bluuebunny/crossref_metadata_2025_split huggingface dataset:
PDEparams: parameter fitting toolbox for partial differential equations in python
Authors: Parra-Rojas César , Hernandez-Vargas Esteban A 
Published: December 2019

AbstractMotivationPartial differential equations (PDEs) is a well-established and powerful tool to simulate multi-cellular biological systems. However, available free tools for validation against data are on development.ResultsThe PDEparams module provides a flexible interface and readily accommodates different parameter analysis tools in PDE models such as computation of likelihood profiles, and parametric bootstrapping, along with direct visualization of the results. To our knowledge, it is the first open, freely available tool for parameter fitting of PDE models.Availability and implementationPDEparams is distributed under the MIT license. The source code, usage instructions and examples are freely available on GitHub at github.com/systemsmedicine/PDE_params.Supplementary informationSupplementary data are available at Bioinformatics online.
A missing touch of Adam Smith in Amartya Sen’s account of public reasoning: the man within for the man without
Authors: Bréban Laurie , Gilardone Muriel 
Published: December 2019

AbstractSen claims that his 2009 theory of justice is based in part upon Smith’s idea of the ‘impartial spectator’. His claim has received criticism: some authors have responded that his interpretation of Smith’s concept is unfaithful to the original; others, focussing on internal features of Sen’s analysis, critique his use of the Smithian impartial spectator, arguing that it is a weak point in his comparative theory of justice. In this paper, we address both sets of criticisms. While agreeing with commentators that Sen’s reading of Smith is somewhat unfaithful, we reiterate that his aim in The Idea of Justice is not to provide an exegesis of Smith but rather to build his own comparative theory of justice by ‘extending Adam Smith’s idea of the impartial spectator’ (IJ: 134) to his own project. After clarifying their distinct approaches to the concept of the impartial spectator, we draw upon our account of these differences to evaluate Sen’s own use of the concept. Despite significant divergences, we show that Sen’s version of the impartial spectator is not inconsistent with Smith’s analysis. Though it does not correspond to Smith’s concept, that is to what the Scottish philosopher sometimes calls the ‘man within’, it is reminiscent of another figure from Smith’s moral philosophy: the ‘man without’. Beyond this analogy, there are further connections between Smith’s imaginary figure of the ‘man within’ and Sen’s account of ‘common beliefs’—both notions are ways of representing our beliefs regarding what is moral or just. But whereas Smith’s moral philosophy offers an analysis of the process by which the ‘man without’ influences the ‘man within’, nothing of that kind is to be found in Sen’s conception of public reasoning. And it is here that Smith’s famous concept of ‘sympathy’ can supplement Sen’s theory, in a way that furnishes an answer to Shapiro’s (2011) criticism regarding the possibility of spontaneous change of beliefs towards greater impartiality.
Cell Architecture of the Giant Sulfur Bacterium Achromatium oxaliferum: Extra-cytoplasmic Localization of Calcium Carbonate Bodies
Authors: Schorn Sina , Salman-Carvalho Verena , Littmann Sten , Ionescu Danny , Grossart Hans-Peter , Cypionka Heribert 
Published: December 2019

ABSTRACTAchromatium oxaliferum is a large sulfur bacterium easily recognized by large intracellular calcium carbonate bodies. Although these bodies often fill major parts of the cells’ volume, their role and specific intracellular location are unclear. In this study, we used various microscopy and staining techniques to identify the cell compartment harboring the calcium carbonate bodies. We observed that Achromatium cells often lost their calcium carbonate bodies, either naturally or induced by treatments with diluted acids, ethanol, sodium bicarbonate and UV radiation which did not visibly affect the overall shape and motility of the cells (except for UV radiation). The water-soluble fluorescent dye fluorescein easily diffused into empty cavities remaining after calcium carbonate loss. Membranes (stained with Nile Red) formed a network stretching throughout the cell and surrounding empty or filled calcium carbonate cavities. The cytoplasm (stained with FITC and SYBR Green for nucleic acids) appeared highly condensed and showed spots of dissolved Ca2+ (stained with Fura-2). From our observations, we conclude that the calcium carbonate bodies are located in the periplasm, in extra-cytoplasmic pockets of the cytoplasmic membrane and are thus kept separate from the cell's cytoplasm. This periplasmic localization of the carbonate bodies might explain their dynamic formation and release upon environmental changes.
Large Fecal Reservoir of Escherichia coli Sequence Type 131-H30 Subclone Strains That Are Shared Within Households and Resemble Clinical ST131-H30 Isolates
Authors: Mohamed Muhanad , Clabots Connie , Porter Stephen B , Bender Tricia , Thuras Paul , Johnson James R 
Published: December 2019

Abstract

Background
Emerging antimicrobial-resistant Escherichia coli represent mainly the nested (fluoroquinolone-resistant [FQR]) H30R and H30Rx subclones within sequence type 131 (ST131). Intestinal colonization and within-household transmission may underlie H30R’s emergence.

Methods
We screened fecal samples from 741 volunteers (383 veterans, 358 household members, including pets) for ST131 and FQR E. coli (FQREC) and used molecular profiling to resolve unique strains. Selected strains underwent PCR-based detection of phylogroups, sequence types (STs), H30, H30Rx, and 53 virulence genes (VGs). Within-household strain sharing was compared with household, host, and bacterial characteristics. Fecal isolates were compared with clinical isolates.

Results
Colonization prevalence was 5.1% for H30R, 8% for ST131 (67% FQREC), and 10% for FQREC (52% ST131). ST131 isolates exhibited more VGs than non-ST131 isolates. Strain sharing (27% of multisubject households, 18% of corresponding subjects) was associated with the elderly, FQREC, H30R, H30Rx, ST73, and specific VGs. Fecal ST131 and FQREC isolates resembled contemporaneous and historical clinical isolates according to all studied traits.

Conclusions
Veterans and their human household members commonly carry and extensively share FQREC, predominantly H30R, thereby likely facilitating the ST131 pandemic. Strain sharing corresponds with multiple bacterial characteristics, including FQ resistance and specific VGs, which may promote intestinal colonization and/or host-to-host transmission.
A stitch in time: narrative review of interventions to reduce preterm births in Malawi
Authors: Batura Rekha , Colbourn Tim 
Published: December 2019

AbstractBackgroundThe rising rate of preterm births (PTBs) is a global concern, and Malawi has a high rate of PTBs (10.5%). The resulting neonatal and under-5 mortality, morbidity and lifelong disability represent a significant loss of human potential affecting individuals, families and society as a whole. This study aims to review the literature to determine the risk factors for PTB in Malawi and to identify effective interventions to prevent PTBs.MethodsA literature search yielded 22 studies that were categorized according to risk factors implicated for PTBs and health interventions to reduce the risks.ResultsThe study has shown that maternal pregnancy factors, infections, nutrition, anaemia and young maternal age are the main causes and risk factors of PTBs in Malawi. The literature revealed no evidence of community-based interventions for reducing the rates of PTBs in Malawi.ConclusionsAny successful effort to reduce the rate of PTBs will require a multisector, multilevel strategy targeted at the community, homes and individuals as a package to improve the education, nutrition and reproductive health of girls and women as well as focus on improving the delivery of antenatal services in the community.
HIV MDR is still a relevant issue despite its dramatic drop over the years
Authors: Armenia D , Di Carlo D , Flandre P , Bouba Y , Borghi V , Forbici F , Bertoli A , Gori C , Fabeni L , Gennari W , Pinnetti C , Mondi A , Cicalini S , Gagliardini R , Vergori A , Bellagamba R , Malagnino V , Montella F , Colafigli M , Latini A , Marocco R , Licthner M , Andreoni M , Mussini C , Ceccherini-Silberstein F , Antinori A , Perno C F , Santoro M M 
Published: December 2019

AbstractObjectivesTo evaluate the prevalence and therapeutic relevance of drug resistance among isolates from ART-experienced HIV-1-infected patients over the past two decades in Italy.MethodsDynamics of resistance to one, two and three or more antiretroviral classes were evaluated from 1999–2018. Virological success (VS) after the latest therapy switch was evaluated according to cumulative class resistance and cumulative genotypic susceptibility score (Stanford HIV_DB algorithm).ResultsAmong 13 663 isolates (from 6739 patients), resistance to at least one drug class decreased sharply from 1999 to 2010 (≤2001, 84.6%; 2010, 43.6%; P &lt; 0.001), then remained relatively constant at ∼40% during 2010–18, with the proportion of resistance to three or more classes also stable (∼5%). After 2008, integrase inhibitor resistance slightly increased from 5.6% to 9.7% in 2018 and contributed to resistance, particularly in isolates with resistance to three or more classes (one class, 8.4%; two classes, 15.3%; three or more classes, 34.7%, P &lt; 0.001). Among 1827 failing patients with an available follow-up, by 1 year after genotype-guided therapy start the probability of VS was 87.6%. Patients with cumulative resistance to three or more classes and receiving a poorly active regimen showed the lowest probability (62.6%) of VS (P &lt; 0.001) compared with all other patients (≥81.8%). By Cox regression analysis, cumulative MDR and receiving poorly active antiretroviral regimens were associated with a lower hazard of VS compared with those without resistance.ConclusionsA dramatic drop of HIV-1 drug resistance at failure has been achieved over the last two decades in Italy; resistance to three or more classes is low but present among currently failing patients. Its management still requires a rational and careful diagnostic and therapeutic approach.
On the applicability of a renormalized Born series for seismic wavefield modelling in strongly scattering media
Authors: Huang Xingguo , Jakobsen Morten , Wu Ru-Shan 
Published: December 2019

Abstract
Scattering theory is the basis for various seismic modeling and inversion methods. Conventionally, the Born series suffers from an assumption of a weak scattering and may face a convergence problem. We present an application of a modified Born series, referred to as the convergent Born series (CBS), to frequency-domain seismic wave modeling. The renormalization interpretation of the CBS from the renormalization group prospective is described. Further, we present comparisons of frequency-domain wavefields using the reference full integral equation method with that using the convergent Born series, proving that both of the convergent Born series can converge absolutely in strongly scattering media. Another attractive feature is that the Fast Fourier Transform is employed for efficient implementations of matrix–vector multiplication, which is practical for large-scale seismic problems. By comparing it with the full integral equation method, we have verified that the CBS can provide reliable and accurate results in strongly scattering media.
Identification of Li-ion battery models through monotonic echo serial networks for coarse data
Authors: Álvarez-Caballero Antonio , Blanco Cecilio , Couso Inés , Sánchez Luciano 
Published: December 2019

Abstract
Monotone transformation models are extended to inaccurate data and are combined with recurrent neural networks in a new battery model that is able to ascertain the health of rechargeable batteries for automotive applications. The presented method exploits the information contained in the vehicle’s operational records better than other cutting-edge models and uses a minimum amount of human expert knowledge. The experimental validation of the technique includes a comparative analysis of batteries in different health conditions, comprising first-principles models and different machine learning procedures.
HER2-HER3 Heterodimer Quantification by FRET-FLIM and Patient Subclass Analysis of the COIN Colorectal Trial
Authors: Barber Paul R , Weitsman Gregory , Lawler Katherine , Barrett James E , Rowley Mark , Rodriguez-Justo Manuel , Fisher David , Gao Fangfei , Tullis Iain D C , Deng Jinhai , Brown Louise , Kaplan Richard , Hochhauser Daniel , Adams Richard , Maughan Timothy S. , Vojnovic Borivoj , Coolen Anthony C C , Ng Tony 
Published: December 2019

Abstract

Background
The phase III MRC COIN trial showed no statistically significant benefit from adding the EGFR-target cetuximab to oxaliplatin-based chemotherapy in first-line treatment of advanced colorectal cancer. This study exploits additional information on HER2-HER3 dimerization to achieve patient stratification and reveal previously hidden subgroups of patients who had differing disease progression and treatment response.

Methods
HER2-HER3 dimerization was quantified by fluorescence lifetime imaging microscopy in primary tumor samples from 550 COIN trial patients receiving oxaliplatin and fluoropyrimidine chemotherapy with or without cetuximab. Bayesian latent class analysis and covariate reduction was performed to analyze the effects of HER2-HER3 dimer, RAS mutation, and cetuximab on progression-free survival and overall survival (OS). All statistical tests were two-sided.

Results
Latent class analysis on a cohort of 398 patients revealed two patient subclasses with differing prognoses (median OS = 1624 days [95% confidence interval [CI] = 1466 to 1816 days] vs 461 days [95% CI = 431 to 504 days]): Class 1 (15.6%) showed a benefit from cetuximab in OS (hazard ratio = 0.43, 95% CI = 0.25 to 0.76, P = .004). Class 2 showed an association of increased HER2-HER3 with better OS (hazard ratio = 0.64, 95% CI = 0.44 to 0.94, P = .02). A class prediction signature was formed and tested on an independent validation cohort (n = 152) validating the prognostic utility of the dimer assay. Similar subclasses were also discovered in full trial dataset (n = 1630) based on 10 baseline clinicopathological and genetic covariates.

Conclusions
Our work suggests that the combined use of HER dimer imaging and conventional mutation analyses will be able to identify a small subclass of patients (&gt;10%) who will have better prognosis following chemotherapy. A larger prospective cohort will be required to confirm its utility in predicting the outcome of anti-EGFR treatment.
Structural analysis of disc super star clusters of M82: size and profile shape at intermediate ages
Authors: Cuevas-Otahola B , Mayya Y D , Puerari I , Rosa-González D 
Published: December 2019

ABSTRACT
We present the structural parameters of 99 super star clusters (SSCs) in the disc of M82. Moffat-EFF, King, and Wilson models were fitted using a χ2-minimization method to background-subtracted surface brightness profiles in the F435W (B), F555W (V), and F814W (I) bands of the Advanced Camera for Surveys (ACS) of the Hubble Space Telescope. The majority of the SSC profiles are best fitted by the Moffat-EFF profile. The scale parameter rd and the shape parameter γ in the three filters are identical within the measurement errors. The analysed sample is big enough to allow the characterization of the distributions of core radii Rc and γ. The obtained distribution of Rc follows a lognormal form, with centre and $\sigma \mathrm{ log}\big {(}\frac{R_{\rm c}}{pc}\big {)}$ being 1.73 pc and 0.25, respectively. The γ distribution is also lognormal with centre and σlog(γ) being 2.88 and 0.08, respectively. M82 is well known for the absence of current star formation in its disc, with all disc SSCs older than 50 Myr and hardly any cluster older than ∼300 Myr. The derived distributions compare very well with the distributions for intermediate-age clusters in the Large Magellanic Cloud (LMC), which is also a low-mass late-type galaxy similar to M82. On the other hand, the distributions of Rc in both these galaxies are shifted towards larger values as compared to SSCs of similar age in the giant spiral galaxy M83. M82 and LMC also span a narrower range of γ values as compared to that in M83.
Evolution of giant molecular clouds across cosmic time
Authors: Guszejnov Dávid , Grudić Michael Y , Offner Stella S R , Boylan-Kolchin Michael , Faucher-Gigère Claude-André , Wetzel Andrew , Benincasa Samantha M , Loebman Sarah 
Published: December 2019

ABSTRACT
Giant molecular clouds (GMCs) are well studied in the local Universe, however, exactly how their properties vary during galaxy evolution is poorly understood due to challenging resolution requirements, both observational and computational. We present the first time-dependent analysis of GMCs in a Milky Way-like galaxy and an Large Magellanic Cloud (LMC)-like dwarf galaxy of the FIRE-2 (Feedback In Realistic Environments) simulation suite, which have sufficient resolution to predict the bulk properties of GMCs in cosmological galaxy formation self-consistently. We show explicitly that the majority of star formation outside the galactic centre occurs within self-gravitating gas structures that have properties consistent with observed bound GMCs. We find that the typical cloud bulk properties such as mass and surface density do not vary more than a factor of 2 in any systematic way after the first Gyr of cosmic evolution within a given galaxy from its progenitor. While the median properties are constant, the tails of the distributions can briefly undergo drastic changes, which can produce very massive and dense self-gravitating gas clouds. Once the galaxy forms, we identify only two systematic trends in bulk properties over cosmic time: a steady increase in metallicity produced by previous stellar populations and a weak decrease in bulk cloud temperatures. With the exception of metallicity, we find no significant differences in cloud properties between the Milky Way-like and dwarf galaxies. These results have important implications for cosmological star and star cluster formation and put especially strong constraints on theories relating the stellar initial mass function to cloud properties.
CBMS-03 PHOSPHORYLATION STATE OF OLIG2 REGULATES PROLIFERATION OF GLIOMA STEM CELLS
Authors: Saito Norihiko , Hirai Nozomi , Aoki Kazuya , Sato Sho , Suzuki Ryo , Hiramoto Yu , Fujita Satoshi , Nakayama Haruo , Hayashi Morito , Sakurai Takatoshi , Iwabuchi Satoshi 
Published: December 2019

Abstract
The Cancer Genome Atlas project described a robust gene expression-based molecular classification of glioblastoma with the functional and biological significance of the subclasses yet to be determined. Here, we show that a comprehensive analysis of a panel of glioma initiating cell (GIC) lines can identify a group of stem cells with high OLIGg2 expression as in Proneural-like GBM subtype. In vitro differentiation studies showed that proneural GIC lines possess the potential to differentiate into astrocytic, neuronal, and oligodendrocytic lineages, whereas mesenchymal GICs exhibited limited potential for neural lineage differentiation following retinoic acid induction. A considerable decline of OLIG2 in proneural GIC lines was observed following retinoic acid treatment. We also showed that OLIG2 is a functional marker associated with cell proliferation in Olig2-high GIC lines. In addition, OLIG2 inhibition disrupted cell-cycle control mechanism by decreasing CDK2 and CDK4 and elevating apoptosis-related molecules. Mechanistic investigations revealed molecular interactions between CDK2/CDK4 and OLIG2. Inhibition of CDK2/CDK4 activity disrupted OLIG2-CDK2/CDK4 interactions and attenuated OLIG2 protein stability. Further investigation on these mechanisms may lead to novel targeted therapy on GBMs with high OLIG2 expression.
SPDR-05 PARP INHIBITORS RESTORE TEMOZOLOMIDE SENSITIVITY IN MSH6-DEFICIENT TEMOZOLOMIDE-RESISTANT GLIOBLASTOMA CELLS
Authors: Higuchi Fumi , Nagashima Hiroaki , Wakimoto Hiroaki , Daniel P Cahill 
Published: December 2019

Abstract

INTRODUCTION
Mismatch repair (MMR) deficiency through MSH6 inactivation has been identified in approximately 25% of recurrent gliomas. This MMR deficiency represents a key molecular mechanism of acquired resistance to the alkylating chemotherapeutic agent temozolomide (TMZ). Potentiation of TMZ-induced cytotoxicity by PARP inhibitors (PARPi) has been reported in several cancers including gliomas. However, mechanisms that underlie the PARPi-mediated chemo-potentiation and biomarkers that predict benefit from this combination treatment have not been identified in gliomas. We investigated whether PARPis could restore TMZ sensitivity of MSH6-deficient chemoresistant gliomas and assessed the role of the base excision repair (BER) DNA damage repair pathway in PARPi-mediated effects.

METHODS
We engineered glioblastoma cell lines and patient-derived glioblastoma neurosphere lines to knockdown MSH6 expression, resulting in acquired MMR-deficient resistance to TMZ. We treated these isogenic pairs of MSH6 wild type and MSH6-inactivated cells with TMZ, PARPi Veriparib or Olaparib, and combination. Using MSH6-deficient glioma xenografts, we tested the in vivo efficacy of veliparib in combination with TMZ. We used genetic and pharmacological approaches to assess the role of BER pathway in PARPi-mediated effects.

RESULTS
We found that combination with PARPi restored TMZ sensitivity in MSH6-inactivated TMZ resistant cells whereas only subtle combination effects were seen in control MMR-proficient cells at the same PARPi concentrations. In vivo, combination treatment of TMZ with Veliparib demonstrated potent suppression of tumor growth of MSH6-inactivated orthotopic and flank xenografts, compared with TMZ monotherapy. Unlike PARPi, genetic and pharmacological blockage of BER pathway did not re-sensitize MSH6-inactivated cells to TMZ.

CONCLUSION
PARPis restore TMZ sensitivity in MSH6-deficient glioblastoma cells. This combination treatment is a promising strategy to target acquired chemoresistance caused by MMR deficiency.