bluuebunny/crossref_metadata_2025 huggingface dataset:
Developing a monitoring system for Cloud-based distributed data-centers
Authors: Elia Domenico , Vino Gioacchino , Donvito Giacinto , Antonacci Marica
Published: September 2019

Nowadays more and more datacenters cooperate each others to achieve a common and more complex goal. New advanced functionalities are required to support experts during recovery and managing activities, like anomaly detection and fault pattern recognition. The proposed solution provides an active support to problem solving for datacenter management teams by providing automatically the root-cause of detected anomalies. The project has been developed in Bari using the datacenter ReCaS as testbed. Big Data solutions have been selected to properly handle the complexity and size of the data. Features like open source, big community, horizontal scalability and high availability have been considered and tools belonging to the Hadoop ecosystem have been selected. The collected information is sent to a combination of Apache Flume and Apache Kafka, used as transport layer, in turn delivering data to databases and processing components. Apache Spark has been selected as analysis component. Different kind of databases have been considered in order to satisfy multiple requirements: Hadoop Distributed File System, Neo4j, InfluxDB and Elasticsearch. Grafana and Kibana are used to show data in a dedicated dashboards. The Root-cause analysis engine has been implemented using custom machine learning algorithms. Finally, results are forwarded to experts by email or Slack, using Riemann.
Establishment of new WLCG Tier Center using HTCondor-CE on UMD middleware
Authors: Ryu Geonmo , Noh Seo-Young
Published: September 2019

CREAM is a CE program used by many sites based on UMD middleware to handle grid computing jobs. CREAM can be combined with various local batch programs, but it did not work with the HTCondor batch program. Since KISTI has been using HTCondor for many years, we searched another CE program which can work with HTCondor to process grid computing tasks. We proposed HTCondor-CE as the CE program, but it was not smoothly compatible with the UMD middleware environment because the OSG developed the HTCondor-CE software. In 2017, we manually configured HTCondor-CE and deployed a new CMS Tier-2 Center using the HTCondor-CE and a local HT-Condor cluster in the UMD middleware environment. The center has passed a SAM test suite that confirms the CMS computing performance of the center.
Sharing server nodes for storage and computer
Authors: Smith David , Di Girolamo Alessandro , Glushkov Ivan , Jones Ben , Kiryanov Andrey , Lamanna Massimo , Mascetti Luca , McCance Gavin , Rousseau Herve , Schovancová Jaroslava , Schulz Markus , Tollefsen Havard , Valassi Andrea
Published: September 2019

Based on the observation of low average CPU utilisation of several hundred file storage servers in the EOS storage system at CERN, the Batch on EOS Extra Resources (BEER) project developed an approach to also utilise these resources for batch processing. Initial proof of concept tests showed little interference between batch and storage services on a node. Subsequently a model for production was developed and implemented. This has been deployed on part of the CERN EOS production service. The implementation and test results will be presented. The potential for additional resources at the CERN Tier-0 centre is of the order of ten thousand hardware threads in the near term, as well as being a step towards a hyper-converged infrastructure.
Notifications workflows using the CERN IT central messaging infrastructure
Authors: Toteva Zhechka , Lukic Darko , Cons Lionel
Published: September 2019

In the CERN IT agile infrastructure (AI), Puppet, the CERN IT central messaging infrastructure (MI) and the Roger application are the key constituents handling the configuration of the machines of the computer centre. The machine configuration at any given moment depends on its declared state in Roger and Puppet ensures the actual implementation of the desired configuration by running the Puppet agent on the machine at regular intervals, typically every 90 minutes. Sometimes it is preferable that the configuration change is propagated immediately to the targeted machine, ahead of the next scheduled Puppet agent run on this machine. The particular need of handling notifications in a highly scalable manner for a large scale infrastructure has been satisfied with the implementation of the CERNMegabus architecture, based on the ActiveMQ messaging system. The design and implementation of the CERN-Megabus architecture are introduced, followed by the implementation of the Roger notification workflow. The choice of ActiveMQ is analysed and the message flow between the Roger notification producer and the CASTOR, EOS, BATCH and Load Balancing consumers are presented. The employment of predefined consumer modules in order to speed up the on-boarding of new CERN-Megabus use cases is also described.
MONIT: Monitoring the CERN Data Centres and the WLCG Infrastructure
Authors: Aimar Alberto , Aguado Corman Asier , Andrade Pedro , Delgado Fernandez Javier , Garrido Bear Borja , Karavakis Edward , Marek Kulikowski Dominik , Magnoni Luca
Published: September 2019

The new unified monitoring architecture (MONIT) for the CERN Data Centres and for the WLCG Infrastructure is based on established open source technologies to collect, stream, store and access monitoring data. The previous solutions, based on in-house development and commercial software, have been replaced with widely- recognized technologies such as Collectd, Kafka, Spark, Elasticsearch, InfluxDB, Grafana and others. The monitoring infrastructure, fully based on CERN cloud resources, covers the whole workflow of the monitoring data: from collecting and validating metrics and logs to making them available for dashboards, reports and alarms. The deployment in production of this new DC and WLCG monitoring is well under way and this contribution provides a summary of the progress, hurdles met and lessons learned in using these open source technologies. It also focuses on the choices made to achieve the required levels of stability, scalability and performance of the MONIT monitoring service.
Next Generation Generative Neural Networks for HEP
Authors: Farrell Steven , Bhimji Wahid , Kurth Thorsten , Mustafa Mustafa , Bard Deborah , Lukic Zarija , Nachman Benjamin , Patton Harley
Published: September 2019

Initial studies have suggested generative adversarial networks (GANs) have promise as fast simulations within HEP. These studies, while promising, have been insufficiently precise and also, like GANs in general, suffer from stability issues.We apply GANs to to generate full particle physics events (not individual physics objects), explore conditioning of generated events based on physics theory parameters and evaluate the precision and generalization of the produced datasets. We apply this to SUSY mass parameter interpolation and pileup generation. We also discuss recent developments in convergence and representations that match the structure of the detector better than images.In addition we describe on-going work making use of large-scale distributed resources on the Cori supercomputer at NERSC, and developments to control distributed training via interactive jupyter notebook sessions. This will allow tackling high-resolution detector data; model selection and hyper-parameter tuning in a productive yet scalable deep learning environment.
Quantum Computing
Authors: Amundson James , Sexton-Kennedy Elizabeth
Published: September 2019

In recent years Quantum Computing has attracted a great deal of
attention in the scientific and technical communities. Interest in the field has expanded to include the popular press and various funding agencies. We discuss the origins of the idea of using quantum systems for computing. We then give an overview in recent developments in quantum hardware and software, as well as some potential applications for high energy physics.
Oral and skin manifestations of tuberous sclerosis complex
Authors: Jacinthe Lafont , Jean-Hughes Catherine , Mathilde Lejeune , Ugo Ordioni , Romain Lan , Fabrice Campana
Published: September 2019

Tuberous sclerosis complex is a genetic disease characterized by multisystemic hamartomas with variable and non-specific clinical manifestations. The disease is associated with mutations of genes encoding the proteins hamartin and tuberin. The hamartin/tuberin complex plays an anti-tumor function by inhibiting mammalian target of rapamycin. The diagnostic criteria for the disease were reviewed at a consensus conference in 2012. Evidence of mutations of tuberous sclerosis complex 1 or 2 genes has become a clinical and independent diagnostic criterion. Among the clinical criteria used, two oral criteria include the presence of three or more enamel pits and the presence of two or more oral fibromas. Several dermatological criteria are included within these criteria and are of interest in our specialty when these are localized at the cephalic extremity.
Oral manifestations of a sinus melanoma: case report and literature review
Authors: Le Donne Mélanie , Bodard Anne-Gaëlle , Lesage Candice , Fleury Bertrand
Published: September 2019

Introduction:Mucosal melanoma (MM) is a rare malignancy of the head and neck. Sinonasal melanomas are the most frequent, followed by oral melanomas.Observation:A 67-year-old patient with a known left sinus melanoma initially treated with immunotherapy was referred for consultation concerning mobile teeth. A pigmented lesion infiltrating the left maxillary arch in the molar area was detected. The malignancy had invaded the oral mucosa. Despite many proposed treatments (immunotherapy, chemotherapy, and radiotherapy), the patient showed metastatic progression, which resulted in death.Discussion:Sinus MMs are malignancies with poor prognosis because these are often diagnosed in the late stages of disease progression. As these tumors are rare, there is no treatment consensus and surgery remains the best option. Diagnosis of pigmented lesions of the oral mucosa is sometimes complicated because of various implied etiologies.Conclusion:This case report shows that sinus MMs can induce pigmentation in the oral mucosa. These are rare malignancies with poor prognosis, for which no treatment consensus exists to date.
Endothelial and Autonomic Dysfunction at Early Stages of Glucose Intolerance and in Metabolic Syndrome
Authors: Dimova Rumyana , Tankova Tsvetalina , Kirilov Georgi , Chakarova Nevena , Grozeva Greta , Dakovska Lilia
Published: September 2019

This study evaluated sE-selectin, Endothelin-1, and cardiovascular autonomic neuropathy (CAN) at early stages of glucose intolerance and in metabolic syndrome (MetS). A total of 87 subjects – 39 males, of mean age 45.7±11.6 years and mean BMI 31.4±6.6 kg/m2, divided according to glucose tolerance and the presence of MetS were enrolled. Glucose tolerance was studied during OGTT. Anthropometric indices, blood pressure, HbA1c, lipids, hsCRP, sE-selectin, Endothelin-1, and immunoreactive insulin were measured. Body composition was assessed by a bioimpedance method (InBody 720, BioSpace). Tissue AGEs accumulation was evaluated by skin autofluorescence (AGE-Reader, DiagnOpticsTM). CAN was assessed by ANX-3.0 technology. In the groups, according to glucose tolerance, the prevalence of CAN was 5.7% in normal glucose tolerance (NGT), 8.6% in prediabetes, and 23.5% in newly diagnosed type 2 diabetes (NDD). In the groups, according to the presence of MetS, the prevalence of CAN was 12.3% in those with MetS and 4.8% in those without MetS. Parasympathetic activity was diminished at rest (p=0.048, 0.015, respectively) in NDD as compared to prediabetes and NGT; and there was a numerically elevated heart rate at rest in NDD in comparison to NGT. There was a negative correlation between parasympathetic tone and waist circumference, BMI, and visceral and total fat. There was no difference in the measured endothelial function markers in the groups according to glucose tolerance and MetS. sE-selectin correlated with HOMA-IR (r=0.275, p=0.048). No association between Endothelin-1 levels and assessed metabolic parameters was observed. There is a high prevalence of CAN at early stages of glucose intolerance and in MetS, due to decreased parasympathetic activity. Slight elevation of glycemia and MetS probably do not affect endothelial function, since sE-selectin seems to be related to insulin resistance.
Brucella-Induced Ruptured Infrarenal Dissecting Abdominal Aortic Aneurysm
Authors: Ramachandran Nair Harishankar , Goura Prakash , Pitchai Shivanesan , Madathipat Unnikrishnan
Published: September 2019

Mycotic aneurysms, often saccular, accounting for approximately 2.5% of all abdominal aortic aneurysms, possess increased risk of rupture, uncontrolled sepsis, and protracted hospital stay and are associated with high morbidity and mortality. The authors report the case of a 49-year-old female with no known comorbidities who presented with free rupture of an infrarenal dissecting mycotic aneurysm and underwent emergent open repair successfully. The etiological agent, Brucella melitensis, a Gram-negative zoonotic coccobacillus, is rarely reported to cause mycotic aneurysm.
Association Between Features of Spontaneous Late Preterm Labor and Late Preterm Birth
Authors: Glover Angelica V. , Battarbee Ashley N. , Gyamfi-Bannerman Cynthia , Boggess Kim A. , Sandoval Grecio , Blackwell Sean C. , Tita Alan T. N. , Reddy Uma M. , Jain Lucky , Saade George R. , Rouse Dwight J. , Iams Jay D. , Clark Erin A. S. , Chien Edward K. , Peaceman Alan M. , Gibbs Ronald S. , Swamy Geeta K. , Norton Mary E. , Casey Brian M. , Caritis Steve N. , Tolosa Jorge E. , Sorokin Yoram , Manuck Tracy A. ,   for the Eunice Kennedy Shriver National Institute of Child Health Human Development Maternal-Fetal Medicine Units Network
Published: September 2019

Objective This study aimed to evaluate the association between clinical and examination features at admission and late preterm birth.

Study Design The present study is a secondary analysis of a randomized trial of singleton pregnancies at 340/7 to 365/7 weeks' gestation. We included women in spontaneous preterm labor with intact membranes and compared them by gestational age at delivery (preterm vs. term). We calculated a statistical cut-point optimizing the sensitivity and specificity of initial cervical dilation and effacement at predicting preterm birth and used multivariable regression to identify factors associated with late preterm delivery.

Results A total of 431 out of 732 (59%) women delivered preterm. Cervical dilation ≥ 4 cm was 60% sensitive and 68% specific for late preterm birth. Cervical effacement ≥ 75% was 59% sensitive and 65% specific for late preterm birth. Earlier gestational age at randomization, nulliparity, and fetal malpresentation were associated with late preterm birth. The final regression model including clinical and examination features significantly improved late preterm birth prediction (81% sensitivity, 48% specificity, area under the curve = 0.72, 95% confidence interval [CI]: 0.68–0.75, and p-value < 0.01).

Conclusion Four in 10 women in late-preterm labor subsequently delivered at term. Combination of examination and clinical features (including parity and gestational age) improved late-preterm birth prediction.
Does Prepregnancy Weight or Maternal BMI at Betamethasone Administration Impact Late Preterm Respiratory Morbidity?
Authors: Bicocca Matthew J. , Blackwell Sean C. , Sibai Baha M.
Published: September 2019

Objective We sought to determine if maternal prepregnancy body mass index (BMI) is a risk factor for neonatal respiratory morbidity and to determine if increasing BMI decreased the efficacy of betamethasone (BMZ).

Study Design This was a secondary analysis of the Antenatal Late Preterm Steroids trial, double-blind, randomized controlled trial involving 2,831 women between 340/7 and 365/7 weeks who received BMZ or a matching placebo. We compared the rate of neonatal respiratory morbidity among prepregnancy BMI classes in both the placebo and treatment groups. We also stratified the treatment effect by maternal BMI at the time of delivery.

Results A total of 2,822 women were identified with maternal weight recorded at delivery; 2,740 women also had self-reported prepregnancy weight available. When stratified by prepregnancy BMI class, there was no difference in neonatal respiratory morbidity in the BMZ or in placebo groups. When analyzed by BMI at delivery, there was no difference in the rate of neonatal respiratory morbidity, and BMI was not a predictor of treatment response (odds ratio = 1.00, 95% confidence interval = 0.99–1.02).

Conclusion Maternal prepregnancy BMI is not associated with late preterm neonatal respiratory morbidity. Maternal obesity does not decrease the efficacy of BMZ for preventing late preterm neonatal respiratory morbidity.
Risk Factors for Maternal Readmission with Sepsis
Authors: Foeller Megan E. , Sie Lillian , Foeller Timothy M. , Girsen Anna I. , Carmichael Suzan L. , Lyell Deirdre J. , Lee Henry C. , Gibbs Ronald S.
Published: September 2019

Objective Our primary objective was to identify risk factors for maternal readmission with sepsis. Our secondary objectives were to (1) assess diagnoses and infecting organisms at readmission and (2) compare early (<6 weeks) and late (6 weeks to 9 months postpartum) maternal readmission with sepsis.

Study Design We identified our cohort using linked hospital discharge data and birth certificates for California deliveries from 2008 to 2011. Consistent with the 2016 sepsis classification, we defined sepsis as septicemia plus acute organ dysfunction. We compared women with early or late readmission with sepsis to women without readmission with sepsis.

Results Among 1,880,264 women, 494 (0.03%) were readmitted with sepsis, 61% after 6 weeks. Risk factors for readmission with sepsis included preterm birth, hemorrhage, obesity, government-provided insurance, and primary cesarean. For both early and late sepsis readmissions, the most common diagnoses were urinary tract infection and pyelonephritis, and the most frequently identified infecting organism was gram-negative bacteria. Women with early compared with late readmission with sepsis shared similar obstetric characteristics.

Conclusion Maternal risk factors for both early and late readmission with sepsis included demographic characteristics, cesarean, hemorrhage, and preterm birth. Risks for sepsis after delivery persist beyond the traditional postpartum period of 6 weeks.
Trends in the Management Paradigms of Intracranial Meningioma
Authors: Aljuboori Zaid , Alhourani Ahmad , Woo Shiao , Hattab Eyas , Yusuf Mehran , Nelson Megan , Andaluz Norberto , Ding Dale , Savage Jesse , Williams Brian
Published: September 2019

Objective Intracranial meningiomas are the most common primary brain tumor. Treatment paradigms have evolved over time. There are limited number of population-based studies that examine this modern evolution. Here, we describe the trends of management of intracranial meningiomas using a national database.

Methods The data were obtained from the National Cancer Database for the years 2004 to 2015, the collected variables included: patients' age, gender, insurance type, income, comorbidity score, the tumor size and grade, and treatment modality (observation, surgery, radiotherapy, or combination therapy). We performed statistical analyses to detect association between unique variables and outcomes. In addition, we performed mortality analyses for various treatment modalities.

Results A total of 199,096 patients with a diagnosis of intracranial meningioma were included, the majority of patients were white females, mean age of 61 years, and half of the tumors were ≤ 3 cm. Observation was the most commonly used management modality followed by surgical resection, radiotherapy, and combination therapy. For the entire time period, there was an increased use of observation as a primary management method. Predictors of mortality included increased age, larger tumor size, higher tumor grade, treatment at a community hospital, and higher comorbidity scores.

Conclusion Population-based studies of intracranial meningiomas are uncommon; our study is one of the few reports that examine the changes in the modern management paradigms of meningioma in the United States over time. Additionally, we shed light on the factors that affected survival of patients with this condition.
Time-dependent methods in inverse scattering problems for the Hartree-Fock equation
Authors: Watanabe Michiyuki
Published: September 2019

The major purpose of this paper is to establish a reconstruction procedure of two-body interactions from scattering solutions for a Hartree-Fock equation. We give a uniqueness theorem and propose a new reconstruction procedure of the short-range and two-body interactions from a high-velocity limit of the scattering operator for the Hartree-Fock equation. Moreover, it will be found that the high-velocity limit of the scattering operator is equal to a small-amplitude limit of the scattering operator.
The impact of swift electrons on the segregation of Ni-Au nanoalloys
Authors: Knez Daniel , Schnedlitz Martin , Lasserus Maximilian , Hauser Andreas W. , Ernst Wolfgang E. , Hofer Ferdinand , Kothleitner Gerald
Published: September 2019

We report on the electron beam-induced segregation of alloyed Ni-Au clusters into a Ni and Au rich phase at temperatures above the miscibility gap of a binary system. The nanoparticles, with diameters less than 10 nm, are grown fully inert in superfluid helium droplets with a Ni-Au core-shell morphology. Upon heating, the clusters are alloyed and subsequently transformed to a Janus-type morphology under irradiation with swift electrons. The underlying mechanisms are studied experimentally via in situ scanning transmission electron microscopy and theoretically via atomistic simulation techniques under consideration of elastic electron interactions. We find that the segregation kinetics is highly temperature-dependent and attribute this behavior to diffusive relaxation processes. The presented results shed light on radiation induced phenomena using clusters as a model system and suggest new routes for the synthesis of structures in nonequilibrium configurations.
Velocity controlled pattern writing: An application of stochastic resonance
Authors: Roy Tanushree , Parmananda P.
Published: September 2019

In the present work, the concept of stochastic resonance is employed for pattern fabrication. In particular, the interplay of noise amplitudes and intrinsic system time scales is investigated. This interplay enabled us to obtain preordained patterns. Experiments were performed galvanostatically in a two electrode electrochemical cell onto a n-type Si substrate using a coherent wavelength laser source of 5 mW intensity. A focused laser beam was swept along the silicon substrate unidirectionally by moving the electrochemical cell at different velocities. By systematic tuning of the velocity, we have observed a unimodal variation in the contrast of the pattern. This indicates the occurrence of the stochastic resonance phenomena. Corresponding numerical simulations, performed on a spatial array of diffusively coupled FitzHugh-Nagumo oscillators in the presence of external noise, reveal good agreement with the experimental observations.
Time-resolved X-ray diffraction system for study of Pb(Zr, Ti)O3 films under a temporal electric field at BL15XU, SPring-8
Authors: Seo Okkyun , Kim Jaemyung , Song Chulho , Katsuya Yoshio , Shimada Yoshitomo , Yamada Tomoaki , Sakata Osami
Published: September 2019

We report on the use of a time-resolved X-ray diffraction system to study a piezoelectric material under a temporal electric field at the BL15XU NIMS beamline, at SPring-8 in Japan. By synchronizing focused X-rays onto a device under an applied electric field with a two-dimensional detector and measurements performed with respect to the synchrotron clock signal, we successfully observed shifts of the 222 Bragg peak of 750-nm-thick Pb(Zr, Ti)O3 films near time zero under a unipolar rectangular wave at 24 V. We expect that this system might be useful for understanding the piezoresponse, lattice dynamics, and domain switching dynamics of functional oxide thin films.
Three-dimensional simulation of a rising bubble in the presence of spherical obstacles by the immersed boundary–lattice Boltzmann method
Authors: Chen Guo-Qing , Huang Xiao , Zhang A-Man , Wang Shi-Ping , Li Tong
Published: September 2019

The dynamics of a bubble bypassing or passing between spherical obstacles, which is associated with many industrial applications, is investigated numerically. A gas–liquid–solid interaction model is established by combining the lattice Boltzmann method and the immersed boundary method. The deformation and the surface velocity of the bubble, as well as the streamlines of the flow field, are studied as the bubble bypasses a single spherical obstacle or passes between a pair of such obstacles. It is found that for the case of a single sphere, the rise velocity reaches a minimum value at the moment at which an annular bubble forms and the whole sphere is enveloped by the bubble. The initial distance between the bubble and the sphere, as well as the ratio of their sizes, has distinct influences on bubble shape and rise velocity. For a pair of spherical obstacles, the rise velocity of the bubble reaches a minimum value twice as the bubble rises between the obstacles. The distance between the two obstacles has a stronger influence on bubble motion than does their size, although when the two obstacles are of different sizes, the bubble will deviate toward the smaller one.
National cost savings from an ambulatory program for low-risk febrile neutropenia patients in Australia
Authors: Tew Michelle , Forster Daniel , Teh Benjamin W. , Dalziel Kim
Published: September 2019

Objective The management of low-risk febrile neutropenia (FN) patients through ambulatory programs has demonstrated comparative safety and effectiveness to in-patient strategies. However, there is limited evidence of benefits of changing practice, particularly on a national scale. The aim of this study was to estimate costs and benefits of the program over a 10-year time horizon. Methods A comparative cost analysis from a health system perspective was performed, comparing costs and length of stay (LOS) of patients enrolled in an ambulatory program to a historical cohort who did not receive the program. Generalised linear models were used for analysis and bootstrapped to account for uncertainty. National data of identified FN admissions were used to inform future projections, with varying proportions of low-risk patients and eligibility for the ambulatory program. Results The overall LOS for patients in ambulatory cohort was 1.9 days shorter (95% confidence interval (CI) 1.0–2.8 days), a 50% reduction in in-patient bed-days. Although patients in the ambulatory cohort incurred additional costs due to care received outside hospital (mean (± s.d.) A$828.03 ± 124.30), the mean total cost incurred remained substantially lower than that of the historical cohort (A$2979 lower; 95% CI A$772–5391). On a national scale, this could translate into A$62.7 million in costs averted and 41 347 bed-days saved over 10 years if the low-risk prediction rate and eligibility for ambulatory programs remained at currently observed rates. Conclusions The wider implementation of a safe and effective ambulatory program to manage low-risk FN patients can result in significant return-on-investment for the healthcare system by eliminating avoidable costs due to unnecessary lengthy hospital admissions. What is known about the topic? There is strong evidence demonstrating out-patient treatment of low-risk FN patients to be an effective and cost-effective strategy compared with continued in-patient hospitalisation. What does this paper add? This study demonstrates the sustainability of the ambulatory program in ensuring cost benefits and in-patient beds through real-life implementation data. It also provides evidence of the substantial cost and bed-days potentially averted when the cost savings and difference in LOS are estimated on a national scale over a 10-year time horizon. What are the implications for practitioners? The management of low-risk FN patients through ambulatory or out-patient programs is a safe and effective approach. There is strong evidence demonstrating the likely cost savings and considerable bed-days saved, which can be reallocated to meet other medical demands.
Organic based integrated nutrient management scheme enhances soil carbon storage in rainfed rice (Oryza sativa) cultivation
Authors: Saikia Parijat , Baruah Kushal Kumar , Sundar Bhattacharya Satya , Choudhury Chandrima
Published: September 2019

Soil organic carbon (C) management in agricultural fields can act improve soil health and productivity. However, reports on the C release pattern and the interactive effects of plant physiological parameters on soil C storage from subtropical regions of the world where rice is cultivated as a dominant food crop are inadequate. The interactions between plant metabolism, soil C storage, and organic-based nutrient management schemes have been little studied. Hence, a study was undertaken in rainfed winter rice to evaluate the effects of different levels of organics (crop residue (CR) and farmyard manure (FYM)) along with inorganic (NPK) inputs in an alluvial soil. The experiment was conducted in a typical humid subtropical climate in north-eastern India. The CR of the preceding rice crop (pre-monsoon) and cow dung based FYM were used as organic inputs for monsoon rice, which were applied in various combinations with inorganic fertilisers. We studied the influence of these selected nutrient management schemes on soil health attributes, C storage, and plant parameters. The highest gain in C storage (11.65%) was in soil under 80% NPK + CR (5 t ha–1) + FYM (10 t ha–1) treatment. Correspondingly, significant improvement (P < 0.05) in total C, dissolved organic C, and nitrogen availability in soil was evident under this treatment leading to augmentation of soil organic matter status and the net amount of sequestered C in soil after two years of rice cultivation. Such improvements resulted in greater flag leaf photosynthesis, biomass accumulation, and grain yield than the conventionally managed crops. Overall, this research showcases that organic-dominated nutrient management not only restored soil health but was also able to compensate 20% of the recommended NPK fertilisation without penalty on crop yield.
Building more accurate decision trees with the additive tree
Authors: Luna José Marcio , Gennatas Efstathios D. , Ungar Lyle H. , Eaton Eric , Diffenderfer Eric S. , Jensen Shane T. , Simone Charles B. , Friedman Jerome H. , Solberg Timothy D. , Valdes Gilmer
Published: September 2019

Significance

As machine learning applications expand to high-stakes areas such as criminal justice, finance, and medicine, legitimate concerns emerge about high-impact effects of individual mispredictions on people’s lives. As a result, there has been increasing interest in understanding general machine learning models to overcome possible serious risks. Current decision trees, such as Classification and Regression Trees (CART), have played a predominant role in fields such as medicine, due to their simplicity and intuitive interpretation. However, such trees suffer from intrinsic limitations in predictive power. We developed the additive tree, a theoretical approach to generate a more accurate and interpretable decision tree, which reveals connections between CART and gradient boosting. The additive tree exhibits superior predictive performance to CART, as validated on 83 classification tasks.
Atp6ap2
deletion causes extensive vacuolation that consumes the insulin content of pancreatic β cells
Authors: Binger Katrina J. , Neukam Martin , Tattikota Sudhir Gopal , Qadri Fatimunnisa , Puchkov Dmytro , Willmes Diana M. , Wurmsee Sabrina , Geisberger Sabrina , Dechend Ralf , Raile Klemens , Kurth Thomas , Nguyen Genevieve , Poy Matthew N. , Solimena Michele , Muller Dominik N. , Birkenfeld Andreas L.
Published: September 2019

Significance

Cells maintain several mechanisms to ensure their survival, including the removal of old or damaged proteins and organelles. This process must be balanced: too little turnover results in the accumulation of cellular “junk,” while excessive removal can deplete the cell and organism of key components. Here, we show that
Atp6ap2
in the pancreatic β cell is essential for insulin granule turnover, as its absence resulted in the accumulation of oversized cytosolic vacuoles which conceivably account for excessive granule degradation, and thereby leads to impaired insulin secretion and diabetes.
Identification of
C2CD4A
as a human diabetes susceptibility gene with a role in β cell insulin secretion
Authors: Kuo Taiyi , Kraakman Michael J. , Damle Manashree , Gill Richard , Lazar Mitchell A. , Accili Domenico
Published: September 2019

Fine mapping and validation of genes causing β cell failure from susceptibility loci identified in type 2 diabetes genome-wide association studies (GWAS) poses a significant challenge. The
VPS13C-C2CD4A-C2CD4B
locus on chromosome 15 confers diabetes susceptibility in every ethnic group studied to date. However, the causative gene is unknown. FoxO1 is involved in the pathogenesis of β cell dysfunction, but its link to human diabetes GWAS has not been explored. Here we generated a genome-wide map of FoxO1 superenhancers in chemically identified β cells using 2-photon live-cell imaging to monitor FoxO1 localization. When parsed against human superenhancers and GWAS-derived diabetes susceptibility alleles, this map revealed a conserved superenhancer in
C2CD4A
, a gene encoding a β cell/stomach-enriched nuclear protein of unknown function. Genetic ablation of C2cd4a in β cells of mice phenocopied the metabolic abnormalities of human carriers of
C2CD4A
-linked polymorphisms, resulting in impaired insulin secretion during glucose tolerance tests as well as hyperglycemic clamps. C2CD4A regulates glycolytic genes, and notably represses key β cell “disallowed” genes, such as
lactate dehydrogenase A
. We propose that
C2CD4A
is a transcriptional coregulator of the glycolytic pathway whose dysfunction accounts for the diabetes susceptibility associated with the chromosome 15 GWAS locus.
Nmnat restores neuronal integrity by neutralizing mutant Huntingtin aggregate-induced progressive toxicity
Authors: Zhu Yi , Li Chong , Tao Xianzun , Brazill Jennifer M. , Park Joun , Diaz-Perez Zoraida , Zhai R. Grace
Published: September 2019

Significance

Huntington’s disease (HD) is a dominantly inherited neurodegenerative disorder caused by expansion of CAG repeats in
huntingtin
(Htt). The mutant Htt protein containing expanded polyglutamine is prone to misfolding and aggregation; however, the cytotoxicity of mutant Htt aggregation remains elusive. Here, we describe the cytotoxicity of mutant Htt aggregates in distinct neuronal compartments, reveal the amyloid-like biochemical properties of aggregates that correlate with the severity of neurodegeneration, and demonstrate the robust neuroprotection of NMNAT, a conserved NAD
+
synthase, through reducing Htt aggregation and neutralizing the damaging adhesive property of aggregates. Importantly, induction of Nmnat postphenotypic onset neutralizes cytotoxicity and exerts immediate neuroprotection. Our study provides insights into the neuropathology of HD and implications of aggregate-neutralizing as a therapeutic strategy.
A higher-order configuration of the heterodimeric DOT1L–AF10 coiled-coil domains potentiates their leukemogenenic activity
Authors: Song Xiaosheng , Yang Liuliu , Wang Mingzhu , Gu Yue , Ye Buqing , Fan Zusen , Xu Rui-Ming , Yang Na
Published: September 2019

Chromosomal translocations of
MLL1
(Mixed Lineage Leukemia 1) yield oncogenic chimeric proteins containing the N-terminal portion of MLL1 fused with distinct partners. The MLL1–AF10 fusion causes leukemia through recruiting the H3K79 histone methyltransferase DOT1L via AF10’s octapeptide and leucine zipper (OM-LZ) motifs. Yet, the precise interaction sites in DOT1L, detailed interaction modes between AF10 and DOT1L, and the functional configuration of MLL1–AF10 in leukeomogenesis remain unknown. Through a combined approach of structural and functional analyses, we found that the LZ domain of AF10 interacts with the coiled-coil domains of DOT1L through a conserved binding mode and discovered that the C-terminal end of the LZ domain and the OM domain of AF10 mediate the formation of a DOT1L–AF10 octamer via tetramerization of the binary complex. We reveal that the oligomerization ability of the DOT1L–AF10 complex is essential for MLL1–AF10’s leukemogenic function. These findings provide insights into the molecular basis of pathogenesis by MLL1 rearrangements.
The circadian clock of CD8 T cells modulates their early response to vaccination and the rhythmicity of related signaling pathways
Authors: Nobis Chloé C. , Dubeau Laramée Geneviève , Kervezee Laura , Maurice De Sousa Dave , Labrecque Nathalie , Cermakian Nicolas
Published: September 2019

Circadian variations of various aspects of the immune system have been described. However, the circadian control of T cells has been relatively unexplored. Here, we investigated the role of circadian clocks in regulating CD8 T cell response to antigen presentation by dendritic cells (DCs). The in vivo CD8 T cell response following vaccination with DCs loaded with the OVA257–264peptide antigen (DC-OVA) leads to a higher expansion of OVA-specific T cells in response to vaccination done in the middle of the day, compared to other time points. This rhythm was dampened when DCs deficient for the essential clock geneBmal1were used and abolished in mice with a CD8 T cell-specificBmal1deletion. Thus, we assessed the circadian transcriptome of CD8 T cells and found an enrichment in the daytime of genes and pathways involved in T cell activation. Based on this, we investigated early T cell activation events. Three days postvaccination, we found higher T cell activation markers and related signaling pathways (including IRF4, mTOR, and AKT) after a vaccination done during the middle of the day compared to the middle of the night. Finally, the functional impact of the stronger daytime response was shown by a more efficient response to a bacterial challenge at this time of day. Altogether, these results suggest that the clock of CD8 T cells modulates the response to vaccination by shaping the transcriptional program of these cells and making them more prone to strong and efficient activation and proliferation according to the time of day.
Microbiome composition shapes rapid genomic adaptation ofDrosophila melanogaster
Authors: Rudman Seth M. , Greenblum Sharon , Hughes Rachel C. , Rajpurohit Subhash , Kiratli Ozan , Lowder Dallin B. , Lemmon Skyler G. , Petrov Dmitri A. , Chaston John M. , Schmidt Paul
Published: September 2019

Population genomic data has revealed patterns of genetic variation associated with adaptation in many taxa. Yet understanding the adaptive process that drives such patterns is challenging; it requires disentangling the ecological agents of selection, determining the relevant timescales over which evolution occurs, and elucidating the genetic architecture of adaptation. Doing so for the adaptation of hosts to their microbiome is of particular interest with growing recognition of the importance and complexity of host–microbe interactions. Here, we track the pace and genomic architecture of adaptation to an experimental microbiome manipulation in replicate populations ofDrosophila melanogasterin field mesocosms. Shifts in microbiome composition altered population dynamics and led to divergence between treatments in allele frequencies, with regions showing strong divergence found on all chromosomes. Moreover, at divergent loci previously associated with adaptation across natural populations, we found that the more common allele in fly populations experimentally enriched for a certain microbial group was also more common in natural populations with high relative abundance of that microbial group. These results suggest that microbiomes may be an agent of selection that shapes the pattern and process of adaptation and, more broadly, that variation in a single ecological factor within a complex environment can drive rapid, polygenic adaptation over short timescales.
The value of thoughts and prayers
Authors: Thunström Linda , Noy Shiri
Published: September 2019

A standard response of both policy makers and private citizens to hardships—from natural disasters to mass shootings—is to offer “thoughts and prayers.” Critics argue that such gestures are meaningless and may obstruct structural reforms intended to mitigate catastrophes. In this study, we elicit the value of receiving thoughts and prayers from strangers following adversity. We find that Christians value thoughts and prayers from religious strangers and priests, while atheists and agnostics are “prayer averse”—willing to pay to avoid receiving prayers. Furthermore, while indifferent to receiving thoughts from other secular people, they negatively value thoughts from Christians.
Monitoring of switches in heterochromatin-induced silencing shows incomplete establishment and developmental instabilities
Authors: Bughio Farah , Huckell Gary R. , Maggert Keith A.
Published: September 2019

Significance

The genetic properties of heterochromatin can create strikingly random patterns of inherited gene-expression states in otherwise identical cells. The origin of these patterns of clonal expression variation are not understood: How and when in development it is determined how many cells will express, how expression states are inherited through DNA replication, and how often instabilities arise. We developed genetic, mathematical, and molecular–genetic approaches to investigate these questions. Our results indicate that these characteristics are predetermined before chromatin structure is set, and the inheritance displays remarkable instability through development.
Structural insights into diverse modes of ICAM-1 binding by
Plasmodium falciparum
-infected erythrocytes
Authors: Lennartz Frank , Smith Cameron , Craig Alister G. , Higgins Matthew K.
Published: September 2019

A major determinant of pathogenicity in malaria caused by
Plasmodium falciparum
is the adhesion of parasite-infected erythrocytes to the vasculature or tissues of infected individuals. This occludes blood flow, leads to inflammation, and increases parasitemia by reducing spleen-mediated clearance of the parasite. This adhesion is mediated by PfEMP1, a multivariant family of around 60 proteins per parasite genome which interact with specific host receptors. One of the most common of these receptors is intracellular adhesion molecule-1 (ICAM-1), which is bound by 2 distinct groups of PfEMP1, A-type and B or C (BC)-type. Here, we present the structure of a domain from a B-type PfEMP1 bound to ICAM-1, revealing a complex binding site. Comparison with the existing structure of an A-type PfEMP1 bound to ICAM-1 shows that the 2 complexes share a globally similar architecture. However, while the A-type PfEMP1 bind ICAM-1 through a highly conserved binding surface, the BC-type PfEMP1 use a binding site that is more diverse in sequence, similar to how PfEMP1 interact with other human receptors. We also show that A- and BC-type PfEMP1 present ICAM-1 at different angles, perhaps influencing the ability of neighboring PfEMP1 domains to bind additional receptors. This illustrates the deep diversity of the PfEMP1 and demonstrates how variations in a single domain architecture can modulate binding to a specific ligand to control function and facilitate immune evasion.
Climate drives loss of phylogenetic diversity in a grassland community
Authors: Li Daijiang , Miller Jesse E. D. , Harrison Susan
Published: September 2019

While climate change has already profoundly influenced biodiversity through local extinctions, range shifts, and altered interactions, its effects on the evolutionary history contained within sets of coexisting species—or phylogenetic community diversity—have yet to be documented. Phylogenetic community diversity may be a proxy for the diversity of functional strategies that can help sustain ecological systems in the face of disturbances. Under climatic warming, phylogenetic diversity may be especially vulnerable to decline in plant communities in warm, water-limited regions, as intensified water stress eliminates drought-intolerant species that may be relicts of past wetter climates and may be distantly related to coexisting species. Here, we document a 19-y decline of phylogenetic diversity in a grassland community as moisture became less abundant and predictable at a critical time of the year. This decline was strongest in native forbs, particularly those with high specific leaf area, a trait indicating drought sensitivity. This decline occurred at the small spatial scale where species interact, but the larger regional community has so far been buffered against loss of phylogenetic diversity by its high levels of physical and biotic heterogeneity.
The role of atypical constellations in the grammaticalization
of German and English passives
Authors: Smirnova Elena , Mailhammer Robert , Flach Susanne
Published: September 2019

In this paper we propose an alternative scenario for the
grammaticalization of passive constructions in German and English. According to
the received view, the development starts with the frequent combinations of
copula verbs with past participles, which then increasingly gain in frequency
during the grammaticalization process. In contrast to the received view, we
argue that marginal – i.e., atypical and infrequent – constellations of
constructions play an important role in the grammaticalization process. These
constellations are ambiguous in their interpretation, and consequently have an
inherent potential to trigger semantic reinterpretation and syntactic
reanalysis. The alternative scenario is more consistent with theoretical
considerations and the patterns in corpus data of German and English between
1050 and 1350. Our paper supports the hypothesis that the grammaticalization of
the passive in German started from constellations of the become copula
with past participles of atelic verbs, i.e., activities and semelfactives. By
contrast, no such change can be observed in the corresponding construction in
English. We discuss the implications of our findings for constructional change
and grammaticalization in general.
Making the most of an early start to L2 instruction
Authors: Pfenninger Simone E. , Singleton David
Published: September 2019

Research over more than forty years has shown consistently that earlier L2 starters do not in the long term maintain the linguistic advantage of an early start over older starters. What, then, in the light of the widespread setting aside of the evidence regarding the apparent uselessness of an early start, is one to advise in respect of early L2 instruction? In this paper we discuss four factors which emerge as perhaps having relevance in this regard: the role of (bi)literacy skills, the role of language learning motivation, the role of factors relating to the transition from primary to secondary school, and the role of intensity of L2 instruction. We suggest that there are a number of broader macro-institutional factors, such as the impact of classroom experiences, that may impede the goal sought by the offering of numerous years of continued FL instruction.