bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tumor purity quantification by clonal DNA methylation signatures
Authors: Benelli Matteo , Romagnoli Dario , Demichelis Francesca 
Published: January 2018

Abstract

Motivation
Controlling for tumor purity in molecular analyses is essential to allow for reliable genomic aberration calls, for inter-sample comparison and to monitor heterogeneity of cancer cell populations. In genome wide screening studies, the assessment of tumor purity is typically performed by means of computational methods that exploit somatic copy number aberrations.

Results
We present a strategy, called Purity Assessment from clonal MEthylation Sites (PAMES), which uses the methylation level of a few dozen, highly clonal, tumor type specific CpG sites to estimate the purity of tumor samples, without the need of a matched benign control. We trained and validated our method in more than 6000 samples from different datasets. Purity estimates by PAMES were highly concordant with other state-of-the-art tools and its evaluation in a cancer cell line dataset highlights its reliability to accurately estimate tumor admixtures. We extended the capability of PAMES to the analysis of CpG islands instead of the more platform-specific CpG sites and demonstrated its accuracy in a set of advanced tumors profiled by high throughput DNA methylation sequencing. These analyses show that PAMES is a valuable tool to assess the purity of tumor samples in the settings of clinical research and diagnostics.

Availability and implementation
https://github.com/cgplab/PAMES

Supplementary information
Supplementary data are available at Bioinformatics online.
Training and Spontaneous Reinforcement of Neuronal Assemblies by Spike Timing Plasticity
Authors: Ocker Gabriel Koch , Doiron Brent 
Published: January 2018

Abstract
The synaptic connectivity of cortex is plastic, with experience shaping the ongoing interactions between neurons. Theoretical studies of spike timing-dependent plasticity (STDP) have focused on either just pairs of neurons or large-scale simulations. A simple analytic account for how fast spike time correlations affect both microscopic and macroscopic network structure is lacking. We develop a low-dimensional mean field theory for STDP in recurrent networks and show the emergence of assemblies of strongly coupled neurons with shared stimulus preferences. After training, this connectivity is actively reinforced by spike train correlations during the spontaneous dynamics. Furthermore, the stimulus coding by cell assemblies is actively maintained by these internally generated spiking correlations, suggesting a new role for noise correlations in neural coding. Assembly formation has often been associated with firing rate-based plasticity schemes; our theory provides an alternative and complementary framework, where fine temporal correlations and STDP form and actively maintain learned structure in cortical networks.
Are We on Our Way to Achieving the 2020 Goals for Schistosomiasis Morbidity Control Using Current World Health Organization Guidelines?
Authors: Toor Jaspreet , Alsallaq Ramzi , Truscott James E , Turner Hugo C , Werkman Marleen , Gurarie David , King Charles H , Anderson Roy M 
Published: January 2018

Abstract

Background
Schistosomiasis remains an endemic parasitic disease affecting millions of people around the world. The World Health Organization (WHO) has set goals of controlling morbidity to be reached by 2020, along with elimination as a public health problem in certain regions by 2025. Mathematical models of parasite transmission and treatment impact have been developed to assist in controlling the morbidity caused by schistosomiasis. These models can inform and guide implementation policy for mass drug administration programs, and help design monitoring and evaluation activities.

Methods
We use these models to predict whether the guidelines set by the WHO are on track for achieving their 2020 goal for the control of morbidity, specifically for Schistosoma mansoni. We examine whether programmatic adaptations; namely increases in treatment coverage and/or expansion to adult inclusion in treatment, will improve the likelihood of reaching the WHO goals.

Results
We find that in low-prevalence settings, the goals are likely to be attainable under current WHO guidelines, but in moderate to high-prevalence settings, the goals are less likely to be achieved unless treatment coverage is increased and expanded to at least 85% for school-aged children and 40% for adults.

Conclusions
To improve the likelihood of reaching the WHO goals, programmatic adaptations are required, particularly for moderate- to high-prevalence settings. Furthermore, improvements in adherence to treatment, potential development of candidate vaccines, and enhanced snail control and WASH (water, sanitation, and hygiene) measures will all assist in achieving the goals.
Are Alternative Strategies Required to Accelerate the Global Elimination of Lymphatic Filariasis? Insights From Mathematical Models
Authors: Stolk Wilma A , Prada Joaquin M , Smith Morgan E , Kontoroupis Periklis , de Vos Anneke S , Touloupou Panayiota , Irvine Michael A , Brown Paul , Subramanian Swaminathan , Kloek Marielle , Michael E , Hollingsworth T Deirdre , de Vlas Sake J 
Published: January 2018

Abstract

Background
With the 2020 target year for elimination of lymphatic filariasis (LF) approaching, there is an urgent need to assess how long mass drug administration (MDA) programs with annual ivermectin + albendazole (IA) or diethylcarbamazine + albendazole (DA) would still have to be continued, and how elimination can be accelerated. We addressed this using mathematical modeling.

Methods
We used 3 structurally different mathematical models for LF transmission (EPIFIL, LYMFASIM, TRANSFIL) to simulate trends in microfilariae (mf) prevalence for a range of endemic settings, both for the current annual MDA strategy and alternative strategies, assessing the required duration to bring mf prevalence below the critical threshold of 1%.

Results
Three annual MDA rounds with IA or DA and good coverage (≥65%) are sufficient to reach the threshold in settings that are currently at mf prevalence &lt;4%, but the required duration increases with increasing mf prevalence. Switching to biannual MDA or employing triple-drug therapy (ivermectin, diethylcarbamazine, and albendazole [IDA]) could reduce program duration by about one-third. Optimization of coverage reduces the time to elimination and is particularly important for settings with a history of poorly implemented MDA (low coverage, high systematic noncompliance).

Conclusions
Modeling suggests that, in several settings, current annual MDA strategies will be insufficient to achieve the 2020 LF elimination targets, and programs could consider policy adjustment to accelerate, guided by recent monitoring and evaluation data. Biannual treatment and IDA hold promise in reducing program duration, provided that coverage is good, but their efficacy remains to be confirmed by more extensive field studies.
Achieving Viral Suppression in 90% of People Living With Human Immunodeficiency Virus on Antiretroviral Therapy in Low- and Middle-Income Countries: Progress, Challenges, and Opportunities
Authors: Nachega Jean B , Sam-Agudu Nadia A , Mofenson Lynne M , Schechter Mauro , Mellors John W 
Published: January 2018

Abstract
Although significant progress has been made, the latest data from low- and middle-income countries show substantial gaps in reaching the third “90%” (viral suppression) of the UNAIDS 90-90-90 goals, especially among vulnerable and key populations. This article discusses critical gaps and promising, evidence-based solutions. There is no simple and/or single approach to achieve the last 90%. This will require multifaceted, scalable strategies that engage people living with human immunodeficiency virus, motivate long-term treatment adherence, and are community-entrenched and ‑supported, cost-effective, and tailored to a wide range of global communities.
Branched Holomorphic Cartan Geometries and Calabi–Yau Manifolds
Authors: Biswas Indranil , Dumitrescu Sorin 
Published: January 2018

Abstract
We introduce the concept of a branched holomorphic Cartan geometry. It generalizes to higher dimension the definition of branched (flat) complex projective structure on a Riemann surface introduced by Mandelbaum [25]. This new framework is much more flexible than that of the usual holomorphic Cartan geometries. We show that all compact complex projective manifolds admit a branched flat holomorphic projective structure. We also give an example of a non-flat branched holomorphic normal projective structure on a compact complex surface. It is known that no compact complex surface admits such a structure with empty branching locus. We prove that non-projective compact simply connected Kähler Calabi–Yau manifolds do not admit any branched holomorphic projective structure. The key ingredient of its proof is the following result of independent interest: if E is a holomorphic vector bundle over a compact simply connected Kähler Calabi–Yau manifold and E admits a holomorphic connection, then E is a trivial holomorphic vector bundle and any holomorphic connection on E is trivial.
The Completed Finite Period Map and Galois Theory of Supercongruences
Authors: Rosen Julian 
Published: January 2018

AbstractA period is a complex number arising as the integral of a rational function with algebraic number coefficients over a region cut out by finitely many inequalities between polynomials with rational coefficients. Although periods are typically transcendental numbers, there is a conjectural Galois theory of periods coming from the theory of motives. This paper formalizes an analogy between a class of periods called multiple zeta values and congruences for rational numbers modulo prime powers (called supercongruences). We construct an analog of the motivic period map in the setting of supercongruences and use it to define a Galois theory of supercongruences. We describe an algorithm using our period map to find and prove supercongruences, and we provide software implementing the algorithm.
Radially Distributed Values and Normal Families
Authors: Bergweiler Walter , Eremenko Alexandre 
Published: January 2018

AbstractLet L0 and L1 be two distinct rays emanating from the origin and let ${\mathcal{F}}$ be the family of all functions holomorphic in the unit disk ${\mathbb{D}}$ for which all zeros lie on L0 while all 1-points lie on L1. It is shown that ${\mathcal{F}}$ is normal in ${\mathbb{D}}\backslash \{0\}$. The case where L0 is the positive real axis and L1 is the negative real axis is studied in more detail.
Oxidative burst and Dectin-1-triggered phagocytosis affected by norepinephrine and endocannabinoids: implications for fungal clearance under stress
Authors: Buchheim Judith-Irina , Hoskyns Spencer , Moser Dominique , Han Bing , Deindl Elisabeth , Hörl Marion , Biere Katharina , Feuerecker Matthias , Schelling Gustav , Choukèr Alexander 
Published: January 2018

AbstractA prolonged stress burden is known to hamper the efficiency of both the innate and the adaptive immune systems and to attenuate the stress responses by the catecholaminergic and endocannabinoid (EC) systems. Key mechanisms of innate immunity are the eradication of pathogens through phagocytosis and the respiratory burst. We tested the concentration-dependent, spontaneous and stimulated (via TNFα and N-formylmethionine-leucyl-phenylalanine) release of reactive oxygen species (ROS) by human polymorphonuclear leukocytes (PMNs) in vitro in response to norepinephrine (NE) and AM1241, a pharmacological ligand for the EC receptor CB2. We evaluated phagocytosis of Dectin-1 ligating zymosan particles and tested the cytokine response against Candida antigen in an in vitro cytokine release assay. Increasing concentrations of NE did not affect phagocytosis, yet stimulated ROS release was attenuated gradually reaching maximum suppression at 500 nM. Adrenergic receptor (AR) mechanisms using non-AR-selective (labetalol) as well as specific α-(prazosin) and β-(propranolol) receptor antagonists were tested. Results show that only labetalol and propranolol were able to recuperate cytotoxicity in the presence of NE, evidencing a β-receptor-mediated effect. The CB2 agonist, AM1241, inhibited phagocytosis at 10 µM and spontaneous peroxide release by PMNs. Use of the inverse CB2 receptor agonist SR144528 led to partial recuperation of ROS production, confirming the functional role of CB2. Additionally, AM1241 delayed early activation of monocytes and induced suppression of IL-2 and IL-6 levels in response to Candida via lower activity of mammalian target of rapamycin (mTOR). These findings provide new insights into key mechanisms of innate immunity under stressful conditions where ligands to the sympatho-adrenergic and EC system are released.
Mutation Signatures Including APOBEC in Cancer Cell Lines
Authors: Jarvis Matthew C , Ebrahimi Diako , Temiz Nuri A , Harris Reuben S 
Published: January 2018

Abstract

Background:
Multiple endogenous and exogenous sources of DNA damage contribute to the overall mutation burden in cancer, with distinct and overlapping combinations contributing to each cancer type. Many mutation sources result in characteristic mutation signatures, which can be deduced from tumor genomic DNA sequences. Examples include spontaneous hydrolytic deamination of methyl-cytosine bases in CG motifs (AGEING signature) and C-to-T and C-to-G mutations in 5'-TC(A/T) motifs (APOBEC signature).

Methods:
The deconstructSigs R package was used to analyze single-base substitution mutation signatures in more than 1000 cancer cell lines. Two additional approaches were used to analyze the APOBEC mutation signature.

Results:
Most cell lines show evidence for multiple mutation signatures. For instance, the AGEING signature, which is the largest source of mutation in most primary tumors, predominates in the majority of cancer cell lines. The APOBEC mutation signature is enriched in cancer cell lines from breast, lung, head/neck, bladder, and cervical cancers, where this signature also comprises a large fraction of all mutations.

Conclusions:
The single-base substitution mutation signatures of cancer cell lines often reflect those of the original tumors from which they are derived. Cancer cell lines with enrichments for distinct mutation signatures such as APOBEC have the potential to become model systems for fundamental research on the underlying mechanisms and for advancing clinical strategies to exploit these processes.
Phylogenetic analysis of Histoplasma capsulatum var duboisii in baboons from archived formalin-fixed, paraffin embedded tissues
Authors: Hensel M , Hoffmann A Rodrigues , Gonzales M , Owston M A , Dick E J 
Published: January 2018

AbstractHistoplasma capsulatum var. duboisii (Hcd) infections have been well documented to cause chronic granulomatous disease, mainly involving the skin of baboons and humans in African countries primarily. This retrospective study classified the subspecies of Histoplasma and developed a phylogenetic tree utilizing DNA sequences extracted from formalin-fixed, paraffin embedded (FFPE) tissues from 9 baboons from a research colony in Texas histologically diagnosed with Hcd. Based on sequence analysis of ITS-2, Tub-1, and ARF, Hcd isolated from the archived samples closely aligns with the African clade and has 88% sequence homology with a sample isolated from an individual in Senegal.
Explosions of Thorne–Żytkow objects
Authors: Moriya Takashi J 
Published: January 2018

Abstract
We propose that massive Thorne–Żytkow objects can explode. A Thorne–Żytkow object is a theoretically predicted star that has a neutron core. When nuclear reactions supporting a massive Thorne–Żytkow object terminate, a strong accretion occurs towards the central neutron core. The accretion rate is large enough to sustain a super-Eddington accretion towards the neutron core. The neutron core may collapse to a black hole after a while. A strong large-scale outflow or a jet can be launched from the super-Eddington accretion disc and the collapsing Thorne–Żytkow object can be turned into an explosion. The ejecta have about 10 M⊙ but the explosion energy depends on when the accretion is suppressed. We presume that the explosion energy could be as low as ∼1047 erg and such a low-energy explosion could be observed like a failed supernova. The maximum possible explosion energy is ∼1052 erg and such a high-energy explosion could be observed as an energetic Type II supernova or a superluminous supernova. Explosions of Thorne–Żytkow objects may provide a new path to spread lithium and other heavy elements produced through the irp process such as molybdenum in the Universe.
Tidal double detonation: a new mechanism for the thermonuclear explosion of a white dwarf induced by a tidal disruption event
Authors: Tanikawa Ataru 
Published: January 2018

Abstract
We suggest tidal double detonation as a new mechanism for the thermonuclear explosion of a white dwarf (WD) induced by a tidal disruption event (TDE). Tidal detonation is also a WD explosion induced by a TDE. In this case, helium (He) and carbon–oxygen (CO) detonation waves incinerate He WDs and CO WDs, respectively. On the other hand, for tidal double detonation, He detonation is first excited in the He shell of a CO WD, which then drives CO detonation in the CO core. We name this mechanism after the double detonation scenario in the context of type Ia supernovae. In this paper, by performing numerical simulations for CO WDs of mass 0.60 M⊙ with and without a He shell, we show that tidal double detonation occurs in the shallower encounter of a CO WD with an intermediate-mass black hole (IMBH) compared to simple tidal detonation. We expect tidal double detonation will increase the possibility of the occurrence of WD TDEs, which can help us to understand IMBHs.
Faraday rotation signatures of fluctuation dynamos in young galaxies
Authors: Sur Sharanya , Bhat Pallavi , Subramanian Kandaswamy 
Published: January 2018

Abstract
Observations of Faraday rotation through high-redshift galaxies have revealed that they host coherent magnetic fields that are of comparable strengths to those observed in nearby galaxies. These fields could be generated by fluctuation dynamos. We use idealized numerical simulations of such dynamos in forced compressible turbulence up to rms Mach number of 2.4 to probe the resulting rotation measure (RM) and the degree of coherence of the magnetic field. We obtain rms values of RM at dynamo saturation of the order of 45–55 per cent of the value expected in a model where fields are assumed to be coherent on the forcing scale of turbulence. We show that the dominant contribution to the RM in subsonic and transonic cases comes from the general sea of volume filling fields, rather than from the rarer structures. However, in the supersonic case, strong field regions as well as moderately overdense regions contribute significantly. Our results can account for the observed RMs in young galaxies.
Remodeling of the Feeding Arterial System After Surgery for Resection of Brain Arteriovenous Malformations: An Observational Study
Authors: Morgan Michael Kerin , Guilfoyle Mathew , Kirollos Ramez , Heller Gillian Z 
Published: January 2018

Abstract

BACKGROUND
Avoiding the risk of postoperative hemorrhage after brain arteriovenous malformation (AVM) resection involves aggressive blood pressure control. Remodeling of the feeding arterial system is critical in reducing this risk.

OBJECTIVE
To investigate factors predicting time to return to normal on digital subtraction angiography (DSA) after AVM resection.

METHODS
For AVM in which the largest feeding artery (FA) on DSA was in the anterior circulation, the preoperative and postoperative diameter of the FA were compared with the diameter of the internal carotid artery (IC) immediately proximal to the posterior communicating artery. The preoperative FA/IC ratio (FA/IC preAVM) was compared with the first postoperative FA/IC ratio (FA/IC postAVM). Normal FA/IC ratio (FA/IC normal) was established from matched arteries in the contralateral hemisphere to the AVM.

RESULTS
Eighty-six patients were analyzed for postoperative DSA performed a median 4 d after resection. From the interval-censored proportional hazards regression analysis, FA/IC preAVM (hazard ratio of 0.0006; 95% confidence interval: 0.00-0.21; P = .013) and maximum AVM diameter (hazard ratio of 0.47; 95% confidence interval: 0.23-0.95; P = .036) were significant in time to return to normal. These 2 factors were poorly correlated with each other (r = 0.41). AVMs with FA/IC preAVMs <0.57 combined with a diameter <3.0 cm normalize within 7 d in more than 50% of cases. Any other combination of ratio and size has fewer than 20% normalizing within 7 d (log rank P < .001).

CONCLUSION
FA/IC preAVM and AVM size are both important in predicting the time taken for return to normal feeding arterial system on DSA after AVM resection.
Dimensional crossover of heat conduction in amorphous polyimide nanofibers
Authors: Dong Lan , Xi Qing , Chen Dongsheng , Guo Jie , Nakayama Tsuneyoshi , Li Yunyun , Liang Ziqi , Zhou Jun , Xu Xiangfan , Li Baowen 
Published: January 2018

ABSTRACTThe mechanism of thermal conductivity in amorphous polymers, especially polymer fibers, is unclear in comparison with that in inorganic materials. Here, we report the observation of a crossover of heat conduction behavior from three dimensions to quasi-one dimension in polyimide nanofibers at a given temperature. A theoretical model based on the random walk theory has been proposed to quantitatively describe the interplay between the inter-chain hopping and the intra-chain hopping in nanofibers. This model explains well the diameter dependence of thermal conductivity and also speculates on the upper limit of thermal conductivity of amorphous polymers in the quasi-1D limit.