bluuebunny/crossref_metadata_2025 huggingface dataset:
A framework to efficiently smoothL1penalties for linear regression
Authors: Hahn Georg , Lutz Sharon M. , Laha Nilanjana , Lange Christoph
Published: September 2020

Penalized linear regression approaches that include anL1term have become an important tool in statistical data analysis. One prominent example is the least absolute shrinkage and selection operator (Lasso), though the class ofL1penalized regression operators also includes the fused and graphical Lasso, the elastic net, etc. Although theL1penalty makes their objective function convex, it is not differentiable everywhere, motivating the development of proximal gradient algorithms such as Fista, the current gold standard in the literature. In this work, we take a different approach based on smoothing in a fixed parameter setting (the problem sizenand number of parameterspare fixed). The methodological contribution of our article is threefold: (1) We introduce a unified framework to compute closed-form smooth surrogates of a whole class ofL1penalized regression problems using Nesterov smoothing. The surrogates preserve the convexity of the original (unsmoothed) objective functions, are uniformly close to them, and have closed-form derivatives everywhere for efficient minimization via gradient descent; (2) We prove that the estimates obtained with the smooth surrogates can be made arbitrarily close to the ones of the original (unsmoothed) objective functions, and provide explicitly computable a priori error bounds on the accuracy of our estimates; (3) We propose an iterative algorithm to progressively smooth theL1penalty which increases accuracy and is virtually free of tuning parameters. The proposed methodology is applicable to a large class ofL1penalized regression operators, including all the operators mentioned above. Although the resulting estimates are typically dense, sparseness can be enforced again via thresholding. Using simulation studies, we compare our framework to current gold standards such as Fista, glmnet, gLasso, etc. Our results suggest that our proposed smoothing framework provides predictions of equal or higher accuracy than the gold standards while keeping the aforementioned theoretical guarantees and having roughly the same asymptotic runtime scaling.
DNABERT: pre-trained Bidirectional Encoder Representations from Transformers model for DNA-language in genome
Authors: Ji Yanrong , Zhou Zhihan , Liu Han , Davuluri Ramana V
Published: September 2020

Deciphering the language of non-coding DNA is one of the fundamental problems in genome research. Gene regulatory code is highly complex due to the existence of polysemy and distant semantic relationship, which previous informatics methods often fail to capture especially in data-scarce scenarios. To address this challenge, we developed a novel pre-trained bidirectional encoder representation, named DNABERT, that forms global and transferrable understanding of genomic DNA sequences based on up and downstream nucleotide contexts. We show that the single pre-trained transformers model can simultaneously achieve state-of-the-art performance on many sequence predictions tasks, after easy fine-tuning using small task-specific data. Further, DNABERT enables direct visualization of nucleotide-level importance and semantic relationship within input sequences for better interpretability and accurate identification of conserved sequence motifs and functional genetic variants. Finally, we demonstrate that pre-trained DNABERT with human genome can even be readily applied to other organisms with exceptional performance.
scIntegral: A scalable and accurate cell-type identification method for scRNA-seq data with application to integration of multiple donors
Authors: Lee Hanbin , Kim Chanwoo , Jeong Juhee , Jung Keehoon , Han Buhm
Published: September 2020

We presentscIntegral, a scalable and accurate method to identify cell types in scRNA data. Our method probabilistically identifies cell-types of the cells in a semi-supervised manner using marker list information as prior. scIntegral is more accurate than existing state-of-the-art methods, reducing the error rate by up to three-folds in real data. scIntegral can precisely identify very rare (<0.5%) cell populations, suggesting utilities forin-silicocell extraction. A notable application of scIntegral is to systematically integrate scRNA-seq data of multiple donors with strong heterogeneity and batch effects. scIntegral is extremely efficient and takes only an hour to integrate ten thousand donor data, while fully accounting for heterogeneity with covariates. Many previous methods focused on integrating multi-sample data in the cluster level, but it was challenging to quantitatively measure the benefit of integration. We show that integrating multiple donors can significantly reduce the error rate in cell-type identification, when measured with respect to the gold standard cell labels. scIntegral is freely available athttps://github.com/hanbin973/scIntegral.
Neural encoding of the reliability of directional information during the preparation of targeted movements
Authors: Tzagarakis Charidimos , West Sarah , Pellizzer Giuseppe
Published: September 2020

Visual information about the location of an upcoming target can be used to prepare an appropriate motor response and reduce its reaction time. Here, we investigated the brain mechanisms associated with the reliability of directional information used for motor preparation. We recorded brain activity using magnetoencephalography (MEG) during a delayed reaching task in which a visual cue provided valid information about the location of the upcoming target with 50, 75 or 100% reliability. We found that reaction time increased as cue reliability decreased and that trials with invalid cues had longer reaction times than trials with valid cues. MEG channel analysis showed that during the late cue period the power of the beta-band from left mid-anterior channels, contralateral to the responding hand, correlated with the reliability of the cue. This effect was source localized over a large motor-related cortical and subcortical network. In addition, during invalid-cue trials there was a phasic increase of theta-band power following target onset from left posterior channels, localized to the left occipito-parietal cortex. Furthermore, the theta-beta cross-frequency coupling between left mid-occipital and motor cortex transiently increased before responses to invalid-cue trials. In conclusion, beta-band power in motor-related areas reflected the reliability of directional information used during motor preparation, whereas phasic theta-band activity may have signaled whether the target was at the expected location or not. These results elucidate mechanisms of interaction between attentional and motor processes.
Graded spikes differentially signal neurotransmitter input in cerebrospinal fluid contacting neurons of the mouse spinal cord
Authors: Johnson Emily , Clark Marilyn , Oncul Merve , MacLean Claudia , Deuchars Jim , Deuchars Susan A. , Johnston Jamie
Published: September 2020

The action potential and its all-or-none nature is fundamental to neural communication. Canonically the action potential is initiated once voltage-gated Na+channels are activated, and their rapid kinetics of activation and inactivation give rise to the action potential’s all-or-none nature. Here we show that cerebrospinal fluid contacting neurons (CSFcNs) surrounding the central canal of the mouse spinal cord employ a different strategy. Rather than using voltage-gated Na+channels to generate binary spikes, CSFcNs use two different types of voltage-gated Ca2+channel, enabling spikes of different amplitude. T-type Ca2+channels generate small amplitude spikes, whereas large amplitude spikes require high voltage-activated Cd2+sensitive Ca2+channels. We show that these different amplitude spikes signal input from different transmitter systems; purinergic inputs evoke smaller T-type dependent spikes while cholinergic inputs evoke large T-type independent spikes. Different synaptic inputs to CSFcNs can therefore be signalled by the spike amplitude.
ALPACA: a fast and accurate approach for automated landmarking of three-dimensional biological structures
Authors: Porto Arthur , Rolfe Sara M. , Maga A. Murat
Published: September 2020

Landmark-based geometric morphometrics has emerged as an essential discipline for the quantitative analysis of size and shape in ecology and evolution. With the ever-increasing density of digitized landmarks, the possible development of a fully automated method of landmark placement has attracted considerable attention. Despite the recent progress in image registration techniques, which could provide a pathway to automation, three-dimensional morphometric data is still mainly gathered by trained experts. For the most part, the large infrastructure requirements necessary to perform image-based registration, together with its system-specificity and its overall speed have prevented wide dissemination.

Here, we propose and implement a general and lightweight point cloud-based approach to automatically collect highdimensional landmark data in 3D surfaces (Automated Landmarking through Point cloud Alignment and Correspondence Analysis). Our framework possesses several advantages compared with image-based approaches. First, it presents comparable landmarking accuracy, despite relying on a single, random reference specimen and much sparser sampling of the structure’s surface. Second, it is performant such that it can be efficiently run on consumer-grade personal computers. Finally, it is general and can be applied to any biological structure of interest, regardless of whether anatomical atlases are available.

Our validation procedures indicate that the method is capable of recovering multivariate patterns of morphological variation that are largely indistinguishable from those obtained by manual digitization, indicating that the use of an automated landmarking approach should not result in different conclusions regarding the nature of multivariate patterns of morphological variation.

The proposed point cloud-based approach has the potential to increase the scale and reproducibility of morphometrics research. To allow ALPACA to be used out-of-the-box by users with no prior programming experience, we implemented it as a module as part of the SlicerMorph project. SlicerMorph is an extension that enables geometric morphometrics data collection and 3D specimen analysis within the open-source 3D Slicer biomedical visualization ecosystem. We expect that convenient access to this platform will make ALPACA broadly applicable within ecology and evolution.
Single-cell analysis of prostaglandin E2-induced decidual cell differentiation: does extracellular 8-Br-cAMP cause artifacts?
Authors: Stadtmauer Daniel J. , Wagner Günter P.
Published: September 2020

Development of the uterine decidua, the transient maternal tissue contacting the fetus during extended gestation, is the hallmark of reproduction in many placental mammals. Differentiation of decidual stromal cells is known to be induced by stimuli that activate the nuclear progesterone receptor and the cyclic AMP/protein kinase A (cAMP/PKA) pathways. The nature of the stimulus upstream of PKA has not been clearly defined, although a number of candidates have been proposed. To bypass this uncertainty for in vitro experiments, direct addition of membrane-permeable cAMP along with progestin has been the prevailing method. Phylogenetic inference suggests that the inflammatory eicosanoid prostaglandin E2 (PGE2) was the stimulus that ancestrally induced decidualization. Accordingly, we developed a protocol to decidualize human endometrial stromal fibroblasts using progestin and PGE2 and analyzed the response in comparison with a cAMP-based protocol. Transcriptomic comparison reveals a common activation of core decidual cell genes between both treatments, and a set of senescence-related genes exaggerated under cAMP treatment. Single-cell transcriptomic analysis of PGE2-mediated decidualization revealed a major transcriptomic transition between an early activated cell state and a differentiated decidual state, but notably did not identify a developmental trajectory representing a distinct senescent decidual state as reported in recent literature. Furthermore, investigation of the signal transduction process underlying PGE2-mediated decidualization showed that it depends upon progestin-dependent induction of PGE2 receptor 2 (PTGER2 aka EP2) and PKA, the kinase activated by PTGER2. This progesterone-dependent induction of PTGER2 is absent in the opossum, a species incapable of decidualization. Together, these findings suggest that the origin of the decidual cell type involved the evolution of progesterone-dependent activation of the PGE2/EP2/PKA axis. We propose the use of PGE2 for in vitro decidualization studies as a potentially more physiological model than 8-Br-cAMP.
Potent activation of SARM1 by NMN analogue VMN underlies vacor neurotoxicity
Authors: Loreto Andrea , Angeletti Carlo , Gu Weixi , Osborne Andrew , Nieuwenhuis Bart , Gilley Jonathan , Arthur-Farraj Peter , Merlini Elisa , Amici Adolfo , Luo Zhenyao , Hartley-Tassell Lauren , Ve Thomas , Desrochers Laura M. , Wang Qi , Kobe Bostjan , Orsomando Giuseppe , Coleman Michael P.
Published: September 2020

Axon loss underlies symptom onset and progression in many neurodegenerative disorders. Axon degeneration in injury and disease is promoted by activation of the nicotinamide adenine dinucleotide (NAD)-consuming enzyme SARM1 (sterile alpha and TIR motif-containing protein 1). Here, we report vacor mononucleotide (VMN), a metabolite of the pesticide and neurotoxin vacor, as the most potent yet SARM1 activator. Removal of SARM1 shows complete rescue from vacor-induced neuron and axon deathin vitroandin vivo. We present the crystal structure of VMN bound to theDrosophilaSARM1 regulatory armadillo-repeat domain, thus facilitating drug development to prevent SARM1 activation in human disease. This study indicates the likely mechanism of action of vacor as a pesticide and lethal neurotoxin in humans, provides important new tools for drug discovery, and further demonstrates that SARM1 removal can permanently block programmed axon death specifically induced by toxicity as well as genetic mutation.
Metagenomic insights into ecosystem function in the microbial mats of Blue Holes, Shark Bay
Authors: Kindler Gareth S , Wong Hon Lun , Larkum Anthony W D , Johnson Michael , MacLeod Fraser I , Burns Brendan P
Published: September 2020

Microbial mat ecosystems vary in complexity and structure depending on the environmental constraints placed by nature. Here, we describe in detail for the first time the community composition and functional potential of the microbial mats found in the supratidal, gypsum-rich, and hypersaline region of Blue Holes, Shark Bay. This was achieved via high throughput sequencing of total mat community DNA on the Illumina NextSeq platform. Mat communities were mainly comprised of Proteobacteria (29%), followed by Bacteroidetes/Chlorobi Group (11%), and Planctomycetes (10%). These mats were found to also harbor a diverse community of potentially novel microorganisms including members from the DPANN and Asgard archaea, Candidate Phyla Radiation (CPR) and other candidate phyla, with highest diversity indices found in the lower regions of the mat. Major metabolic cycles belonging to sulfur, carbon, nitrogen, and fermentation were detected in the mat metagenomes with the assimilatory sulfate reduction pathway being distinctly abundant. Critical microbial interactions were also inferred, and from 117 medium-to-high quality metagenome-assembled genomes (MAGs), viral defense mechanisms (CRISPR, BREX, and DISARM), elemental transport, osmoprotection, heavy metal and UV resistance were also detected in the mats. These analyses have provided a greater understanding of these distinct mat systems in Shark Bay, including key insights into adaptive responses.
Long-term cellulose enrichment selects for highly cellulolytic consortia and competition for public goods
Authors: Lewin Gina R. , Davis Nicole M. , McDonald Bradon R. , Book Adam J. , Chevrette Marc G. , Suh Steven , Boll Ardina , Currie Cameron R.
Published: September 2020

The complexity of microbial communities hinders our understanding of how microbial diversity and microbe-microbe interactions impact community functions. Here, using six independent communities originating from the refuse dumps of leaf-cutter ants and enriched using the plant polymer cellulose as the sole source of carbon, we examine how changes in bacterial diversity and interactions impact plant biomass decomposition. Over up to 60 serial transfers (∼8 months), cellulolytic ability increased then stabilized in four enrichment lines and was variable in two lines. Bacterial community characterization using 16S rRNA gene amplicon sequencing showed community succession differed between the highly cellulolytic and variably cellulolytic enrichment lines. Metagenomic and metatranscriptomic analyses revealed thatCellvibrioand/orCellulomonasdominated each enrichment line and produced the majority of cellulase enzymes, while diverse taxa were retained within these communities over the duration of transfers. Interestingly, the less cellulolytic communities had a higher diversity of organisms competing for the cellulose breakdown product cellobiose, suggesting that cheating slowed cellulose degradation. In addition, we found competitive exclusion as an important factor shaping all the communities, with the mutual exclusion of specific cellulolytic taxa within individual enrichment lines and the high expression of genes associated with the production of antagonistic compounds. Our results provide insights into how microbial diversity and competition affect the stability and function of cellulose-degrading communities.

Importance

Microbial communities are a key driver of the carbon cycle through the breakdown of complex polysaccharides in diverse environments including soil, marine systems, and the mammalian gut.However, due to the complexity of these communities, the species-species interactions that impact community structure and ultimately shape the rate of decomposition are difficult to define. Here we performed serial enrichment on cellulose using communities inoculated from leaf-cutter ant refuse dumps, a cellulose-rich environment. By concurrently tracking cellulolytic ability and community composition and through metagenomic and metatranscriptomic sequencing, we analyzed the ecological dynamics of the enrichment lines. Our data suggest that antagonism is prevalent in these communities and that competition for soluble sugars may slow degradation and lead to community instability. Together, these results help reveal the relationships between competition and polysaccharide decomposition, with implications in diverse areas ranging from microbial community ecology to cellulosic biofuels production.
An immunodominance hierarchy exists in CD8+T cell responses to HLA-A*02:01-restricted epitopes identified from the non-structural polyprotein 1a of SARS-CoV-2
Authors: Takagi Akira , Matsui Masanori
Published: September 2020

COVID-19 vaccines are being rapidly developed and human trials are underway. Almost all of these vaccines have been designed to induce antibodies targeting spike protein of SARS-CoV-2 in expectation of neutralizing activities. However, non-neutralizing antibodies are at risk of causing antibody-dependent enhancement. Further, the longevity of SARS-CoV-2-specific antibodies is very short. Therefore, in addition to antibody-induced vaccines, novel vaccines on the basis of SARS-CoV-2-specific cytotoxic T lymphocytes (CTLs) should be considered in the vaccine development. Here, we attempted to identify HLA-A*02:01-restricted CTL epitopes derived from the non-structural polyprotein 1a of SARS-CoV-2. Eighty-two peptides were firstly predicted as epitope candidates on bioinformatics. Fifty-four in 82 peptides showed high or medium binding affinities to HLA-A*02:01. HLA-A*02:01 transgenic mice were then immunized with each of the 54 peptides encapsulated into liposomes. The intracellular cytokine staining assay revealed that 18 out of 54 peptides were CTL epitopes because of the induction of IFN-γ-producing CD8+T cells. In the 18 peptides, 10 peptides were chosen for the following analyses because of their high responses. To identify dominant CTL epitopes, mice were immunized with liposomes containing the mixture of the 10 peptides. Some peptides were shown to be statistically predominant over the other peptides. Surprisingly, all mice immunized with the liposomal 10 peptide mixture did not show the same reaction pattern to the 10 peptides. There were three pattern types that varied sequentially, suggesting the existence of an immunodominance hierarchy, which may provide us more variations in the epitope selection for designing CTL-based COVID-19 vaccines.

Importance

For the development of vaccines based on SARS-CoV-2-specific cytotoxic T lymphocytes (CTLs), we attempted to identify HLA-A*02:01-restricted CTL epitopes derived from the non-structural polyprotein 1a of SARS-CoV-2. Out of 82 peptides predicted on bioinformatics, 54 peptides showed good binding affinities to HLA-A*02:01. Using HLA-A*02:01 transgenic mice, 18 in 54 peptides were found to be CTL epitopes in the intracellular cytokine staining assay. Out of 18 peptides, 10 peptides were chosen for the following analyses because of their high responses. To identify dominant epitopes, mice were immunized with liposomes containing the mixture of the 10 peptides. Some peptides were shown to be statistically predominant. Surprisingly, all immunized mice did not show the same reaction pattern to the 10 peptides. There were three pattern types that varied sequentially, suggesting the existence of an immunodominance hierarchy, which may provide us more variations in the epitope selection for designing CTL-based COVID-19 vaccines.
Rapid transition to distance learning due to COVID-19: Perceptions of postgraduate dental learners and instructors
Authors: Rad Fatemeh Amir , Otaki Farah , Baqain Zaid , Zary Nabil , Al-Halabi Manal
Published: September 2020

The outbreak of COVID-19 necessitated abrupt transition from on campus, face-to- face sessions to online, distance learning in higher education institutions. The purpose of this study was to investigate the perceptions of postgraduate dental learners and instructors about the transition to distance learning, including the changes to the learning and teaching and its efficaciousness.

A mixed-methods approach to research was utilized. All the instructors and postgraduate learners were invited to participate in the online survey. Quantitative data was analyzed using descriptive and inferential analyses on SPSS for Windows version 25.0, and for the responses to the open-ended questions, multi-staged Thematic Analysis was utilized.

Both groups of stakeholders: learners and instructors, were quite satisfied with the rapid transition to distance learning due to COVID-19. Instructors were significantly more satisfied than the learners. The stakeholders adapted well to the change. The perception of the stakeholders regarding the case-based scenarios significantly influenced their level of satisfaction. As perceived by the stakeholders, the transition to distance learning entailed advantages and challenges. Going through the experience equipped the stakeholders with lessons learned and enabled them to develop informed opinions of how best to sustain learning and teaching irrespective of how matters unfold in relation to the pandemic.

In conclusion, the worldwide dental education community faced unprecedented challenges due to the onset of COVID-19. Yet, in the grand scheme of things, it is important for decision-makers not to miss-out on the worthwhile opportunities, inherent in the experience, to reinforce curriculums, and maximize the learning and teaching.
A empirical comparison of preservation methods for synthetic DNA data storage
Authors: Organick Lee , Nguyen Bichlien H. , McAmis Rachel , Chen Weida D. , Kohll A. Xavier , Ang Siena Dumas , Grass Robert N. , Ceze Luis , Strauss Karin
Published: September 2020

Synthetic DNA has recently risen as a viable alternative for long-term digital data storage. To ensure that information is safely recovered after storage, it is essential to appropriately preserve the physical DNA molecules encoding the data. While preservation of biological DNA has been studied previously, synthetic DNA differs in that it is typically much shorter in length, it has different sequence profiles with fewer, if any, repeats (or homopolymers), and it has different contaminants. In this paper we evaluate nine different methods used to preserve data files encoded in synthetic DNA by accelerated aging of nearly 29,000 DNA sequences. In addition to a molecular count comparison, we also sequence and analyze the DNA after aging. Our findings show that errors and erasures are stochastic and show no practical distribution difference between preservation methods. Finally, we compare the physical density of these methods and provide a stability versus density trade-offs discussion.
Measurement of Kinetics of Hammerhead Ribozyme Cleavage Reactions using Toehold Mediated Strand Displacement
Authors: Kapadia Jay Bhakti , Kharma Nawwaf , Davis Alen Nellikulam , Kamel Nicolas , Perreault Jonathan
Published: September 2020

This paper presents a probe comprising a fluorophore and a quencher, enabling measurement of hammerhead ribozyme cleavage reactions, without labeled RNA molecules, regular sampling or use of polyacrylamide gels. The probe is made of two DNA strands; one strand is labelled with a fluorophore at its 5’-end, while the other strand is labelled with a quencher at its 3’-end. These two DNA strands are perfectly complementary, but with a 3’-overhang of the fluorophore strand. These unpaired nucleotides act as a toehold, which is utilized by a detached cleaved fragment (coming from a self-cleaving hammerhead ribozyme) as the starting point for a strand displacement reaction. This reaction causes the separation of the fluorophore strand from the quencher strand, culminating in fluorescence, detectable in a plate reader. Notably, the emitted fluorescence isproportionalto the amount of detached cleaved-off RNAs, displacing the DNA quencher strand. This method can replace or complement radio-hazardous unstable32P as a method of measurement of the kinetics of ribozyme cleavage reactions; it also eliminates the need for polyacrylamide gels, for the same purpose. Critically, this method allows to distinguish between the total amount of cleaved ribozymes and the amount ofdetachedfragments, resulting from that cleavage reaction.
Towards new models of cancer care in Australia: lessons from Victoria's response to the COVID‐19 pandemic
Authors: Underhill Craig , Parente Phillip , McArthur Grant , Haydon Andrew , McLachlan Sue‐Anne , Wong Zee Wan , Segelov Eva ,   Victorian COVID‐19 Cancer Network
Published: September 2020

In response to the COVID‐19 pandemic, the Department of Health and Human Services Victoria (DHHS), the Monash Partners Comprehensive Cancer Consortium (MPCCC) and Victorian Comprehensive Cancer Centre (VCCC) pooled their combined infrastructure to establish the Victorian COVID‐19 Cancer Network (VCCN) backed by a Taskforce of expert members. In a few short months, this state‐wide clinical network implemented a number of new models of care including clinics to manage acutely presenting cancer patients away from emergency departments, chemotherapy in the home, telehealth models and addressing sustainability of clinical trials.
Association of optimal blood pressure with mortality in patients taking antihypertensive medications
Authors: Yun Dong‐Ho , Lee Hye‐Sun , Choi Won‐Jun , Chang Hyuk‐Jae , Son Da‐Hye , Lee Ji‐Won
Published: September 2020

We investigated the relationship between blood pressure (BP) and mortality in patients taking antihypertensive medications in the Korean using data from the 2007‐2015 Korean National Health and Nutrition Examination Surveys. A total of 6601 patients aged 30‐74 years were included. Systolic BP (SBP) and diastolic BP (DBP) were both divided into four groups as follows: SBP < 120, 120 ≤ SBP ≤ 129 130 ≤ SBP ≤ 139, and SBP ≥ 140; DBP < 70, 70 ≤ DBP ≤ 79, 80 ≤ DBP ≤ 89, and DBP ≥ 90. The survival rates and hazard ratios were evaluated using Kaplan‐Meier curves and multivariable Cox regression analyses. To evaluate the predictability of all‐cause mortality according to SBP and/or DBP, we calculated Harrell's concordance‐index. The lowest DBP group had a high risk of mortality regardless of the SBP status. The group with DBP < 70 mm Hg and SBP ≥ 140 mm Hg showed the highest mortality. The discriminatory ability calculated using Harrell's C‐indexes was greater for the combination of SBP and DBP compared to DBP or SBP alone. These results suggest that it is more effective to simultaneously evaluate the effect of SBP and DBP to predict mortality; clinicians should manage DBP < 70 mm Hg when treating hypertensive patients.
Neuropilin‐1 is up‐regulated by cancer‐associated fibroblast‐secreted IL‐8 and associated with cell proliferation of gallbladder cancer
Authors: Chen Chen , Zhang Rui , Ma Li , Li Qi , Zhao Ya‐ling , Zhang Guan‐jun , Zhang Dong , Li Wen‐zhi , Cao Sheng , Wang Lin , Geng Zhi‐min
Published: September 2020

We previously demonstrated that cancer‐associated fibroblasts (CAFs) promoted the proliferation of gallbladder cancer (GBC) cells, but the mechanism is not clear. Neuropilin‐1 (NRP‐1) plays an important role in various malignancies as transmembrane glycoprotein. Our goal was to reveal the relationship between CAFs and NRP‐1 and their potential functions in GBC. In this study, we found NRP‐1 was overexpressed in GBC tissue, associated with poor survival and was up‐regulated by CAFs. The cytokine array cluster analysis revealed IL‐8 secreted by CAFs facilitated the up‐regulation of NRP‐1 in tumour cells. NRP‐1 knockdown suppressed tumour growth in vivo. Gene expression microarray analysis showed 581 differentially regulated genes under NRP‐1 knockdown conditions. Ingenuity pathway analysis demonstrated that NRP‐1 knockdown may inhibit tumour progression by affecting cell proliferation. We then confirmed that NRP‐1 knockdown in NOZ and GBC‐SD cells significantly inhibited cell proliferation. Additionally, the IL‐8 mediated MDM2 and CCNA2 expression were affected by NRP‐1 knockdown. Our findings suggested that NRP‐1 was up‐regulated by CAF‐secreted IL‐8, which subsequently promoted GBC cell proliferation, and these molecules may serve as useful prognostic biomarkers and therapeutic targets for GBC.
GLYCEROLYSIS USING KF/CAO-MGO CATALYST: OPTIMISATION AND REACTION KINETICS
Authors: Buchori Luqman , Djaeni Mohammad , Ratnawati R. , Retnowati Diah Susetyo , Hadiyanto H. , Anggoro Didi Dwi
Published: September 2020

Monoglycerides can be produced through glycerolysis using a heterogeneous catalyst. The purpose of this study is to analyse the optimum conditions for the production of monoglycerides from glycerol and cooking oil using KF/CaO-MgO base catalysts and to investigate the kinetics of the monoglyceride glycerolysis reaction. The response surface method (RSM) was used to determine the favourable conditions by varying the catalyst amount (X1) between 0.1, 0.2 and 0.3% (w/w); the reaction temperature (X2) between 210, 220 and 230°C and reaction time (X3) between 2, 3 and 4 hours. Gas chromatography-mass spectrometry (GC-MS) was used to determine the monoglycerides, while catalysts were characterised by X-ray diffraction (XRD) and the Brunauer-Emmett-Teller method (BET). The results showed that, among the three factors examined, temperature shows the most control over this glycerolysis reaction. The most favourable conditions are X1 = 0.19% (w/w), X2 = 208.37°C and X3 = 3.20 hours, which provide a monoglyceride yield of 41.58%. The constants for the reaction kinetics of the monoglyceride formation, k1 and k2 are 1.04189 and 0.88965 hour-1, respectively.
Characterization of water-based liquid scintillator for Cherenkov and scintillation separation
Authors: Caravaca J. , Land B. J. , Yeh M. , Orebi Gann G. D.
Published: September 2020

This paper presents measurements of the scintillation light yield and time profile for a number of concentrations of water-based liquid scintillator, formulated from linear alkylbenzene (LAB) and 2,5-diphenyloxazole (PPO). We find that the scintillation light yield is linear with the concentration of liquid scintillator in water between 1 and 10% with a slope of $$127.9\pm 17.0$$

127.9
±
17.0

ph/MeV/concentration and an intercept value of $$108.3\pm 51.0$$

108.3
±
51.0

ph/MeV, the latter being illustrative of non-linearities with concentration at values less than 1%. This is larger than expected from a simple extrapolation of the pure liquid scintillator light yield. The measured time profiles are consistently faster than that of pure liquid scintillator, with rise times less than 250 ps and prompt decay constants in the range of 2.1–2.85 ns. Additionally, the separation between Cherenkov and scintillation light is quantified using cosmic muons in the CHESS experiment for each formulation, demonstrating an improvement in separation at the centimeter scale. Finally, we briefly discuss the prospects for large-scale detectors.
Chemerin enhances the adhesion and migration of human endothelial progenitor cells and increases lipid accumulation in mice with atherosclerosis
Authors: Jia Jue , Yu Fan , Xiong Yuyun , Wei Weiping , Ma Hong , Nisi Fulvio , Song Xu , Yang Ling , Wang Dong , Yuan Guoyue , Zhou Hongwen
Published: September 2020

Background

The role of adipokines in the development of atherosclerosis (AS) has received increasing attention in recent years. This study aimed to explore the effects of chemerin on the functions of human endothelial progenitor cells (EPCs) and to investigate its role in lipid accumulation in ApoE-knockout (ApoE−/−) mice.

Methods

EPCs were cultured and treated with chemerin together with the specific p38 mitogen-activated protein kinase (MAPK) inhibitor SB 203580 in a time- and dose-dependent manner. Changes in migration, adhesion, proliferation and the apoptosis rate of EPCs were detected. ApoE−/− mice with high-fat diet-induced AS were treated with chemerin with or without SB 203580. Weights were recorded, lipid indicators were detected, and tissues sections were stained.

Results

The data showed that chemerin enhanced the adhesion and migration abilities of EPCs, and reduced the apoptosis ratio and that this effect might be mediated through the p38 MAPK pathway. Additionally, chemerin increased the instability of plaques. Compared with the control group and the inhibitor group, ApoE−/− mice treated with chemerin protein had more serious arterial stenosis, higher lipid contents in plaques and decreased collagen. Lipid accumulation in the liver and kidney and inflammation in the hepatic portal area were enhanced by treatment with chemerin, and the size of adipocytes also increased after chemerin treatment. In conclusion, chemerin can enhance the adhesion and migration abilities of human EPCs and reduce the apoptosis ratio. In animals, chemerin can increase lipid accumulation in atherosclerotic plaques and exacerbate plaques instability. At the same time, chemerin can cause abnormal lipid accumulation in the livers and kidneys of model animals. After specifically blocking the p38 MAPK pathway, the effect of chemerin was reduced.

Conclusions

In conclusion, this study showed that chemerin enhances the adhesion and migration abilities of EPCs and increases the instability of plaques and abnormal lipid accumulation in ApoE−/− mice. Furthermore, these effects might be mediated through the p38 MAPK pathway.
Haplotype threading: accurate polyploid phasing from long reads
Authors: Schrinner Sven D. , Mari Rebecca Serra , Ebler Jana , Rautiainen Mikko , Seillier Lancelot , Reimer Julia J. , Usadel Björn , Marschall Tobias , Klau Gunnar W.
Published: September 2020

Resolving genomes at haplotype level is crucial for understanding the evolutionary history of polyploid species and for designing advanced breeding strategies. Polyploid phasing still presents considerable challenges, especially in regions of collapsing haplotypes.We present WhatsHap polyphase, a novel two-stage approach that addresses these challenges by (i) clustering reads and (ii) threading the haplotypes through the clusters. Our method outperforms the state-of-the-art in terms of phasing quality. Using a real tetraploid potato dataset, we demonstrate how to assemble local genomic regions of interest at the haplotype level. Our algorithm is implemented as part of the widely used open source tool WhatsHap.
Joint inversion of full-waveform ground-penetrating radar and electrical resistivity data — Part 2: Enhancing low frequencies with the envelope transform and cross gradients
Authors: Domenzain Diego , Bradford John , Mead Jodi
Published: September 2020

Recovering material properties of the subsurface using ground-penetrating radar (GPR) data of finite bandwidth with missing low frequencies and in the presence of strong attenuation is a challenging problem. We have adopted three nonlinear inverse methods for recovering electrical conductivity and permittivity of the subsurface by joining GPR multioffset and electrical resistivity (ER) data acquired at the surface. All of the methods use ER data to constrain the low spatial frequency of the conductivity solution. The first method uses the envelope of the GPR data to exploit low-frequency content in full-waveform inversion and does not assume structural similarities of the material properties. The second method uses cross gradients to manage weak amplitudes in the GPR data by assuming structural similarities between permittivity and conductivity. The third method uses the envelope of the GPR data and the cross gradient of the model parameters. By joining ER and GPR data, exploiting low-frequency content in the GPR data, and assuming structural similarities between the electrical permittivity and conductivity, we are able to recover subsurface parameters in regions where the GPR data have a signal-to-noise ratio close to one.
Fluvial architecture and sequence stratigraphy of the Burro Canyon Formation, southwestern Piceance Basin, Colorado
Authors: Tellez Rodriguez Jerson J. , Pranter Matthew J. , Cole Rex
Published: September 2020

The Lower Cretaceous Burro Canyon Formation in the southwestern Piceance Basin, Colorado, is composed of deposits that represent a braided fluvial system with high net to gross that transitions stratigraphically upward into a low net-to-gross, low-sinuosity, meandering fluvial system. The fluvial deposits are composed of multiple upward-fining, conglomeratic-to-sandstone successions forming bars and bar sets that exhibit inclined heterolithic strata that we have interpreted to have formed by oblique and downstream accretion. We used well-exposed outcrops, detailed measured sections, and unmanned aerial system-based imagery to describe the fluvial architecture of the Late Cretaceous formation using a hierarchical approach. We described the Burro Canyon Formation as comprising sandstone-rich amalgamated channel complexes (ACC) overlain by non- to semiamalgamated channel complexes. The lower interval of the formation is composed of ACC that contain channel-fill elements with cross-stratification and numerous truncated contacts. These stacked channel-fill elements exhibit an apparent width range of 137–1300 ft (40–420 m) and a thickness range of 5–60 ft (1.5–18 m). The upper interval of the Burro Canyon Formation comprises mudstone-prone intervals of the nonamalgamated channel complex with isolated channel-fill elements interbedded with floodplain mudstones that represent a period of relatively high base level. Associate channel fill elements range in apparent width from 200 to 1000 ft (60 to 300 m) and thickness from 20 to 30 ft (6 to 18 m). The characteristics and spatial distribution of architectural elements of the Burro Canyon Formation correspond to one depositional sequence. The erosional basal surface of the formation, as well as lateral changes in thickness and net to gross, suggest that the Burro Canyon Formation within this study area was deposited as an incised valley fill. Fluvial deposits of the Burro Canyon Formation serve as outcrop analogs for subsurface interpretations in similar reservoirs.
Abemaciclib Combined With Endocrine Therapy for the Adjuvant Treatment of HR+, HER2−, Node-Positive, High-Risk, Early Breast Cancer (monarchE)
Authors: Johnston Stephen R. D. , Harbeck Nadia , Hegg Roberto , Toi Masakazu , Martin Miguel , Shao Zhi Min , Zhang Qing Yuan , Martinez Rodriguez Jorge Luis , Campone Mario , Hamilton Erika , Sohn Joohyuk , Guarneri Valentina , Okada Morihito , Boyle Frances , Neven Patrick , Cortés Javier , Huober Jens , Wardley Andrew , Tolaney Sara M. , Cicin Irfan , Smith Ian C. , Frenzel Martin , Headley Desirée , Wei Ran , San Antonio Belen , Hulstijn Maarten , Cox Joanne , O’Shaughnessy Joyce , Rastogi Priya ,   on behalf of the monarchE Committee Members and Investigators
Published: September 2020

PURPOSE

Many patients with HR+, HER2− early breast cancer (EBC) will not experience recurrence or have distant recurrence with currently available standard therapies. However, up to 30% of patients with high-risk clinical and/or pathologic features may experience distant recurrence, many in the first few years. Superior treatment options are needed to prevent early recurrence and development of metastases for this group of patients. Abemaciclib is an oral, continuously dosed, CDK4/6 inhibitor approved for HR+, HER2− advanced breast cancer (ABC). Efficacy and safety of abemaciclib in ABC supported evaluation in the adjuvant setting.

METHODS

This open-label, phase III study included patients with HR+, HER2−, high-risk EBC, who had surgery and, as indicated, radiotherapy and/or adjuvant/neoadjuvant chemotherapy. Patients with four or more positive nodes, or one to three nodes and either tumor size ≥ 5 cm, histologic grade 3, or central Ki-67 ≥ 20%, were eligible and randomly assigned (1:1) to standard-of-care adjuvant endocrine therapy (ET) with or without abemaciclib (150 mg twice daily for 2 years). The primary end point was invasive disease-free survival (IDFS), and secondary end points included distant relapse–free survival, overall survival, and safety.

RESULTS

At a preplanned efficacy interim analysis, among 5,637 randomly assigned patients, 323 IDFS events were observed in the intent-to-treat population. Abemaciclib plus ET demonstrated superior IDFS versus ET alone ( P = .01; hazard ratio, 0.75; 95% CI, 0.60 to 0.93), with 2-year IDFS rates of 92.2% versus 88.7%, respectively. Safety data were consistent with the known safety profile of abemaciclib.

CONCLUSION

Abemaciclib when combined with ET is the first CDK4/6 inhibitor to demonstrate a significant improvement in IDFS in patients with HR+, HER2− node-positive EBC at high risk of early recurrence.
The Effect of Problem Based Learning on EFL Students’ Critical Thinking Skill and Learning Outcome
Authors: Bashith Abdul , Amin Saiful
Published: September 2020

This research aims to examine the effect of Problem Based Learning (PBL) model to students’ critical thinking skill and learning outcome. It was conducted on the 11th graders of social science program at SMAN 6 Malang. The research material was the problems of demography. Research method was quasi experiment with non equivalent control group design. The data analysis used t-test technique. The research result showed that PBL learning model affected students’ critical thinking skill and learning outcome in SMAN 6 Malang. The average gain score of experimental class is 33.10, higher than control class, which is 16.24. The result of t-test analysis is 0.000 smaller than the significance of 0.05. It is suggested that PBL becomes one of aalternative teaching models that could be implemented to enhance students critical thingking skill.
The Effectiveness of Islamic Education Learning with Creative Worksheets through the Application of Quipper with Facebook Account
Authors: Das St. Wardah Hanafie , Halik Abdul , Herlin Besse Tuti
Published: September 2020

This study aims to determine the significance differences by those who are taught using Quipper through a facebook account in assigning creative worksheets and those who are not taught using Quipper in the field of Islamic education studies. This research method is an experiment with Quasi Nonequivalent control group design. The population was 70 people and the sample was divided into experiment class and control class with a total of 35 people each. The research instrument was the Observation Sheet, Student Learning Outcomes Test in the form of worksheets, questionnaires, study documents, and triangulation. Quantitative data analysis with descriptive and inferential non-parametric statistical techniques Mann Whitney U-Test test. Data analysis was assisted by SPSS application version 24. The results of the study were the use of Quipper School through a Facebook account in assigning creative worksheets to improve the effectiveness of Islamic education learning in SMK Negeri 1 Sengkang meeting the KKM, and there were significant differences between use and not use Quipper School through facebook account in assigning creative worksheets, and in the mann-whitney test, it is known the value of Asymp. Sig. (2- tailed) of 0,000 is smaller than probability value of 0.05 then the hypothesis H0 is rejected H1 is accepted. The next important study is the development of Quipper School media through a Facebook account on strengthening psychomotor competence in the field of Islamic education studies.
Availability analysis of an offshore oil and gas production system subjected to age-based preventive maintenance by Petri Nets
Authors: Lotovskyi Eduard , Teixeira Angelo , Soares Guedes Carlos
Published: September 2020

The main objective of this paper is to model an offshore oil production system subjected to
age-based preventive maintenance strategies by Petri Nets and to evaluate its availability by
Monte Carlo Simulation. The oil processing and the separation equipment with their reliability and maintainability characteristics, the corrective and preventive maintenance policies and the operational dependencies that lead to the reconfiguration of the system after the
failure are implemented. A special attention is given to the effect of age-based perfect and
imperfect preventive maintenance strategies on the system availability. The maintenance
actions consider the components’ age thresholds and an age reduction ratio. Moreover, the
variation of the oil and gas flows from the well over the years is accounted by the model. As
case study, an offshore production installation that operates in a Brazilian oilfield is adopted.
An elasticity analysis on the model parameters is conducted to assess influence of the maintenance policy on the system availability and on the oil production.