bluuebunny/crossref_metadata_2025_split huggingface dataset:
A functional genomic screen in Saccharomyces cerevisiae reveals divergent mechanisms of resistance to different alkylphosphocholine chemotherapeutic agents
Authors: Garcia Jaquelin M , Schwabe Michael J , Voelker Dennis R , Riekhof Wayne R 
Published: August 2021

Abstract
The alkylphosphocholine (APC) class of antineoplastic and antiprotozoal drugs, such as edelfosine and miltefosine, are structural mimics of lyso-phosphatidylcholine (lyso-PC), and are inhibitory to the yeast Saccharomyces cerevisiae at low micromolar concentrations. Cytotoxic effects related to inhibition of phospholipid synthesis, induction of an unfolded protein response, inhibition of oxidative phosphorylation, and disruption of lipid rafts have been attributed to members of this drug class, however, the molecular mechanisms of action of these drugs remain incompletely understood. Cytostatic and cytotoxic effects of the APCs exhibit variability with regard to chemical structure, leading to differences in effectiveness against different organisms or cell types. We now report the comprehensive identification of S. cerevisiae titratable-essential gene and haploid nonessential gene deletion mutants that are resistant to the APC drug miltefosine (hexadecyl-O-phosphocholine). Fifty-eight strains out of ∼5600 tested displayed robust and reproducible resistance to miltefosine. This gene set was heavily enriched in functions associated with vesicular transport steps, especially those involving endocytosis and retrograde transport of endosome derived vesicles to the Golgi or vacuole, suggesting a role for these trafficking pathways in transport of miltefosine to potential sites of action in the endoplasmic reticulum and mitochondrion. In addition, we identified mutants with defects in phosphatidylinositol-4-phosphate synthesis (TetO::STT4) and hydrolysis (sac1Δ), an oxysterol binding protein homolog (osh2Δ), a number of ER-resident proteins, and multiple components of the eisosome. These findings suggest that ER-plasma membrane contact sites and retrograde vesicle transport are involved in the interorganelle transport of lyso-PtdCho and related lyso-phospholipid-like analogs to their intracellular sites of cytotoxic activity.
Modeling in yeast how rDNA introns slow growth and increase desiccation tolerance in lichens
Authors: Armaleo Daniele , Chiou Lilly 
Published: August 2021

Abstract
We connect ribosome biogenesis to desiccation tolerance in lichens, widespread symbioses between specialized fungi (mycobionts) and unicellular phototrophs. We test whether the introns present in the nuclear ribosomal DNA of lichen mycobionts contribute to their anhydrobiosis. Self-splicing introns are found in the rDNA of several eukaryotic microorganisms, but most introns populating lichen rDNA are unable to self-splice, being either catalytically impaired group I introns, or spliceosomal introns ectopically present in rDNA. Although the mycobiont’s splicing machinery removes all introns from rRNA, Northern analysis indicates delayed post-transcriptional removal during rRNA processing, suggesting interference with ribosome assembly. To study the effects of lichen introns in a model system, we used CRISPR to introduce a spliceosomal rDNA intron from the lichen fungus Cladonia grayi into all nuclear rDNA copies of Saccharomyces cerevisiae, which lacks rDNA introns. Three intron-bearing yeast mutants were constructed with the intron inserted either in the 18S rRNA genes, the 25S rRNA genes, or in both. The mutants removed the introns correctly but had half the rDNA genes of the wildtype, grew 4.4–6 times slower, and were 40–1700 times more desiccation tolerant depending on intron position and number. Intracellular trehalose, a disaccharide implicated in desiccation tolerance, was detected at low concentration. Our data suggest that the interference of the splicing machinery with ribosome assembly leads to fewer ribosomes and proteins and to slow growth and increased desiccation tolerance in the yeast mutants. The relevance of these findings for slow growth and desiccation tolerance in lichens is discussed.
Development of a Predictive Score for Mortality at 3 and 12 Months After Discharge From an Acute Geriatric Unit as a Trigger for Advanced Care Planning
Authors: Deschasse Guillaume , Bloch Frédéric , Drumez Elodie , Charpentier Anne , Visade Fabien , Delecluse Celine , Loggia Gilles , Lescure Pascale , Attier-Żmudka Jadwiga , Bloch Jennifer , Gaxatte Cedric , Van Den Berghe William’s , Puisieux François , Beuscart Jean-Baptiste 
Published: August 2021

Abstract

Background
There is a need for a mortality score that can be used to trigger advanced care planning among older patients discharged from acute geriatric units (AGUs).

Objective
We developed a prognostic score for 3- and 12-month mortality after discharge from an AGU, based on a comprehensive geriatric assessment, in-hospital events, and the exclusion of patients already receiving palliative care.

Methods
Devenir Après la Médecine Aigue Gériatrique (DAMAGE) is a French multicenter, prospective, cohort study. The broad inclusion criteria ensured that the cohort is representative of patients treated in an AGU. The DAMAGE participants underwent a comprehensive geriatric assessment, a daily clinical checkup, and follow-up visits 3 and 12 months after discharge. Multivariable logistic regression models were used to develop a prognostic score for the derivation and validation subsets.

Results
A total of 3 509 patients were assessed and 3 112 were included. The patient population was very old and frail or dependant, with a high proportion of deaths at 3 months (n = 455, 14.8%) and at 12 months (n = 1 014, 33%). The score predicted an individual risk of mortality ranging from 1% to 80% at 3 months and between 5% and 93% at 12 months, with an area under the receiving operator characteristic curve in the validation cohort of 0.728 at 3 months and 0.733 at 12 months.

Conclusions
Our score predicted a broad range of risks of death after discharge from the AGU. Having this information at the time of hospital discharge might trigger a discussion on advanced care planning and end-of-life care with very old, frail patients.
Clinical Trials Registration Number: NCT02949635
Sensitivity analysis of the frozen soil nonlinear latent heat and its precise transformation method
Authors: Chen Zhixiang , Guo Xiaoxia , Shao Longtan , Li Shunqun , Gao Lingxia 
Published: August 2021

SUMMARY
Latent heat of soil water phase transition is an important parameter affecting the prediction of the temperature field in a frozen soil. With the nonlinear change of unfrozen water content in freezing soil, the latent heat appears nonlinearly in a frozen soil. To evaluate the influence of the estimation of phase quantity and phase change interval on the formation of the temperature field in a frozen soil, the thermal parameters at different temperatures are measured, and a soil freezing model test is carried out. Meanwhile, based on the evolutionary trend of the unfrozen water content, a precise method of transforming the latent heat of phase change into specific heat and a segment processing method of latent heat in a frozen soil are proposed. Also, these methods are used in the ABAQUS to simulate the temperature of the soil freezing model. The sensitivity of the estimation of phase quantity and phase change interval on the formation of the temperature field in a frozen soil is analysed based on the numerical calculation values and model test values. The results show that the estimation accuracy of phase change interval greatly affects the prediction accuracy of the temperature field in the warm temperature stage, and the method of transforming latent heat into apparent specific heat can improve the prediction accuracy of the temperature field.
Efficient numerical Bloch solutions for multipulse surface NMR
Authors: Griffiths Matthew P , Grombacher Denys J , Larsen Jakob Juul 
Published: August 2021

SUMMARY
Simplified solutions of the Bloch equation can lead to inaccurate estimates of hydrogeological parameters from surface nuclear magnetic resonance measurements. Even for single pulse measurements, using simplified forward models is common practice because of the computational intensity of obtaining the full-Bloch solution. These challenges are exacerbated for multipulse sequences. We show parallelizing the full-Bloch solver on a Graphics Processing Unit reduces the solve time by three orders of magnitude. Further optimizations by numerical, analytical and hybrid solutions yield an additional 3× speed up. We simulate the full-Bloch physics for free-induction decay, spin-echo and pseudo-saturation recovery excitation schemes for an unprecedented range of physical scenarios. We explore the time-dependence and relaxation time sensitivity in these solution spaces. Characterizing the solution spaces with polynomials of the relaxation times, the solutions can be rapidly reproduced; a technique known as fast-mapping. By fitting these higher dimensional solution ensembles with polynomials, the original fast-mapping technique is extended to include T1 at arbitrary times. Accuracy of the 7th order polynomial is such that a minimum 96 per cent of the models are within a ±3 per cent relative error. This permits the rapid reproduction of full-Bloch solutions with a matrix multiplication and opens up surface NMR to time-series based inversion of single and multipulse data.
The Impact of NAFLD on Hospitalization Outcomes in Patients With Inflammatory Bowel Diseases: Nationwide Analysis
Authors: Noorian Shaya , Jeon Yejoo , Nguyen Minh T , Sauk Jenny , Limketkai Berkeley N 
Published: August 2021

Abstract

Background
Nonalcoholic fatty liver disease (NAFLD) is highly prevalent in patients with inflammatory bowel diseases (IBD). Yet, the impact of NAFLD on outcomes, along with the contribution of nonmetabolic factors to NAFLD development, is unclear. To investigate these topics, we conducted a nationwide study examining the impact of NAFLD on hospitalization outcomes in IBD patients after adjusting for metabolic factors.

Methods
Patients with IBD-related hospitalizations were identified using the Nationwide Readmissions Database from 2016 to 2018. Inflammatory bowel disease patients with and without NAFLD were matched based on IBD type, age, sex, metabolic syndrome, and diabetes mellitus. Primary outcomes were IBD-related readmission, IBD-related surgery, and death. Secondary outcomes were length of stay (LOS) and cost of care (COC). The primary multivariable model adjusted for obesity, dyslipidemia, Charlson-Deyo comorbidity index, hospital characteristics, payer, patient income, and elective status of admissions.

Results
Nonalcoholic fatty liver disease was associated with a higher risk of IBD-related readmission (adjusted hazard ratio, 1.90; P &lt; .01) and death (adjusted hazard ratio, 2.73; P &lt; .01), 0.71-day longer LOS (P &lt; .01), and $7312 higher COC (P &lt; .01) in those with Crohn’s disease. Nonalcoholic fatty liver disease was also associated with a higher risk of IBD-related readmission (adjusted hazard ratio, 1.65; P &lt; .01), 0.64-day longer LOS (P &lt; .01), and $9392 (P &lt; .01) higher COC, but there was no difference in death in those with UC. No differences in risk of IBD-related surgery were observed.

Conclusions
Nonalcoholic fatty liver disease is associated with worse hospitalization outcomes in IBD patients after adjusting for metabolic factors. These data suggest nonmetabolic factors may be implicated in the pathogenesis of NAFLD in IBD patients and may contribute to worsened clinical outcomes.
ISDS Reform: The Long View
Authors: Alvarez José E 
Published: August 2021

Abstract
This lecture surveys the criticisms directed at international investment agreements (IIAs) and their reliance on investor-State dispute settlement (ISDS), as well as the leading reform venues that have been addressing such criticisms: UNCTAD, ICSID, and UNCITRAL. It argues that despite these ambitious efforts, the international investment regime’s reliance on investor-State arbitration will not be wholly displaced by any of the alternatives under active discussion – from national courts to mediation to a Multilateral Investment Court. In the long run, current reform efforts are likely to produce an ever more complex regime, governed by more diverse substantive rules interpreted by more complex options for dispute resolution. The focus on reforming the ways investor-State disputes are resolved fails to respond to doubts about the need for IIAs, undermines aspirations to harmonize international investment law, and ignores dire needs for stimulating (and protecting) foreign capital flows to achieve the goals of the Sustainable Development Goals – from mitigating climate change to preventing the next pandemic.
Minimal Gap in the Spectrum of the Sierpiński Gasket
Authors: Alonso Ruiz Patricia 
Published: August 2021

Abstract
This paper studies the size of the minimal gap between any two consecutive eigenvalues in the Dirichlet and in the Neumann spectrum of the standard Laplace operator on the Sierpiński gasket. The main result shows the remarkable fact that this minimal gap is achieved and coincides with the spectral gap. The Dirichlet case is more challenging and requires some key observations in the behavior of the dynamical system that describes the spectrum.
Increasing Viscosity Helps Explain Locomotor Control in Swimming Polypterus senegalus
Authors: Lutek K , Standen E M 
Published: August 2021

Synopsis
Locomotion relies on the successful integration of sensory information to adjust brain commands and basic motor rhythms created by central pattern generators. It is not clearly understood how altering the sensory environment impacts control of locomotion. In an aquatic environment, mechanical sensory feedback to the animal can be readily altered by adjusting water viscosity. Computer modeling of fish swimming systems shows that, without sensory feedback, high viscosity systems dampen kinematic output despite similar motor control input. We recorded muscle activity and kinematics of six Polypterus senegalus in four different viscosities of water from 1 cP (normal water) to 40 cP. In high viscosity, P. senegalus exhibit increased body curvature, body wave speed, and body and pectoral fin frequency during swimming. These changes are the result of increased muscle activation intensity and maintain voluntary swimming speed. Unlike the sensory-deprived model, intact sensory feedback allows fish to adjust swimming motor control and kinematic output in high viscous water but maintain typical swimming coordination.
Termite Pest Identification Method Based on Deep Convolution Neural Networks
Authors: Huang Jia-Hsin , Liu Yu-Ting , Ni Hung Chih , Chen Bo-Ye , Huang Shih-Ying , Tsai Huai-Kuang , Li Hou-Feng 
Published: August 2021

Abstract
Several species of drywood termites, subterranean termites, and fungus-growing termites cause extensive economic losses annually worldwide. Because no universal method is available for controlling all termites, correct species identification is crucial for termite management. Despite deep neural network technologies’ promising performance in pest recognition, a method for automatic termite recognition remains lacking. To develop an automated deep learning classifier for termite image recognition suitable for mobile applications, we used smartphones to acquire 18,000 original images each of four termite pest species: Kalotermitidae: Cryptotermes domesticus (Haviland); Rhinotermitidae: Coptotermes formosanus Shiraki and Reticulitermes flaviceps (Oshima); and Termitidae: Odontotermes formosanus (Shiraki). Each original image included multiple individuals, and we applied five image segmentation techniques for capturing individual termites. We used 24,000 individual-termite images (4 species × 2 castes × 3 groups × 1,000 images) for model development and testing. We implemented a termite classification system by using a deep learning–based model, MobileNetV2. Our models achieved high accuracy scores of 0.947, 0.946, and 0.929 for identifying soldiers, workers, and both castes, respectively, which is not significantly different from human expert performance. We further applied image augmentation techniques, including geometrical transformations and intensity transformations, to individual-termite images. The results revealed that the same classification accuracy can be achieved by using 1,000 augmented images derived from only 200 individual-termite images, thus facilitating further model development on the basis of many fewer original images. Our image-based identification system can enable the selection of termite control tools for pest management professionals or homeowners.
Forgotten Conflicts: Producing Knowledge and Ignorance in Security Studies
Authors: Brenner David , Han Enze 
Published: August 2021

Abstract
Security studies privileges the study of civil wars in some contexts over others. The field's leading journals mostly publish studies of armed conflicts in Africa, Eastern Europe, and the Middle East. Armed conflicts in Asia receive comparatively little attention, despite their prevalence and protracted nature. Against the background of our own empirical archive—the decades-old but largely ignored civil war in Myanmar—we ask why some conflicts draw more scholarly interest than others and why this uneven attention matters. In doing so, we argue that the empirical selectivity bias in the study of civil war and armed conflict reflects (1) institutional entanglements between the field of security studies and Western foreign policy; and (2) sociological factors that shape the formation of scholarly subjectivities and pertain to methodological challenges. This uneven empirical landscape shapes our conceptual understanding of civil wars. In fact, prominent debates within leading security studies journals surrounding the nature of civil war and armed conflict are inseparable from the empirical contexts in which they emerged. Leveling such an uneven empirical landscape thus generates opportunities for discussing conflict, insecurity, and violence in a different light. In shedding light on this issue, we urge closer attention to questions of place, time, and power in the scholarly production of knowledge and ignorance.
Moving on from Dutch to English: Young Refugees Feeling Betrayed by the Dutch Language Integration Policy and Seeking for More Inclusive Environments
Authors: Pozzo Moos 
Published: August 2021

AbstractThis article explores the linguistic strategies of young refugees (ages 12–23) in the Netherlands. The study takes place within a societal context in which new migrants and refugees are increasingly pressured to learn Dutch as key to their integration, but English is becoming more and more dominant, and in which learning Dutch is not considered necessary for other newcomer groups such as exchange students and expats. It starts from a puzzling finding in participants’ use of languages within their personal networks (collected 2016–18): their decreasing use of Dutch and increasing use of English while integrating into Dutch society. Participants’ ‘network stories’ reveal that they shifted from Dutch to English to distance themselves from the identities ascribed to them by the Dutch dominant negative discourse and to imagine their futures and belonging in more inclusive environments.
A universal relation between the properties of supermassive black holes, galaxies, and dark matter haloes
Authors: Marasco A , Cresci G , Posti L , Fraternali F , Mannucci F , Marconi A , Belfiore F , Fall S M 
Published: August 2021

ABSTRACT
We study the relations between the mass of the central black hole (BH) MBH, the dark matter halo mass Mh, and the stellar-to-halo mass fraction f⋆∝M⋆/Mh in a sample of 55 nearby galaxies with dynamically measured $M_{\rm BH}\gt 10^6\, {\rm M}_\odot$ and $M_{\rm h}\gt 5\times 10^{11}\, {\rm M}_\odot$. The main improvement with respect to previous studies is that we consider both early- and late-type systems for which Mh is determined either from globular cluster dynamics or from spatially resolved rotation curves. Independently of their structural properties, galaxies in our sample build a well defined sequence in the MBH–Mh–f⋆ space. We find that: (i) Mh and MBH strongly correlate with each other and anticorrelate with f⋆; (ii) there is a break in the slope of the MBH–Mh relation at Mh of $10^{12}\, {\rm M}_\odot$, and in the f⋆–MBH relation at MBH of $\sim 10^7\!-\!10^8\, {\rm M}_\odot$; (iii) at a fixed MBH, galaxies with a larger f⋆ tend to occupy lighter haloes and to have later morphological types. We show that the observed trends can be reproduced by a simple equilibrium model in the ΛCDM framework where galaxies smoothly accrete dark and baryonic matter at a cosmological rate, having their stellar and BH build-up regulated both by the cooling of the available gas reservoir and by the negative feedback from star formation and active galactic nuclei (AGNs). Feature (ii) arises as the BH population transits from a rapidly accreting phase to a more gentle and self-regulated growth, while scatter in the AGN feedback efficiency can account for feature (iii).
Uncovering fossils of the distant Milky Way with UNIONS: NGC 5466 and its stellar stream
Authors: Jensen Jaclyn , Thomas Guillaume , McConnachie Alan W , Starkenburg Else , Malhan Khyati , Navarro Julio , Martin Nicolas , Famaey Benoit , Ibata Rodrigo , Chapman Scott , Cuillandre Jean-Charles , Gwyn Stephen 
Published: August 2021

ABSTRACT
We examine the spatial clustering of blue horizontal branch (BHB) stars from the u-band of the Canada–France Imaging Survey (CFIS, a component of the Ultraviolet Near-Infrared Optical Northern Survey, or UNIONS). All major groupings of stars are associated with previously known satellites, and among these is NGC 5466, a distant (16 kpc) globular cluster. NGC 5466 reportedly possesses a long stellar stream, although no individual members of the stream have previously been identified. Using both BHBs and more numerous red giant branch stars cross-matched to Gaia Data Release 2, we identify extended tidal tails from NGC 5466 that are both spatially and kinematically coherent. Interestingly, we find that this stream does not follow the same path as the previous detection at large distances from the cluster. We trace the stream across 31° of sky and show that it exhibits a very strong distance gradient in the range 10 &lt; Rhelio &lt; 30 kpc. We compare our observations to simple dynamical models of the stream and find that they are able to broadly reproduce the overall path and kinematics. The fact that NGC 5466 is so distant, traces a wide range of Galactic distances, has an identified progenitor, and appears to have recently had an interaction with the Galaxy’s disc makes it a unique test-case for dynamical modelling of the Milky Way.