bluuebunny/crossref_metadata_2025_split huggingface dataset:
Uncovering the Repertoire of Endogenous Flaviviral Elements in Aedes Mosquito Genomes
Authors: Suzuki Yasutsugu , Frangeul Lionel , Dickson Laura B. , Blanc Hervé , Verdier Yann , Vinh Joelle , Lambrechts Louis , Saleh Maria-Carla 
Published: May 2017

ABSTRACT

Endogenous viral elements derived from nonretroviral RNA viruses have been described in various animal genomes. Whether they have a biological function, such as host immune protection against related viruses, is a field of intense study. Here, we investigated the repertoire of endogenous flaviviral elements (EFVEs) in
Aedes
mosquitoes, the vectors of arboviruses such as dengue and chikungunya viruses. Previous studies identified three EFVEs from
Aedes albopictus
cell lines and one from
Aedes aegypti
cell lines. However, an in-depth characterization of EFVEs in wild-type mosquito populations and individual mosquitoes
in vivo
has not been performed. We detected the full-length DNA sequence of the previously described EFVEs and their respective transcripts in several
A. albopictus
and
A. aegypti
populations from geographically distinct areas. However, EFVE-derived proteins were not detected by mass spectrometry. Using deep sequencing, we detected the production of PIWI-interacting RNA-like small RNAs, in an antisense orientation, targeting the EFVEs and their flanking regions
in vivo
. The EFVEs were integrated in repetitive regions of the mosquito genomes, and their flanking sequences varied among mosquito populations. We bioinformatically predicted several new EFVEs from a Vietnamese
A. albopictus
population and observed variation in the occurrence of those elements among mosquitoes. Phylogenetic analysis of an
A. aegypti
EFVE suggested that it integrated prior to the global expansion of the species and subsequently diverged among and within populations. The findings of this study together reveal the substantial structural and nucleotide diversity of flaviviral integrations in
Aedes
genomes. Unraveling this diversity will help to elucidate the potential biological function of these EFVEs.

IMPORTANCE
Endogenous viral elements (EVEs) are whole or partial viral sequences integrated in host genomes. Interestingly, some EVEs have important functions for host fitness and antiviral defense. Because mosquitoes also have EVEs in their genomes, characterizing these EVEs is a prerequisite for their potential use to manipulate the mosquito antiviral response. In the study described here, we focused on EVEs related to the
Flavivirus
genus, to which dengue and Zika viruses belong, in individual
Aedes
mosquitoes from geographically distinct areas. We show the existence
in vivo
of flaviviral EVEs previously identified in mosquito cell lines, and we detected new ones. We show that EVEs have evolved differently in each mosquito population. They produce transcripts and small RNAs but not proteins, suggesting a function at the RNA level. Our study uncovers the diverse repertoire of flaviviral EVEs in
Aedes
mosquito populations and contributes to an understanding of their role in the host antiviral system.
Interactions between HIV-1 Gag and Viral RNA Genome Enhance Virion Assembly
Authors: Dilley Kari A. , Nikolaitchik Olga A. , Galli Andrea , Burdick Ryan C. , Levine Louis , Li Kelvin , Rein Alan , Pathak Vinay K. , Hu Wei-Shau 
Published: May 2017

ABSTRACT
Most HIV-1 virions contain two copies of full-length viral RNA, indicating that genome packaging is efficient and tightly regulated. However, the structural protein Gag is the only component required for the assembly of noninfectious viruslike particles, and the viral RNA is dispensable in this process. The mechanism that allows HIV-1 to achieve such high efficiency of genome packaging when a packageable viral RNA is not required for virus assembly is currently unknown. In this report, we examined the role of HIV-1 RNA in virus assembly and found that packageable HIV-1 RNA enhances particle production when Gag is expressed at levels similar to those in cells containing one provirus. However, such enhancement is diminished when Gag is overexpressed, suggesting that the effects of viral RNA can be replaced by increased Gag concentration in cells. We also showed that the specific interactions between Gag and viral RNA are required for the enhancement of particle production. Taken together, these studies are consistent with our previous hypothesis that specific dimeric viral RNA-Gag interactions are the nucleation event of infectious virion assembly, ensuring that one RNA dimer is packaged into each nascent virion. These studies shed light on the mechanism by which HIV-1 achieves efficient genome packaging during virus assembly.

IMPORTANCE
Retrovirus assembly is a well-choreographed event, during which many viral and cellular components come together to generate infectious virions. The viral RNA genome carries the genetic information to new host cells, providing instructions to generate new virions, and therefore is essential for virion infectivity. In this report, we show that the specific interaction of the viral RNA genome with the structural protein Gag facilitates virion assembly and particle production. These findings resolve the conundrum that HIV-1 RNA is selectively packaged into virions with high efficiency despite being dispensable for virion assembly. Understanding the mechanism used by HIV-1 to ensure genome packaging provides significant insights into viral assembly and replication.
Superficial ideals for monomial ideals
Authors: Rajaee Saeed , Nasernejad Mehrdad , Al-Ayyoub Ibrahim 
Published: May 2017

Let [Formula: see text] and [Formula: see text] be two ideals in a commutative Noetherian ring [Formula: see text]. We say that [Formula: see text] is a superficial ideal for [Formula: see text] if the following conditions are satisfied: (i) [Formula: see text], where [Formula: see text] denotes a minimal set of generators of an ideal [Formula: see text]. (ii) [Formula: see text] for all positive integers [Formula: see text]. In this paper, by using some monomial operators, we first introduce several methods for constructing new ideals which have superficial ideals. In the sequel, we present some examples of monomial ideals which have superficial ideals. Next, we discuss on the relation between superficiality and normality. Finally, we explore the relation between normally torsion-freeness and superficiality.
Geomechanical characterization of mud volcanoes using P-wave velocity datasets
Authors: Gulmammadov Rashad , Covey-Crump Stephen , Huuse Mads 
Published: May 2017

Abstract
Mud volcanoes occur in many petroliferous basins and are associated with significant drilling hazards. To illustrate the type of information that can be extracted from limited petrophysical datasets in such geomechanically complex settings, we use P-wave velocity data to calculate the mechanical properties and stresses on a two-dimensional vertical section across a mud volcano in the Azeri-Chirag-Guneshly field, South Caspian Basin. We find that: (1) the values of the properties and stresses calculated in this way have realistic magnitudes; (2) the calculated pore fluid pressures show spatial variations around the mud volcano that potentially highlight areas of fluid recharging after the most recent eruption; and (3) the information obtained is sufficient to provide helpful indications of the width of the drilling window. Although calculations of this kind may be readily improved with more sophisticated petrophysical datasets, the simplicity of this approach makes it attractive for reconnaissance surveys designed to identify targets worthy of further investigation in developing our understanding of mud volcano geomechanics, or which could be used to help formulate drilling strategies.
The edge of failure: critical stress overpressure states in different tectonic regimes
Authors: Sibson Richard H. 
Published: May 2017

Abstract

Earth's seismogenic crust is partitioned into the three Andersonian stress domains critically organized to the edge of failure both along plate boundaries and within plate interiors. Brittle/frictional failure in rocks (the formation and reactivation of faults and fractures) may be induced by two principal drivers: increasing differential stress (σ
1
–σ
3
) and/or pore fluid pressure,
P
f
, defined relative to vertical stress by λ
v
=
P
f
/σ
v
. Borehole measurements suggest the presence of hydrostatic-Byerlee conditions (the stress governed by the frictional strength of optimally oriented faults with Byerlee friction (0.6<μ
s
<0.85) under hydrostatic fluid pressure), sometimes postulated as the standard state for fractured seismogenic crust with a bulk permeability too high to allow fluid overpressuring. However, especially in areas of crust undergoing shortening and fluid release under compression, pore fluids are likely to be overpressured above the hydrostatic pressure (i.e. λ
v
>0.4) in the lower seismogenic zone (
c. T
>200°C), where hydrothermal circulation and cementation reduces fracture permeability. In such regions, critical stress overpressure states prevail with differential stress inversely related to the degree of fluid overpressuring. Failure criteria on plots of (σ
1
–σ
3
) v. λ
v
constructed for particular depths can be used to explore critical stress overpressure states, loading paths to failure and potential mineralizing scenarios in different settings.
Dyke emplacement and crustal structure within a continental large igneous province, northern Barents Sea
Authors: Minakov Alexander , Yarushina Viktoriya , Faleide Jan Inge , Krupnova Nataliya , Sakoulina Tamara , Dergunov Nikolay , Glebovsky Vladimir 
Published: May 2017

Abstract
We perform an integrated analysis of magnetic anomalies, multichannel seismic and wide-angle seismic data across an Early Cretaceous continental large igneous province in the northern Barents Sea region. Our data show that the high-frequency and high-amplitude magnetic anomalies in this region are spatially correlated with dykes and sills observed onshore. The dykes are grouped into two conjugate swarms striking oblique to the northern Barents Sea passive margin in the regions of eastern Svalbard and Franz Josef Land, respectively. The multichannel seismic data east of Svalbard and south of Franz Josef Land indicate the presence of sills at different stratigraphic levels. The most abundant population of sills is observed in the Triassic successions of the East Barents Sea Basin. We observe near-vertical seismic column-like anomalies that cut across the entire sedimentary cover. We interpret these structures as magmatic feeder channels or dykes. In addition, the compressional seismic velocity model locally indicates near-vertical, positive finger-shaped velocity anomalies (10–15 km wide) that extend to mid-crustal depths (15–20 km) and possibly deeper. The crustal structure does not include magmatic underplating and shows no regional crustal thinning, suggesting a localized (dyking, channelized flow) rather than a pervasive mode of magma emplacement. We suggest that most of the crustal extension was taken up by brittle–plastic dilatation in shear bands. We interpret the geometry of dykes in the horizontal plane in terms of the palaeo-stress regime using a model of a thick elastoplastic plate containing a circular hole (at the plume location) and subject to combined pure shear and pressure loads. The geometry of dykes in the northern Barents Sea and Arctic Canada can be predicted by the pattern of dilatant plastic shear bands obtained in our numerical experiments assuming boundary conditions consistent with a combination of extension in the Amerasia Basin sub-parallel to the northern Barents Sea margin and a mild compression nearly orthogonal to the margin. The approach has implications for palaeo-stress analysis using the geometry of dyke swarms.
Effective Regression Test Case Selection
Authors: Kazmi Rafaqut , Jawawi Dayang N. A. , Mohamad Radziah , Ghani Imran 
Published: May 2017

Regression test case selection techniques attempt to increase the testing effectiveness based on the measurement capabilities, such as cost, coverage, and fault detection. This systematic literature review presents state-of-the-art research in effective regression test case selection techniques. We examined 47 empirical studies published between 2007 and 2015. The selected studies are categorized according to the selection procedure, empirical study design, and adequacy criteria with respect to their effectiveness measurement capability and methods used to measure the validity of these results.
The results showed that mining and learning-based regression test case selection was reported in 39% of the studies, unit level testing was reported in 18% of the studies, and object-oriented environment (Java) was used in 26% of the studies. Structural faults, the most common target, was used in 55% of the studies. Overall, only 39% of the studies conducted followed experimental guidelines and are reproducible.
There are 7 different cost measures, 13 different coverage types, and 5 fault-detection metrics reported in these studies. It is also observed that 70% of the studies being analyzed used cost as the effectiveness measure compared to 31% that used fault-detection capability and 16% that used coverage.
Postexercise cold water immersion modulates skeletal muscle PGC-1α mRNA expression in immersed and nonimmersed limbs: evidence of systemic regulation
Authors: Allan Robert , Sharples Adam P. , Close Graeme L. , Drust Barry , Shepherd Sam O. , Dutton John , Morton James P. , Gregson Warren 
Published: May 2017

Mechanisms mediating postexercise cold-induced increases in PGC-1α gene expression in human skeletal muscle are yet to be fully elucidated but may involve local cooling effects on AMPK and p38 MAPK-related signaling and/or increased systemic β-adrenergic stimulation. Therefore, we aimed to examine whether postexercise cold water immersion enhancement of PGC-1α mRNA is mediated through local or systemic mechanisms. Ten subjects completed acute cycling (8 × 5 min at ~80% peak power output) followed by seated-rest (CON) or single-leg cold water immersion (CWI; 10 min, 8°C). Muscle biopsies were obtained preexercise, postexercise, and 3 h postexercise from a single limb in the CON condition but from both limbs in CWI [thereby providing tissue from a CWI and nonimmersed limb (NOT)]. Muscle temperature decreased up to 2 h postexercise following CWI (−5°C) in the immersed limb, with lesser changes observed in CON and NOT (−3°C, P < 0.05). No differences between limbs were observed in p38 MAPK phosphorylation at any time point ( P < 0.05), whereas a significant interaction effect was present for AMPK phosphorylation ( P = 0.031). Exercise (CON) increased gene expression of PGC-1α 3 h postexercise (~5-fold, P < 0.001). CWI augmented PGC-1α expression above CON in both the immersed (CWI; ~9-fold, P = 0.003) and NOT limbs (~12-fold, P = 0.001). Plasma normetanephrine concentration was higher in CWI vs. CON immediately postimmersion (860 vs. 665 pmol/l, P = 0.034). We report for the first time that local cooling of the immersed limb evokes transcriptional control of PGC-1α in the nonimmersed limb, suggesting increased systemic β-adrenergic activation of AMPK may mediate, in part, postexercise cold induction of PGC-1α mRNA. NEW & NOTEWORTHY We report for the first time that postexercise cold water immersion of one limb also enhances PGC-1α expression in a contralateral, nonimmersed limb. We suggest that increased systemic β-adrenergic stimulation, and not localized cooling per se, exerts regulatory effects on local signaling cascades, thereby modulating PGC-1α expression. Therefore, these data have important implications for research designs that adopt contralateral, nonimmersed limbs as a control condition while also increasing our understanding of the potential mechanisms underpinning cold-mediated PGC-1α responses.
ETV1-Positive Cells Give Rise to BRAFV600E-Mutant Gastrointestinal Stromal Tumors
Authors: Ran Leili , Murphy Devan , Sher Jessica , Cao Zhen , Wang Shangqian , Walczak Edward , Guan Youxin , Xie Yuanyuan , Shukla Shipra , Zhan Yu , Antonescu Cristina R. , Chen Yu , Chi Ping 
Published: May 2017

Abstract
Gastrointestinal stromal tumor (GIST) is the most common subtype of sarcoma. Despite clinical advances in the treatment of KIT/PDGFRA–mutant GIST, similar progress against KIT/PDGFRA wild-type GIST, including mutant BRAF-driven tumors, has been limited by a lack of model systems. ETV1 is a master regulator in the intestinal cells of Cajal (ICC), thought to be the cells of origin of GIST. Here, we present a model in which the ETV1 promoter is used to specifically and inducibly drive Cre recombinase in ICC as a strategy to study GIST pathogenesis. Using a conditional allele for BrafV600E, a mutation observed in clinical cases of GIST, we observed that BrafV600E activation was sufficient to drive ICC hyperplasia but not GIST tumorigenesis. In contrast, combining BrafV600E activation with Trp53 loss was sufficient to drive both ICC hyperplasia and formation of multifocal GIST-like tumors in the mouse gastrointestinal tract with 100% penetrance. This mouse model of sporadic GIST model was amenable to therapeutic intervention, and it recapitulated clinical responses to RAF inhibition seen in human GIST. Our work offers a useful in vivo model of human sporadic forms of BRAF-mutant GIST to help unravel its pathogenesis and therapeutic response to novel experimental agents. Cancer Res; 77(14); 3758–65. ©2017 AACR.
Utility of Genomic Assessment of Blood-Derived Circulating Tumor DNA (ctDNA) in Patients with Advanced Lung Adenocarcinoma
Authors: Schwaederlé Maria C. , Patel Sandip P. , Husain Hatim , Ikeda Megumi , Lanman Richard B. , Banks Kimberly C. , Talasaz AmirAli , Bazhenova Lyudmila , Kurzrock Razelle 
Published: May 2017

Abstract
Purpose: Genomic alterations in blood-derived circulating tumor DNA (ctDNA) from patients with non–small cell lung adenocarcinoma (NSCLC) were ascertained and correlated with clinical characteristics and therapeutic outcomes.
Experimental Design: Comprehensive plasma ctDNA testing was performed in 88 consecutive patients; 34 also had tissue next-generation sequencing; 29, other forms of genotyping; and 25 (28.4%) had no tissue molecular tests because of inadequate tissue or biopsy contraindications.
Results: Seventy-two patients (82%) had ≥1 ctDNA alteration(s); among these, 75% carried alteration(s) potentially actionable by FDA-approved (61.1%) or experimental drug(s) in clinical trials (additional 13.9%). The most frequent alterations were in the TP53 (44.3% of patients), EGFR (27.3%), MET (14.8%), KRAS (13.6%), and ALK (6.8%) genes. The concordance rate for EGFR alterations was 80.8% (100% vs. 61.5%; ≤1 vs. &gt;1 month between ctDNA and tissue tests; P = 0.04) for patients with any detectable ctDNA alterations. Twenty-five patients (28.4%) received therapy matching ≥1 ctDNA alteration(s); 72.3% (N = 16/22) of the evaluable matched patients achieved stable disease ≥6 months (SD) or partial response (PR). Five patients with ctDNA-detected EGFR T790M were subsequently treated with a third generation EGFR inhibitor; all five achieved SD ≥ 6 months/PR. Patients with ≥1 alteration with ≥5% variant allele fraction (vs. &lt; 5%) had a significantly shorter median survival (P = 0.012).
Conclusions: ctDNA analysis detected alterations in the majority of patients, with potentially targetable aberrations found at expected frequencies. Therapy matched to ctDNA alterations demonstrated appreciable therapeutic efficacy, suggesting clinical utility that warrants future prospective studies. Clin Cancer Res; 23(17); 5101–11. ©2017 AACR.
Modeling the Cellular Response of Lung Cancer to Radiation Therapy for a Broad Range of Fractionation Schedules
Authors: Jeong Jeho , Oh Jung Hun , Sonke Jan-Jakob , Belderbos Jose , Bradley Jeffrey D. , Fontanella Andrew N. , Rao Shyam S. , Deasy Joseph O. 
Published: May 2017

Abstract
Purpose: To demonstrate that a mathematical model can be used to quantitatively understand tumor cellular dynamics during a course of radiotherapy and to predict the likelihood of local control as a function of dose and treatment fractions.
Experimental Design: We model outcomes for early-stage, localized non–small cell lung cancer (NSCLC), by fitting a mechanistic, cellular dynamics-based tumor control probability that assumes a constant local supply of oxygen and glucose. In addition to standard radiobiological effects such as repair of sub-lethal damage and the impact of hypoxia, we also accounted for proliferation as well as radiosensitivity variability within the cell cycle. We applied the model to 36 published and two unpublished early-stage patient cohorts, totaling 2,701 patients.
Results: Precise likelihood best-fit values were derived for the radiobiological parameters: α [0.305 Gy−1; 95% confidence interval (CI), 0.120–0.365], the α/β ratio (2.80 Gy; 95% CI, 0.40–4.40), and the oxygen enhancement ratio (OER) value for intermediately hypoxic cells receiving glucose but not oxygen (1.70; 95% CI, 1.55–2.25). All fractionation groups are well fitted by a single dose–response curve with a high χ2 P value, indicating consistency with the fitted model. The analysis was further validated with an additional 23 patient cohorts (n = 1,628). The model indicates that hypofractionation regimens overcome hypoxia (and cell-cycle radiosensitivity variations) by the sheer impact of high doses per fraction, whereas lower dose-per-fraction regimens allow for reoxygenation and corresponding sensitization, but lose effectiveness for prolonged treatments due to proliferation.
Conclusions: This proposed mechanistic tumor-response model can accurately predict overtreatment or undertreatment for various treatment regimens. Clin Cancer Res; 23(18); 5469–79. ©2017 AACR.
Aberrant Methylation-Mediated Silencing of lncRNA MEG3 Functions as a ceRNA in Esophageal Cancer
Authors: Dong Zhiming , Zhang Aili , Liu Shengnan , Lu Fan , Guo Yanli , Zhang Guoqiang , Xu Fenglou , Shi Yabin , Shen Supeng , Liang Jia , Guo Wei 
Published: May 2017

Abstract
Maternally expressed gene 3 (MEG3), a long non-coding RNA (lncRNA), has tumor-suppressor properties and its expression is lost in several human tumors. However, its biological role in esophageal squamous cell carcinoma (ESCC) tumorigenesis is poorly defined. The present study determined the role and methylation status of MEG3 in esophageal cancer cells and ESCC clinical specimens, and further observed the competing endogenous RNA (ceRNA) activity of MEG3 in the pathogenesis and development of ESCC. Significant downregulation of MEG3 was detected in esophageal cancer cells and ESCC tissues and the expression level of MEG3 was significantly increased in cancer cells after treated with the DNA methyltransferase inhibitor 5-Aza-dC. Upregulation of MEG3 led to the inhibition of proliferation and invasiveness of the cancer cells. The aberrant promoter hypermethylation of MEG3 indicates silencing of its expression. Furthermore, MEG3 acts as a ceRNA to regulate the expression of E-cadherin and FOXO1 by binding hsa-miR-9. Upregulation of miR-9 was detected in esophageal cancer cell lines and ESCC tissues, and miR-9 promoted esophageal cancer cell proliferation and invasion. Finally, downregulation and hypermethylation of MEG3 was associated with ESCC patients' survival.
Implications: MEG3 functions as a tumor-suppressive lncRNA and aberrant promoter hypermethylation is critical for MEG3 gene silencing in ESCC. In addition, MEG3 acts as a ceRNA to regulate expression of E-cadherin and FOXO1 by competitively binding miR-9 and may be used as a potential biomarker in predicting ESCC patients' progression and prognosis. Mol Cancer Res; 15(7); 800–10. ©2017 AACR.