bluuebunny/crossref_metadata_2025_split huggingface dataset:
Charged spherically symmetric Taub–NUT black hole solutions in $f(R)$ gravity
Authors: Nashed G G L , Bamba Kazuharu 
Published: February 2020

Abstract
$f(R)$ theory is a modification of Einstein’s general relativity which has provided many interesting results in cosmology and astrophysics. To derive a black hole solution in this theory is difficult due to the fact that it contains fourth-order differential equations. In this study, we use the first reliable deviation from general relativity which is given by the quadratic form of $f(R)=R+\beta R^2$, where $\beta$ is a dimensional parameter. We calculate the energy conditions of charged black holes and show that they are all satisfied for the Taub–NUT spacetime. Finally, we study some thermodynamic quantities such as entropy, temperature, specific heat, and Gibbs free energy. The calculations of heat capacity and free energy show that the charged Taub–NUT black hole has positive values, which means that it has thermal stability.
Short-term effects of air pollution on daily asthma-related emergency department visits in an industrial city
Authors: AlBalawi Salem M , Namdeo Anil , Hodgson Susan , Pless-Mulloli Tanja , McNally Richard J Q 
Published: February 2020

Abstract

Background
Epidemiological studies from Europe and North America have provided evidence that exposure to air pollution can aggravate symptoms in asthmatic patients.

Methods
Daily number of AEDv, air pollution levels (PM10, PM2.5, SO2, NO2 and CO) and meteorological variables was obtained from Jubail Industrial City, Saudi Arabia, for the period of 2007–11. Data were analyzed using a time-series approach. Relative risks (RRs) were estimated using Poisson regression.

Results
The associations between AEDv and PM10, PM2.5, SO2 and NO2 remained positive and statistically significant after mutual adjustment in the multi-pollutant model.
The RR of AEDv increased by 5.4, 4.4, 3.4 and 2.2% per an inter-quartile range increase in SO2 (2.0 ppb), PM2.5 (36 μg/m3), NO2 (7.6 ppb) and PM10 (140 μg/m3), respectively. No significant associations between AEDv and CO were found.

Conclusions
Current levels of ambient air pollution are associated with AEDv in this industrial setting in the Middle East. Greater awareness of environmental health protection and the implementation of effective measures to improve the quality of air in such settings would be beneficial to public health.
Molecular epidemiology, in vitro susceptibility and exoenzyme screening of Malassezia clinical isolates
Authors: Li Wei , Zhang Zi-Wei , Luo Yun , Liang Ni , Pi Xiao-Xue , Fan Yi-Ming 
Published: February 2020

Introduction.Malasseziafolliculitis (MF) and pityriasis versicolor (PV) are common dermatoses caused byMalasseziaspecies. Their molecular epidemiology, drug susceptibility and exoenzymes are rarely reported in China.Aim.To investigate the molecular epidemiology, drug susceptibility and enzymatic profile ofMalasseziaclinical isolates.Methodology.Malasseziastrains were recovered from MF and PV patients and healthy subjects (HS) and identified by sequencing analysis. The minimum inhibitory concentrations (MICs) of nine antifungals (posaconazole, voriconazole, itraconazole, fluconazole, ketoconazole, miconazole, bifonazole, terbinafine and caspofungin) and tacrolimus, the interactions between three antifungals (itraconazole, ketoconazole and terbinafine) and tacrolimus, and the extracellular enzyme profile were evaluated using broth and checkerboard microdilution and the Api-Zym system, respectively.Results.Among 392Malasseziaisolates from 729 subjects (289 MF, 218 PV and 222 HS),Malassezia furfurandMalassezia globosaaccounted for 67.86 and 18.88 %, respectively.M. furfurwas the major species in MF and PV patients and HS. Among 60M.furfurand 50M.globosastrains, the MICs for itraconazole, posaconazole, voriconazole and ketoconazole were <1 μg ml−1.M. furfurwas more susceptible to itraconazole, terbinafine and bifonazole but tolerant to miconazole compared withM. globosa(P<0.05). Synergistic effects between terbinafine and itraconazole or between tacrolimus and itraconazole, ketoconazole or terbinafine occurred in 6, 7, 6 and 9 out of 37 strains, respectively. Phosphatases, lipases and proteases were mainly secreted in 51 isolates.Conclusions.Itraconazole, posaconazole, voriconazole and ketoconazole are theagents against which there is greatest susceptibility. Synergistic effects between terbinafine and itraconazole or tacrolimas and antifungals may be irrelevant to clinical application. Overproduction of lipases could enhance the skin inhabitation ofM. furfur.
Can Search Query Forecast successfully in China’s novel coronavirus (2019-nCov) pneumonia?
Authors: Xiaoxuan LI , Qi WU , Bbenfu Lv 
Published: February 2020

AbstractRecently the novel coronavirus (2019-nCov) pneumonia outbreak in China then the world, and the Number of infections and death continues to increases. Search Query performs well in forecasting the epidemics. It is still a question whether search engine data can forecast the drift and the inflexion in 2019-nCov pneumonia. Based on the Baidu Search Index, we propose three prediction models: composite Index, composite Index with filtering and suspected NCP(Novel Coronavirus Pneumonia). The result demonstrates that the predictive model of composite index with filtering performs the best while the model of suspected NCP has the highest forecast error. We further predict the out-of-the-set NCP confirmed cases and monitor that the next peak of new diagnoses will occur on February 16thand 17th.
Estimating the distribution of the incubation period of 2019 novel coronavirus (COVID-19) infection between travelers to Hubei, China and non-travelers
Authors: Leung Char 
Published: February 2020

AbstractObjectivesAmid the continuing spread of the novel coronavirus (COVID-19), the incubation period of COVID-19 should be regularly re-assessed as more information is available upon the increase in reported cases. The present work estimated the distribution of incubation periods of patients infected in and outside Hubei province of China.MethodsClinical data were collected from the individual cases reported by the media as they were not fully available on the official pages of the Chinese health authorities. MLE was used to estimate the distributions of the incubation period.ResultsIt was found that the incubation period of patients with no travel history to Hubei was longer and more volatile.ConclusionIt is recommended that the duration of quarantine should be extended to at least 3 weeks.
Cohort Profile: The China Multi-Ethnic Cohort (CMEC) Study
Authors: Zhao Xing , Hong Feng , Yin Jianzhong , Tang Wenge , Zhang Gang , Liang Xian , Li Jingzhong , Cui Chaoying , Li Xiaosong 
Published: February 2020

AbstractCohort purposeThe China Multi-Ethnic Cohort (CMEC) is a community population-based prospective observational study aiming to address the urgent need for understanding NCD prevalence, risk factors and associated conditions in resource-constrained settings for ethnic minorities in China.Cohort BasicsA total of 99 556 participants aged 30 to 79 years (Tibetan populations include those aged 18 to 30 years) from the Tibetan, Yi, Miao, Bai, Bouyei, and Dong ethnic groups in Southwest China were recruited between May 2018 and September 2019.Follow-up and attritionAll surviving study participants will be invited for re-interviews every 3-5 years with concise questionnaires to review risk exposures and disease incidence. Furthermore, the vital status of study participants will be followed up through linkage with established electronic disease registries annually.Design and MeasuresThe CMEC baseline survey collected data with an electronic questionnaire and face-to-face interviews, medical examinations and clinical laboratory tests. Furthermore, we collected biological specimens, including blood, saliva and stool, for long-term storage. In addition to the individual level data, we also collected regional level data for each investigation site.Collaboration and data accessCollaborations are welcome. Please send specific ideas to corresponding author at: xingzhao@scu.edu.cn.
Endosidin20 targets cellulose synthase catalytic domain to inhibit cellulose biosynthesis
Authors: Huang Lei , Li Xiaohui , Zhang Weiwei , Ung Nolan , Liu Nana , Yin Xianglin , Li Yong , Mcewan Robert E. , Dilkes Brian , Dai Mingji , Hicks Glenn R. , Raikhel Natasha V. , Staiger Christopher J. , Zhang Chunhua 
Published: February 2020

AbstractCellulose is synthesized by rosette structured cellulose synthase (CESA) complexes (CSCs), each of which is composed of multiple units of CESAs in three different isoforms. CSCs rely on vesicle trafficking for delivery to the plasma membrane where they catalyze cellulose synthesis. Although the rosette structured CSCs were observed decades ago, it remains unclear what amino acids in plant CESA that directly participate in cellulose catalytic synthesis. It is also not clear how the catalytic activity of CSCs influences their efficient transport at the subcellular level. Here we report characterization of the small molecule Endosidin20 (ES20) and present evidence that it represents a new CESA inhibitor. We show data from chemical genetic analyses, biochemical assays, structural modeling, and molecular docking to support our conclusion that ES20 targets the catalytic site of Arabidopsis CESA6. Further, chemical genetic analysis reveals important amino acids that potentially form the catalytic site of plant CESA6. Using high spatiotemporal resolution live-cell imaging, we found that inhibition of CSC catalytic activity by inhibitor treatment, or by creating missense mutation at amino acids in the predicted catalytic site, causes reduced efficiency in CSC transport to the plasma membrane. Our results show that the catalytic activity of plant CSCs is integrated with subcellular trafficking dynamics.One sentence summaryEndosidin20 targets cellulose synthase at the catalytic site to inhibit cellulose synthesis and the inhibition of catalytic activity reduces cellulose synthase complex delivery to the plasma membrane.
Coordinated assembly and release of adhesions builds apical junctional belts duringde novopolarisation of an epithelial tube
Authors: Symonds Andrew C , Buckley Clare E , Williams Charlotte A , Clarke Jonathan DW 
Published: February 2020

AbstractUsing the zebrafish neural tube as a model, we uncover thein vivomechanisms allowing the generation of two opposing apical epithelial surfaces within the centre of an initially unpolarised, solid organ. We show that NOK/Pals1/Mpp5a and Rab11a play a dual role in coordinating the generation of ipsilateral junctional belts whilst simultaneously releasing contralateral adhesions across the centre of the tissue. We show that Nok and Rab11a mediated resolution of cell-cell adhesions are both necessary for midline lumen opening and contribute to later maintenance of epithelial organisation. We propose these roles for both Nok and Rab11a operate through the transmembrane protein Crumbs. In light of a recent conflicting publication, we also clarify that the junction remodelling role of Nok is not specific to dividing cells.
Role of nanoscale antigen organization on B-cell activation probed using DNA origami
Authors: Veneziano Rémi , Moyer Tyson J. , Stone Matthew B. , Shepherd Tyson R. , Schief William R. , Irvine Darrell J. , Bathe Mark 
Published: February 2020

ABSTRACTArraying vaccine immunogens in a multivalent form on the surface of virus-like particles is an important strategy used to enhance the efficacy of subunit vaccines. However, the impacts of antigen valency, spacing, and spatial organization on B cell triggering remain poorly understood. Here, we use DNA origami nanoparticles to create precise nanoscale organizations of a clinically-relevant HIV gp120 immunogen to systematically interrogate their impact on B cell triggeringin vitro. We find that antigen dimers elicit monotonically increasing B cell receptor activation as inter-antigen spacing increases up to ~30 nm, and only 5 immunogens arrayed on the surface of a 3D particle are needed to elicit maximal B cell calcium signaling. Our results reveal design principles of viral and immunogen display that drive functional B cell responses.
High antibody titres induced by protein subunit vaccines against Buruli ulcer usingMycobacterium ulceransantigens Hsp18 and MUL_3720
Authors: Mangas Kirstie M. , Tobias Nicholas , Marion Estelle , Babonneau Jérémie , Marsollier Laurent , Porter Jessica L. , Pidot Sacha J. , Wong Chinn Yi , Jackson David C. , Chua Brendon Y. , Stinear Timothy P. 
Published: February 2020

AbstractBackgroundMycobacterium ulceransis the causative agent of a debilitating skin and soft tissue infection known as Buruli ulcer (BU). There is no vaccine against BU. The purpose of this study was to investigate the vaccine potential of two previously described immunogenicM. ulceransproteins, MUL_3720 and Hsp18, using a mouse tail infection model of BU.MethodsRecombinant versions of the two proteins were each electrostatically coupled with a previously described lipopeptide adjuvant. Seven C57BL/6 and seven BALB/c mice were vaccinated and boosted with each of the formulations. Vaccinated mice were then challenged withM. ulceransvia subcutaneous tail inoculation. Vaccine performance was assessed by time-to-ulceration compared to unvaccinated mice.ResultsThe MUL_3720 and Hsp18 vaccines induced high titres of antigen-specific antibodies that were predominately subtype IgG1. However, all mice developed ulcers by day-40 post-M. ulceranschallenge. No significant difference was observed in the time-to-onset of ulceration between the experimental vaccine groups and unvaccinated animals.ConclusionsThese data align with previous vaccine experiments using Hsp18 and MUL_3720 that indicated these proteins may not be appropriate vaccine antigens. This work highlights the need to explore alternative vaccine targets and different approaches to understand the role antibodies might play in controlling BU.
Adaptation of pancreatic cancer cells to nutrient deprivation is reversible and requires glutamine synthetase stabilization by mTORC1
Authors: Tsai Pei-Yun , Lee Min-Sik , Jadhav Unmesh , Naqvi Insia , Madha Shariq , Adler Ashley , Mistry Meeta , Naumenko Sergey , Lewis Caroline A. , Hitchcock Daniel S. , Roberts Frederick R. , DelNero Peter , Hank Thomas , Honselmann Kim C. , Oyarvide Vicente Morales , Mino-Kenudson Mari , Clish Clary B. , Shivdasani Ramesh A. , Kalaany Nada Y. 
Published: February 2020

AbstractPancreatic ductal adenocarcinoma (PDA) is a lethal, therapy-resistant cancer that thrives in a highly desmoplastic, nutrient-deprived microenvironment. Several studies investigated the effects of depriving PDA of either glucose or glutamine alone. However, the consequences on PDA growth and metabolism of limiting both preferred nutrients have remained largely unknown. Here, we report the selection for clonal human PDA cells that survive and adapt to limiting levels of both glucose and glutamine. We find that adapted clones exhibit increased growth in vitro and enhanced tumor-forming capacity in vivo. Mechanistically, adapted clones share common transcriptional and metabolic programs, including amino acid use for de novo glutamine and nucleotide synthesis. They also display enhanced mTORC1 activity that prevents the proteasomal degradation of glutamine synthetase (GS), the rate-limiting enzyme for glutamine synthesis. This phenotype is notably reversible, with PDA cells acquiring alterations in open chromatin upon adaptation. Silencing of GS suppresses the enhanced growth of adapted cells and mitigates tumor growth. These findings identify non-genetic adaptations to nutrient deprivation in PDA and highlight GS as a dependency that could be targeted therapeutically in pancreatic cancer patients.SignificancePancreatic ductal adenocarcinoma (PDA) is a highly lethal malignancy with no effective therapies. PDA aggressiveness partly stems from its ability to grow within a uniquely dense stroma restricting nutrient access. This study demonstrates that PDA clones that survive chronic nutrient deprivation acquire reversible non-genetic adaptations allowing them to switch between metabolic states optimal for growth under nutrient-replete or nutrient-deprived conditions. One contributing factor to this adaptation mTORC1 activation, which stabilizes glutamine synthetase (GS) necessary for glutamine generation in nutrient-deprived cancer cells. Our findings imply that although total GS levels may not be a prognostic marker for aggressive disease, GS inhibition is of high therapeutic value, as it targets specific cell clusters adapted to nutrient starvation, thus mitigating tumor growth.
Whole exome precision oncology targeting synthetic lethal vulnerabilities across the tumor transcriptome
Authors: Lee Joo Sang , Nair Nishanth Ulhas , Chapman Lesley , Sinha Sanju , Wang Kun , Cha Houngui , Rubin Eitan , Berger Raanan , Lazar Vladimir , Kurzrock Razelle , Gilbert Mark R. , Hannenhalli Sridhar , Lee Se-Hoon , Aldape Kenneth , Ruppin Eytan 
Published: February 2020

AbstractPrecision oncology has made significant advances in the last few years, mainly by targeting actionable mutations in cancer driver genes. However, the proportion of patients whose tumors can be targeted therapeutically remains limited. Recent studies have begun to explore the benefit of analyzing tumor transcriptomics data to guide patient treatment, raising the need for new approaches for systematically accomplishing that. Here we show that computationally derived genetic interactions can successfully predict patient response. Assembling a broad repertoire of 32 datasets spanning more than 1,500 patients and including both tumor transcriptomics and response data, we predicted the response in 17 out of 21 targeted and 8 out of 11 checkpoint therapy datasets across 8 different cancer types with considerable accuracy, without ever training on these datasets. Analyzing the recently published multi-arm WINTHER trial, we show that the fraction of patients benefitting from transcriptomic-based treatments could potentially be markedly increased from 15% to about 85% by targeting synthetic lethal vulnerabilities in their tumors. In summary, this is the first computational approach to obtain considerable predictive performance across many different targeted and immunotherapy datasets, providing a promising new way for guiding cancer treatment based on the tumor transcriptomics of cancer patients.
CRISPR-mediated isogenic cell-SELEX approach for generating highly specific aptamers against native membrane proteins
Authors: Rosch Jonah C. , Neal Emma H. , Balikov Daniel A. , Rahim Mohsin , Lippmann Ethan S. 
Published: February 2020

AbstractIntroductionThe generation of affinity reagents that bind native membrane proteins with high specificity remains challenging. Mostin vitroselection paradigms utilize different cell types for positive and negative rounds of selection (where the positive selection is against a cell that expresses the desired membrane protein and the negative selection is against a cell that lacks the protein). However, this strategy can yield affinity reagents that bind unintended membrane proteins on the target cells. To address this issue, we developed a systematic evolution of ligands by exponential enrichment (SELEX) scheme that utilizes isogenic pairs of cells generated via CRISPR techniques.MethodsUsing a Caco-2 epithelial cell line with constitutive Cas9 expression, we knocked out theSLC2A1gene (encoding the GLUT1 glucose transporter) via lipofection with synthetic gRNAs. Cell-SELEX rounds were carried out against wild-type and GLUT1-null cells using a single-strand DNA (ssDNA) library. Next-generation sequencing (NGS) was used to quantify enrichment of prospective binders to the wild-type cells.Results10 rounds of cell-SELEX were conducted via simultaneous exposure of ssDNA pools to wild-type and GLUT1-null Caco-2 cells under continuous perfusion. The top binders identified from NGS were validated by flow cytometry and immunostaining for their specificity to the GLUT1 receptor.ConclusionsOur data indicate that highly specific aptamers can be isolated with a SELEX strategy that utilizes isogenic cell lines. This approach should be broadly useful for generating affinity reagents that selectively bind to membrane proteins in their native conformations on the cell surface.
S-Trap eliminates cell culture media polymeric surfactants for effective proteomic analysis of mammalian cell bioreactor supernatants
Authors: Zacchi Lucia F. , Recinos Dinora Roche , Otte Ellen , Aitken Campbell , Hunt Tony , Sandford Vanessa , Lee Yih Yean , Schulz Benjamin L. , Howard Christopher B. 
Published: February 2020

AbstractProteomic analysis of bioreactor supernatants can inform on cellular metabolic status, viability, and productivity, as well as product quality, which can in turn help optimize bioreactor operation. Incubating mammalian cells in bioreactors requires the addition of polymeric surfactants such as Pluronic F68, which reduce the sheer stress caused by agitation. However, these surfactants are incompatible with mass spectrometry proteomics and must be eliminated during sample preparation. Here, we compared four different sample preparation methods to eliminate polymeric surfactants from filtered bioreactor supernatant samples: organic solvent precipitation; filter-assisted sample preparation (FASP); S-Trap; and single-pot, solid-phase, sample preparation (SP3). We found that SP3 and S-Trap substantially reduced or eliminated the polymer(s), but S-Trap provided the most robust clean-up and highest quality data. Additionally, we observed that SP3 sample preparation of our samples and in other published datasets was associated with partial alkylation of cysteines, which could impact the confidence and robustness of protein identification and quantification. Finally, we observed that several commercial mammalian cell culture media and media supplements also contained polymers with similar mass spectrometry profiles, and we suggest that proteomic analyses in these media will also benefit from the use of S-Trap sample preparation.