-related genes. The identification of TRIM-specific E3-ligase-substrates revealed insight into functional connections to oncogenes, tumor suppressors and cancer-related pathways including androgen receptor- and TGFβ signaling, cell cycle regulation and splicing. In summary, this is the first study that comprehensively and systematically characterizes the expression of all TRIM members in PCa BM. Our results describe post-translational protein modification as an important regulatory mechanism of oncogenes, tumor suppressors, and pathway molecules in PCa progression. Therefore, this study may provide evidence for novel therapeutic targets, in particular for the treatment or prevention of BM.
Pradefovir Treatment in Patients With Chronic Hepatitis B: Week 24 Results From a Multicenter, Double-Blind, Randomized, Noninferiority, Phase 2 Trial
Authors: Gao Yanhang , Kong Fei , Song Xinwen , Shang Jia , Yao Lvfeng , Xia Jinyu , Peng Yanzhong , Liu Weidong , Gong Huanyu , Mu Mao , Cui Hesong , Han Tao , Chen Wen , Wu Xiaolu , Yang Yongfeng , Yan Xuebing , Jin Zhenjing , Wang Peng , Zhu Qingjing , Chen Liang , Zhao Caiyan , Zhang Dengke , Jin Weili , Wang Daidi , Wen Xiuhong , Liu Chunmei , Jia Jidong , Mao Qing , Ding Yanhua , Jin Xueyuan , Zhang Zong , Mao Qianguo , Li Guangming , Niu Junqi
Published: September 2021

Background

Pradefovir is a liver-targeted prodrug of adefovir, a nucleoside/nucleotide analogue with antiviral activity against hepatitis B virus (HBV) DNA polymerase. This phase 2 study compared the efficacy and safety of oral pradefovir (30, 45, 60, or 75 mg) versus tenofovir disoproxil fumarate (TDF; 300 mg) and aimed to identify the most appropriate dose of pradefovir for the forthcoming phase 3 study.

Methods

Treatment-naive and experienced (not on treatment >6 months) patients with chronic hepatitis B were eligible.

Results

A total of 240 participants were randomized and treated in the study (48 per group). Approximately 80% were hepatitis B e antigen (HBeAg) positive, and 10% had liver cirrhosis. The reductions from baseline in HBV DNA levels achieved at week 24 were 5.40, 5.34, 5.33, and 5.40 log10 IU/mL, with pradefovir doses of 30-, 45-, 60-, and 75-mg, respectively, compared with 5.12 log10 IU/mL with TDF. However, HBeAg loss was attained by more participants who received 45-, 60-, or 75-mg pradefovir than by those receiving TDF (12%, 6%, and 9% vs 3%). The TDF group exhibited a more significant increase in serum creatinine than the pradefovir 30- and 45-mg groups, and serum phosphate levels were comparable among all groups. Most adverse events (AEs) were mild (grade 1). No treatment-related severe AEs were reported. Overall, AEs and laboratory abnormalities were comparable to those in the TDF group.

Conclusions

Pradefovir and TDF exhibited comparable reductions in HBV DNA levels. All treatments were safe and well tolerated.

Clinical Trials registration

NCT00230503 and China Drug Trials CTR2018042
Patterns of bacterial diversity in embryonic capsules of the spotted salamanderAmbystoma maculatum: an expanding view of a symbiosis
Authors: Bishop Cory , Jurga Emil , Graham Lori
Published: September 2021

The unicellular green alga, Oophila amblystomatis, populates egg capsules of the spotted salamander Ambystoma maculatum. This nutrient-exchange mutualism is widely perceived as a bipartite interaction, but the presence and contributing effects of bacteria to this symbiosis are unknown. We used standard cultivation techniques and amplicon sequencing of the V4/V5 region of 16S rRNA gene to identify and compare diversity of bacterial taxa in embryonic capsules with that in the aquatic breeding habitat. Our sampling regime allowed us to investigate diversity among individual capsules of an egg mass and between two ponds and sampling years. Capsules contain much lower diversity of bacteria than pond water, and spatial and temporal variation in intracapsular and pond bacterial diversity was observed. Despite this variation, sequences corresponding to species in the orders Burkholderiales and Oligoflexales were either prevalent or abundant, or both. Isolates most commonly recovered from capsules were closely related to species in the genus Herbaspirillum (Burkholderiaceae); other isolates were pseudomonads, but in all cases are closely related to known vascular plant-associated species. We conclude that, despite observed variation, there are bacterial taxa whose presence is held in common spatially and temporally among capsules and that the symbiosis between O. amblystomatis and A. maculatum may involve these taxa.
Development of an Haa1-based biosensor for acetic acid sensing in Saccharomyces cerevisiae
Authors: Mormino Maurizio , Siewers Verena , Nygård Yvonne
Published: September 2021

Acetic acid is one of the main inhibitors of lignocellulosic hydrolysates and acetic acid tolerance is crucial for the development of robust cell factories for conversion of biomass. As a precursor of acetyl-coenzyme A, it also plays an important role in central carbon metabolism. Thus, monitoring acetic acid levels is a crucial aspect when cultivating yeast. Transcription factor-based biosensors represent useful tools to follow metabolite concentrations. Here, we present the development of an acetic acid biosensor based on the Saccharomyces cerevisiae transcription factor Haa1 that upon binding to acetic acid relocates to the nucleus. In the biosensor, a synthetic transcription factor consisting of Haa1 and BM3R1 from Bacillus megaterium was used to control expression of a reporter gene under a promoter containing BM3R1 binding sites. The biosensor did not drive expression under a promoter containing Haa1 binding sites and responded to acetic acid over a linear range spanning from 10 to 60 mM. To validate its applicability, the biosensor was integrated into acetic acid-producing strains. A direct correlation between biosensor output and acetic acid production was detected. The developed biosensor enables high-throughput screening of strains producing acetic acid and could also be used to investigate acetic acid-tolerant strain libraries.
Microtremor surveys based on rotational seismology: theoretical analysis with focus on separation of Rayleigh and Love waves in general wavefield of microtremors
Authors: Cho I , Yoshida K , Uebayashi H
Published: September 2021

The applicability of rotational seismology to the general wavefield of microtremors is theoretically demonstrated based on a random process model of a 2-D wavefield. We show the effectiveness of taking the rotations (i.e. spatial differentiation) of microtremor waveforms in separating the Rayleigh and Love waves in a wavefield where waves are simultaneously arriving from various directions with different intensities. This means that a method based on rotational seismology (a rotational method) is capable of separating Rayleigh and Love waves without adopting a specific array geometry or imposing a specific assumption on the microtremor wavefield. This is an important feature of a rotational method because the spatial autocorrelation (SPAC) method, a conventional approach for determining phase velocities in microtremor array surveys, requires either the use of a circular array or the assumption of an isotropic wavefield (i.e. azimuthal averaging of correlations is required). Derivatives of the SPAC method additionally require the assumption that Rayleigh and Love waves are uncorrelated. We also show that it is possible to apply a rotational method to determine the characteristics of Love waves based on a simple three-point microtremor array that consists of translational (i.e. ordinary) three-component sensors. In later sections, we assume realistic data processing for microtremor arrays with translational sensors to construct a theoretical model to evaluate the effects of approximating spatial differentiation via finite differencing (i.e. array-derived rotation, ADR) and the effects of incoherent noise on analysis results. Using this model, it is shown that in a short-wavelength range compared to the distance for finite differencing (e.g. $\lambda < 3h$, where $\lambda $ and $h$ are the wavelength and distance for finite differencing, respectively), the leakage of unwanted wave components can determine the analysis limit. It is also shown that in a long-wavelength range (e.g. $\lambda > 3h$), the signal intensity gradually decreases, and thus the effects of incoherent noise increase (i.e. the signal-to-noise ratio, SNR decreases) and determine the analysis limit. We derive the relation between the SNR and wavelength. Although the analysis results quantitatively depend on the array geometry used for finite differencing, the qualitative understanding supported by mathematical expressions with a physically clear meaning can serve as a guideline for the treatment of data obtained from ADR.
Assessing the role of selected constraints in Bayesian dynamic source inversion: application to the 2017Mw 6.3 Lesvos earthquake
Authors: Kostka Filip , Zahradník Jiří , Sokos Efthimios , Gallovič František
Published: September 2021

A dynamic finite-fault source inversion for stress and frictional parameters of the Mw 6.3 2017 Lesvos earthquake is carried out. The main shock occurred on June 12, offshore the southeastern coast of the Greek island of Lesvos in the north Aegean Sea. It caused 1 fatality, 15 injuries, and extensive damage to the southern part of the island. Dynamic rupture evolution is modelled on an elliptic patch, using the linear slip-weakening friction law. The inversion is posed as a Bayesian problem and the Parallel Tempering Markov Chain Monte Carlo algorithm is used to obtain posterior probability distributions by updating the prior distribution with progressively more constraints. To calculate the first posterior distribution, only the constraint that the model should expand beyond the nucleation patch is used. Then, we add the constraint that the model should reach a moment magnitude similar to that obtained from our centroid moment tensor inversion. For the final posterior distribution, 15 acceleration records from Greek and Turkish strong motion networks at near regional distances (≈ 30–150 km) in the frequency range of 0.05–0.15 Hz are used. The three posterior distributions are compared to understand how much each constraint contributes to resolving different quantities. The most probable values and uncertainties of individual parameters are also calculated, along with their mutual trade-offs. The features best determined by seismograms in the final posterior distribution include the position of the nucleation region, the mean direction of rupture (towards WNW), the mean rupture speed (with 68 per cent of the distribution lying between 1.4 and 2.6 km s–1), radiated energy (12–65 TJ), radiation efficiency (0.09–0.38) and the mean stress drop (2.2–6.5 MPa).
Understanding the ‘crisis of the institution’ in the liberal trade order at the WTO
Authors: Sinha Aseema
Published: September 2021

The liberal trade order is in crisis. I argue that the origins of the current crises lie in the underlying tension which exists in the World Trade Organization (WTO), magnified by a churning in global power dynamics. A dilemma at the heart of the WTO between two important goals of representativeness and effectiveness means that both goals cannot be pursued at the same time. Now, this inherent tension is being magnified by power shifts in the global economy most evident in the rise of emerging powers within the WTO, who demand more representation, and the retreat by the US towards a more inward-looking orientation; both together damage effectiveness. Simultaneously, new powers such as China and India are defending a ‘reformed multilateralism’ combined with selective protectionism with varying capacity. These shifts are transforming previous ‘crises within institutions’ into a ‘crisis of institutions’ at the WTO, wherein the rules of the game, ideas of free trade and the legitimacy of the WTO are under threat. Global trade politics is seeing new coalitions at the WTO, as emerging powers craft their own rise, US defends sovereignty and trade protections, and launches a challenge to China's rise, and some established powers (the EU for example) seek to reform it. The new global trade politics is walking on two uneven legs and creating winners and losers and new ways of managing the transitional trading order as did the creation of the post-world war order.
Globalization, deglobalization and the liberal international order
Authors: Kornprobst Markus , Paul T V
Published: September 2021

For decades, globalization and the liberal international order evolved side by side. Recently, however, deglobalizing forces have been on the rise and the liberal international order has come to be increasingly beleaguered. The special issue ‘Deglobalization? The future of the liberal international order’ examines the interconnectedness of globalization and deglobalization processes on the one hand and the trajectory of the liberal international order on the other. This introduction provides a conceptual frame for the articles to follow. It discusses globalization and deglobalization processes, compares how they have been intertwined with the liberal international order in the past and presently, and explores how these differences are likely to affect the future of world politics. The special issue makes three important contributions. First, we examine globalization and deglobalization processes systematically. Second, we break new ground in studying the future of international order. Third, we generate novel insights into epochal change.
Seeing Red: representing a mark consisting of a colour combination
Authors: Martin Stefan , Boyd Jonathan
Published: September 2021

General Court, T-193/18, Andreas Stihl v EUIPO, EU:T:2021:163, 24 March 2021

In its first judgment since the decision of the Court of Justice of the European Union (‘CJEU’) in the Red Bull case (C-124/18 P), the General Court has clarified its approach to colour marks and Article 4 of the EU Trade Mark Regulation 2017/1001 (‘EUTMR’).
Persuasive Message Pretesting Using Non-Behavioral Outcomes: Differences in Attitudinal and Intention Effects as Diagnostic of Differences in Behavioral Effects
Authors: O’Keefe Daniel J
Published: September 2021

Persuasive message designers would like to be able to pretest messages to see which will be more effective in influencing behavioral outcomes, but pretesting using behavioral measures is commonly not practical. Examination of within-study effect size comparisons from 317 studies of 22 message variations suggests that persuasive messages’ relative effectiveness is strikingly similar across attitudinal, intention, and behavioral outcomes—with messages’ relative persuasiveness with respect to intention outcomes especially indicative of relative persuasiveness with respect to behavioral outcomes. Intention measures thus provide a convenient and accurate means of persuasive message pretesting.
The Distorting Prism of Social Media: How Self-Selection and Exposure to Incivility Fuel Online Comment Toxicity
Authors: Kim Jin Woo , Guess Andrew , Nyhan Brendan , Reifler Jason
Published: September 2021

Though prior studies have analyzed the textual characteristics of online comments about politics, less is known about how selection into commenting behavior and exposure to other people’s comments changes the tone and content of political discourse. This article makes three contributions. First, we show that frequent commenters on Facebook are more likely to be interested in politics, to have more polarized opinions, and to use toxic language in comments in an elicitation task. Second, we find that people who comment on articles in the real world use more toxic language on average than the public as a whole; levels of toxicity in comments scraped from media outlet Facebook pages greatly exceed what is observed in comments we elicit on the same articles from a nationally representative sample. Finally, we demonstrate experimentally that exposure to toxic language in comments increases the toxicity of subsequent comments.
The small GTPase NtRHO1 negatively regulates tobacco defense response to tobacco mosaic virus by interacting with NtWRKY50
Authors: Han Hongyan , Zou Jialing , Zhou Jingya , Zeng Mengyuan , Zheng Dongchao , Yuan Xuefeng , Xi Dehui
Published: September 2021

Small GTPases play critical roles in the regulation of plant growth and development. However, the mechanism of action of small GTPases in plant response to virus infection remains largely unknown. Here, the gene encoding a Rho-type GTPase, NtRHO1, was identified as one of the genes up-regulated after tobacco mosaic virus (TMV) infection. Subcellular localization of NtRHO1 showed that it was located in the cytoplasm, plasma membrane, and nucleus. Transient overexpression of NtRHO1 in Nicotiana benthamiana accelerated TMV reproduction and led to the production of reactive oxygen species. By contrast, silencing of NtRHO1 reduced the sensitivity of N. benthamiana to TMV-GFP. Further exploration revealed a direct interaction between NtRHO1 and NtWRKY50, a positive regulator of the N. benthamiana response to virus infection. Yeast one-hybrid and electrophoretic mobility shift assays showed that this regulation was related to the capacity of NtWRKY50 to bind to the WK-box of the PR1 promoter, which was weakened by the interaction between NtRHO1 and NtWRKY50. Thus, our results indicate that the small GTPase NtRHO1 plays a negative role in tobacco response to TMV infection by interacting with transcription factor NtWRKY50, resulting in reduced plant immunity.
Arabidopsis PAP17 is a dual-localized purple acid phosphatase up-regulated during phosphate deprivation, senescence, and oxidative stress
Authors: O’Gallagher Bryden , Ghahremani Mina , Stigter Kyla , Walker Emma J L , Pyc Michal , Liu Ang-Yu , MacIntosh Gustavo C , Mullen Robert T , Plaxton William C
Published: September 2021

A 35 kDa monomeric purple acid phosphatase (APase) was purified from cell wall extracts of Pi starved (–Pi) Arabidopsis thaliana suspension cells and identified as AtPAP17 (At3g17790) by mass spectrometry and N-terminal microsequencing. AtPAP17 was de novo synthesized and dual-localized to the secretome and/or intracellular fraction of –Pi or salt-stressed plants, or senescing leaves. Transiently expressed AtPAP17–green fluorescent protein localized to lytic vacuoles of the Arabidopsis suspension cells. No significant biochemical or phenotypical changes associated with AtPAP17 loss of function were observed in an atpap17 mutant during Pi deprivation, leaf senescence, or salinity stress. Nevertheless, AtPAP17 is hypothesized to contribute to Pi metabolism owing to its marked up-regulation during Pi starvation and leaf senescence, broad APase substrate selectivity and pH activity profile, and rapid repression and turnover following Pi resupply to –Pi plants. While AtPAP17 also catalyzed the peroxidation of luminol, which was optimal at pH 9.2, it exhibited a low Vmax and affinity for hydrogen peroxide relative to horseradish peroxidase. These results, coupled with absence of a phenotype in the salt-stressed or –Pi atpap17 mutant, do not support proposals that the peroxidase activity of AtPAP17 contributes to the detoxification of reactive oxygen species during stresses that trigger AtPAP17 up-regulation.
Predicting halo occupation and galaxy assembly bias with machine learning
Authors: Xu Xiaoju , Kumar Saurabh , Zehavi Idit , Contreras Sergio
Published: September 2021

Understanding the impact of halo properties beyond halo mass on the clustering of galaxies (namely galaxy assembly bias) remains a challenge for contemporary models of galaxy clustering. We explore the use of machine learning to predict the halo occupations and recover galaxy clustering and assembly bias in a semi-analytic galaxy formation model. For stellar mass selected samples, we train a random forest algorithm on the number of central and satellite galaxies in each dark matter halo. With the predicted occupations, we create mock galaxy catalogues and measure the clustering and assembly bias. Using a range of halo and environment properties, we find that the machine learning predictions of the occupancy variations with secondary properties, galaxy clustering, and assembly bias are all in excellent agreement with those of our target galaxy formation model. Internal halo properties are most important for the central galaxies prediction, while environment plays a critical role for the satellites. Our machine learning models are all provided in a usable format. We demonstrate that machine learning is a powerful tool for modelling the galaxy–halo connection, and can be used to create realistic mock galaxy catalogues which accurately recover the expected occupancy variations, galaxy clustering, and galaxy assembly bias, imperative for cosmological analyses of upcoming surveys.