bluuebunny/crossref_metadata_2025_split huggingface dataset:
Differential pH‐sensitive sensor with DC electrode‐offset compensation
Authors: Lee K.H. , Lee D. , Yoon J. , Kwon O. , Lee J. 
Published: December 2016

A pH‐sensitive sensor with a differential mode was developed to detect surface charges accumulated on the ion‐sensitive layer. The device accurately monitors the relative pH value using the modified instrumentation amplifier with the DC electrode‐offset compensation. The readout voltage is digitalised with the current‐starved ring oscillator. The sensor achieves the DC offset compensation of 22.5 dB and the oscillating pH sensitivity of 1.3 MHz/pH. The feasibility of the sensor is demonstrated to monitor the hydrogen ion concentration comparing the oscillation frequency at differential mode with that at single mode.
The brain parenchyma has a type I interferon response that can limit virus spread
Authors: Drokhlyansky Eugene , Göz Aytürk Didem , Soh Timothy K. , Chrenek Ryan , O’Loughlin Elaine , Madore Charlotte , Butovsky Oleg , Cepko Constance L. 
Published: December 2016

Significance
The brain parenchyma is considered to be “immune privileged” based upon differences between the innate and adaptive immune responses of the brain and those of the periphery. This work provides a clear demonstration of an innate immune response to direct infection by a virus, a response that is capable of limiting the spread of the virus along neuronal circuitry. The question of the brain parenchyma’s response to a viral infection has implications for the use of viruses as tools by neuroscientists, for vaccine development, and for potential clinical applications. Additionally, the approach used here provides a framework for further examination of the immunologic state of the brain as well as the mechanisms by which encephalitic viruses circumvent this response.
Innovations and challenges in detecting long read overlaps: an evaluation
of the state-of-the-art
Authors: Chu Justin , Mohamadi Hamid , Warren René L , Yang Chen , Birol Inanç 
Published: December 2016

Abstract
Identifying overlaps between error-prone long reads, specifically those from Oxford Nanopore Technologies (ONT) and Pacific Biosciences (PB), is essential for certain downstream applications, including error correction and de novo assembly. Though akin to the read-to-reference alignment problem, read-to-read overlap detection is a distinct problem that can benefit from specialized algorithms that perform efficiently and robustly on high error rate long reads. Here, we review the current state-of-the-art read-to-read overlap tools for error-prone long reads, including BLASR, DALIGNER, MHAP, GraphMap and Minimap. These specialized bioinformatics tools differ not just in their algorithmic designs and methodology, but also in their robustness of performance on a variety of datasets, time and memory efficiency and scalability. We highlight the algorithmic features of these tools, as well as their potential issues and biases when utilizing any particular method. To supplement our review of the algorithms, we benchmarked these tools, tracking their resource needs and computational performance, and assessed the specificity and precision of each. In the versions of the tools tested, we observed that Minimap is the most computationally efficient, specific and sensitive method on the ONT datasets tested; whereas GraphMap and DALIGNER are the most specific and sensitive methods on the tested PB datasets. The concepts surveyed may apply to future sequencing technologies, as scalability is becoming more relevant with increased sequencing throughput.
Supplementary information: Supplementary data are available at Bioinformatics online.
Mathematical constraints onFST: biallelic markers in arbitrarily many populations
Authors: Alcala Nicolas , Rosenberg Noah A 
Published: December 2016

ABSTRACTFSTis one of the most widely used statistics in population genetics. Recent mathematical studies have identified constraints onFSTthat challenge interpretations ofFSTas a measure with potential to range from 0 for genetically similar populations to 1 for divergent populations. We generalize results obtained for population pairs to arbitrarily many populations, characterizing the mathematical relationship betweenFST, the frequencyMof the more frequent allele at a polymorphic biallelic marker, and the number of subpopulationsK. We show that for fixedK,FSThas a peculiar constraint as a function ofM, with a maximum of 1 only ifM=i/Kfor integersiwith ⌈K/2⌉ ≤i≤K− 1. For fixedM, asKgrows large, the range ofFSTbecomes the full closed or half-open unit interval. For fixedK, however, someM< (K− 1)/Kalways exists at which the upper bound onFSTis constrained to be below. In each of three migration models—island, rectangular stepping-stone, and linear stepping-stone—we use coalescent simulations to show that under weak migration,FSTdepends strongly on the allele frequencyMwhenKis small, but not whenKis large. Finally, using data on human genetic variation, we employ our results to explain the generally smallerFSTvalues between pairs of continents relative to globalFSTvalues. We discuss implications for the interpretation and use ofFST.
The Bayesian-Laplacian Brain
Authors: Zeki Semir , Chén Oliver Y. 
Published: December 2016

AbstractWe outline what we believe could be an improvement in future discussions of the brain acting as a Bayesian-Laplacian system. We do so by distinguishing between two broad classes of priors on which the brain’s inferential systems operate: in one category are biological priors (β priors) and in the other artifactual ones (α priors). We argue thatβ priors, of which colour categories and faces are good examples, are inherited or acquired very rapidly after birth, are highly or relatively resistant to change through experience, and are common to all humans. The consequence is that the probability of posteriors generated fromβ priorshaving universal assent and agreement is high. By contrast, αpriors, of which man-made objects are examples, are acquired post-natally and modified at various stages throughout post-natal life; they are much more accommodating of, and hospitable to, new experiences. Consequently, posteriors generated from them are less likely to find universal assent. Taken together, in addition to the more limited capacity of experiment and experience to alter theβ priorscompared toα priors, another cardinal distinction between the two is that the probability of posteriors generated fromβ priorshaving universal agreement is greater than that forα priors. The two categories are not, however, always totally distinct and can merge into one another to varying extents, resulting in posteriors that draw upon both categories.
De novoIdentification of DNA Modifications Enabled by Genome-Guided Nanopore Signal Processing
Authors: Stoiber Marcus , Quick Joshua , Egan Rob , Eun Lee Ji , Celniker Susan , Neely Robert K. , Loman Nicholas , Pennacchio Len A , Brown James 
Published: December 2016

AbstractAdvances in nanopore sequencing technology have enabled investigation of the full catalogue of covalent DNA modifications. We present the first algorithm for the identification of modified nucleotides without the need for prior training data along with the open source software implementation,nanoraw.Nanorawaccurately assigns contiguous raw nanopore signal to genomic positions, enabling novel data visualization, and increasing power and accuracy for the discovery of covalently modified bases in native DNA. Ground truth case studies utilizing synthetically methylated DNA show the capacity to identify three distinct methylation marks, 4mC, 5mC, and 6mA, in seven distinct sequence contexts without any changes to the algorithm. We demonstrate quantitative reproducibility simultaneously identifying 5mC and 6mA in native E. coli across biological replicates processed in different labs. Finally we propose a pipeline for the comprehensive discovery of DNA modifications in any genome withouta prioriknowledge of their chemical identities.
An assessment of the Upper Succession and the related secondary reservoirs in the Welton Field, onshore UK
Authors: Steventon James , Bowman Mike 
Published: December 2016

Abstract
The Welton oil field has produced nearly 20 MMBO (million barrels of oil) since discovery in 1981. Now in post-plateau decline, there is increasing reliance on a series of secondary reservoirs. Production has been from a suite of stacked reservoirs deposited by large-scale prograding delta-plain systems of early Westphalian age. Whilst the bulk of production has been from the Basal Succession, a considerable upside is considered to exist in the less well-studied Upper Succession that comprises predominantly distributary channel and crevasse splay deposits which have produced in excess of 3 MMBO. These accumulations occur within the Deep Soft Rock, Deep Hard Rock and Tupton reservoirs.
This paper focuses on a sedimentological analysis of cored intervals, integrated with petrophysical logs and detailed production data to enable further recommendations to identify areas of undrained pay, along with identifying additional reservoir management activities that could optimize future offtake from the field. These reservoirs consist predominantly of very fine-grained sandstone, with permeability values rarely attaining 100 mD and average porosity values of 10–12%.
Recommendations include executing tracer communication tests and building a detailed field model, as well as a pilot water-injection scheme to increase production from some of Welton's secondary reservoirs.

Supplementary material:
A full set of detailed sedimentological logs for each of the cored wells in this study is available at
https://doi.org/10.6084/m9.figshare.c.3593984
miR-200b inhibits TNF-α-induced IL-8 secretion and tight junction disruption of intestinal epithelial cells in vitro
Authors: Shen Yujie , Zhou Min , Yan Junkai , Gong Zizhen , Xiao Yongtao , Zhang Cong , Du Peng , Chen Yingwei 
Published: December 2016

Inflammatory bowel diseases (IBDs) are chronic, inflammatory disorders of the gastrointestinal tract with unclear etiologies. Intestinal epithelial cells (IECs), containing crypt and villus enterocytes, occupy a critical position in the pathogenesis of IBDs and are a major producer of immunoregulatory cytokines and a key component of the intact epithelial barrier. Previously, we have reported that miR-200b is involved in the progression of IBDs and might maintain the integrity of the intestinal epithelial barrier via reducing the loss of enterocytes. In this study, we further investigated the impact of miR-200b on intestinal epithelial inflammation and tight junctions in two distinct differentiated states of Caco-2 cells after TNF-α treatment. We demonstrated that TNF-α-enhanced IL-8 expression was decreased by microRNA (miR)-200b in undifferentiated IECs. Simultaneously, miR-200b could alleviate TNF-α-induced tight junction (TJ) disruption in well-differentiated IECs by reducing the reduction in the transepithelial electrical resistance (TEER), inhibiting the increase in paracellular permeability, and preventing the morphological redistribution of the TJ proteins claudin 1 and ZO-1. The expression levels of the JNK/c-Jun/AP-1 and myosin light chain kinase (MLCK)/phosphorylated myosin light chain (p-MLC) pathways were attenuated in undifferentiated and differentiated enterocytes, respectively. Furthermore, a dual-luciferase reporter gene detection system provided direct evidence that c-Jun and MLCK were the specific targets of miR-200b. Collectively, our results highlighted that miR-200b played a positive role in IECs via suppressing intestinal epithelial IL-8 secretion and attenuating TJ damage in vitro, which suggested that miR-200b might be a promising strategy for IBD therapy.NEW & NOTEWORTHY This was the first time that the inhibitory role of miR-200b on intestinal epithelial inflammation and paracellular permeability has been reported. Moreover, we further divided the intestinal epithelial cells (IECs) into two differentiated conditions and investigated the distinct impacts of miR-200b. Finally, we put forward and proved that myosin light chain kinase (MLCK) was a novel target of miR-200b.
Neural Stem Cell–Based Anticancer Gene Therapy: A First-in-Human Study in Recurrent High-Grade Glioma Patients
Authors: Portnow Jana , Synold Timothy W. , Badie Behnam , Tirughana Revathiswari , Lacey Simon F. , D'Apuzzo Massimo , Metz Marianne Z. , Najbauer Joseph , Bedell Victoria , Vo Tien , Gutova Margarita , Frankel Paul , Chen Mike , Aboody Karen S. 
Published: December 2016

Abstract
Purpose: Human neural stem cells (NSC) are inherently tumor tropic, making them attractive drug delivery vehicles. Toward this goal, we retrovirally transduced an immortalized, clonal NSC line to stably express cytosine deaminase (HB1.F3.CD.C21; CD-NSCs), which converts the prodrug 5-fluorocytosine (5-FC) to 5-fluorouracil (5-FU).
Experimental Design: Recurrent high-grade glioma patients underwent intracranial administration of CD-NSCs during tumor resection or biopsy. Four days later, patients began taking oral 5-FC every 6 hours for 7 days. Study treatment was given only once. A standard 3 + 3 dose escalation schema was used to increase doses of CD-NSCs from 1 × 107 to 5 × 107 and 5-FC from 75 to 150 mg/kg/day. Intracerebral microdialysis was performed to measure brain levels of 5-FC and 5-FU. Serial blood samples were obtained to assess systemic drug concentrations as well as to perform immunologic correlative studies.
Results: Fifteen patients underwent study treatment. We saw no dose-limiting toxicity (DLT) due to the CD-NSCs. There was 1 DLT (grade 3 transaminitis) possibly related to 5-FC. We did not see development of anti-CD-NSC antibodies and did not detect CD-NSCs or replication-competent retrovirus in the systemic circulation. Intracerebral microdialysis revealed that CD-NSCs produced 5-FU locally in the brain in a 5-FC dose-dependent manner. Autopsy data indicate that CD-NSCs migrated to distant tumor sites and were nontumorigenic.
Conclusions: Collectively, our results from this first-in-human study demonstrate initial safety and proof of concept regarding the ability of NSCs to target brain tumors and locally produce chemotherapy. Clin Cancer Res; 23(12); 2951–60. ©2016 AACR.
Combination Epigenetic Therapy in Advanced Breast Cancer with 5-Azacitidine and Entinostat: A Phase II National Cancer Institute/Stand Up to Cancer Study
Authors: Connolly Roisin M. , Li Huili , Jankowitz Rachel C. , Zhang Zhe , Rudek Michelle A. , Jeter Stacie C. , Slater Shannon A. , Powers Penny , Wolff Antonio C. , Fetting John H. , Brufsky Adam , Piekarz Richard , Ahuja Nita , Laird Peter W. , Shen Hui , Weisenberger Daniel J. , Cope Leslie , Herman James G. , Somlo George , Garcia Agustin A. , Jones Peter A. , Baylin Stephen B. , Davidson Nancy E. , Zahnow Cynthia A. , Stearns Vered 
Published: December 2016

AbstractPurpose: In breast cancer models, combination epigenetic therapy with a DNA methyltransferase inhibitor and a histone deacetylase inhibitor led to reexpression of genes encoding important therapeutic targets, including the estrogen receptor (ER). We conducted a multicenter phase II study of 5-azacitidine and entinostat in women with advanced hormone-resistant or triple-negative breast cancer (TNBC).Experimental Design: Patients received 5-azacitidine 40 mg/m2 (days 1–5, 8–10) and entinostat 7 mg (days 3, 10) on a 28-day cycle. Continuation of epigenetic therapy was offered with the addition of endocrine therapy at the time of progression [optional continuation (OC) phase]. Primary endpoint was objective response rate (ORR) in each cohort. We hypothesized that ORR would be ≥20% against null of 5% using Simon two-stage design. At least one response was required in 1 of 13 patients per cohort to continue accrual to 27 per cohort (type I error, 4%; power, 90%).Results: There was one partial response among 27 women with hormone-resistant disease (ORR = 4%; 95% CI, 0–19), and none in 13 women with TNBC. One additional partial response was observed in the OC phase in the hormone-resistant cohort (n = 12). Mandatory tumor samples were obtained pre- and posttreatment (58% paired) with either up- or downregulation of ER observed in approximately 50% of posttreatment biopsies in the hormone-resistant, but not TNBC cohort.Conclusions: Combination epigenetic therapy was well tolerated, but our primary endpoint was not met. OC phase results suggest that some women benefit from epigenetic therapy and/or reintroduction of endocrine therapy beyond progression, but further study is needed. Clin Cancer Res; 23(11); 2691–701. ©2016 AACR.
Dual HDAC and PI3K Inhibitor CUDC-907 Downregulates MYC and Suppresses Growth of MYC-dependent Cancers
Authors: Sun Kaiming , Atoyan Ruzanna , Borek Mylissa A. , Dellarocca Steven , Samson Maria Elena S. , Ma Anna W. , Xu Guang-Xin , Patterson Troy , Tuck David P. , Viner Jaye L. , Fattaey Ali , Wang Jing 
Published: December 2016

Abstract
Upregulation of MYC is a common driver event in human cancers, and some tumors depend on MYC to maintain transcriptional programs that promote cell growth and proliferation. Preclinical studies have suggested that individually targeting upstream regulators of MYC, such as histone deacetylases (HDAC) and phosphoinositide 3-kinases (PI3K), can reduce MYC protein levels and suppress the growth of MYC-driven cancers. Synergy between HDAC and PI3K inhibition in inducing cancer cell death has also been reported, but the involvement of MYC regulation is unclear. In this study, we demonstrated that HDAC and PI3K inhibition synergistically downregulates MYC protein levels and induces apoptosis in “double-hit” (DH) diffuse large B-cell lymphoma (DLBCL) cells. Furthermore, CUDC-907, a small-molecule dual-acting inhibitor of both class I and II HDACs and class I PI3Ks, effectively suppresses the growth and survival of MYC-altered or MYC-dependent cancer cells, such as DH DLBCL and BRD–NUT fusion-positive NUT midline carcinoma (NMC) cells, and MYC protein downregulation is an early event induced by CUDC-907 treatment. Consistently, the antitumor activity of CUDC-907 against multiple MYC-driven cancer types was also demonstrated in animal models, including DLBCL and NMC xenograft models, Myc transgenic tumor syngeneic models, and MYC-amplified solid tumor patient-derived xenograft (PDX) models. Our findings suggest that dual function HDAC and PI3K inhibitor CUDC-907 is an effective agent targeting MYC and thus may be developed as potential therapy for MYC-dependent cancers. Mol Cancer Ther; 16(2); 285–99. ©2016 AACR.
Imatinib Spares cKit-Expressing Prostate Neuroendocrine Tumors, whereas Kills Seminal Vesicle Epithelial–Stromal Tumors by Targeting PDGFR-β
Authors: Jachetti Elena , Rigoni Alice , Bongiovanni Lucia , Arioli Ivano , Botti Laura , Parenza Mariella , Cancila Valeria , Chiodoni Claudia , Festinese Fabrizio , Bellone Matteo , Tardanico Regina , Tripodo Claudio , Colombo Mario P. 
Published: December 2016

Abstract
Prostate cancer is a leading cause of cancer-related death in males worldwide. Indeed, advanced and metastatic disease characterized by androgen resistance and often associated with neuroendocrine (NE) differentiation remains incurable. Using the spontaneous prostate cancer TRAMP model, we have shown that mast cells (MCs) support in vivo the growth of prostate adenocarcinoma, whereas their genetic or pharmacologic targeting favors prostate NE cancer arousal. Aiming at simultaneously targeting prostate NE tumor cells and MCs, both expressing the cKit tyrosine kinase receptor, we have tested the therapeutic effect of imatinib in TRAMP mice. Imatinib-treated TRAMP mice experience a partial benefit against prostate adenocarcinoma, because of inhibition of supportive MCs. However, they show an unexpected outgrowth of prostate NE tumors, likely because of defective signaling pathway downstream of cKit receptor. Also unexpected but very effective was the inhibition of epithelial–stromal tumors of the seminal vesicles achieved by imatinib treatment. These tumors normally arise in the seminal vesicles of TRAMP mice, independently of the degree of prostatic glandular lesions, and resemble phyllodes tumors found in human prostate and seminal vesicles, and in breast. In both mice and in patients, these tumors are negative for cKit but express PDGFR-β, another tyrosine kinase receptor specifically inhibited by imatinib. Our results imply a possible detrimental effect of imatinib in prostate cancer patients but suggest a promising therapeutic application of imatinib in the treatment of recurrent or metastatic phyllodes tumors. Mol Cancer Ther; 16(2); 365–75. ©2016 AACR.
NOR-SASS (Norwegian Sonothrombolysis in Acute Stroke Study)
Authors: Nacu Aliona , Kvistad Christopher E. , Naess Halvor , Øygarden Halvor , Logallo Nicola , Assmus Jörg , Waje-Andreassen Ulrike , Kurz Kathinka D. , Neckelmann Gesche , Thomassen Lars 
Published: December 2016

Background and Purpose—
The NOR-SASS (Norwegian Sonothrombolysis in Acute Stroke Study) aimed to assess effect and safety of contrast-enhanced ultrasound treatment in an unselected acute ischemic stroke population.

Methods—
Patients treated with intravenous thrombolysis within 4.5 hours after symptom onset were randomized 1:1 to either contrast-enhanced sonothrombolysis (CEST) or sham CEST. A visible arterial occlusion on baseline computed tomography angiography was not a prerequisite for inclusion. Pulse-wave 2 MHz ultrasound was given for 1 hour and contrast (SonoVue) as an infusion for ≈30 minutes. Magnetic resonance imaging and angiography were performed after 24 to 36 hours. Primary study end points were neurological improvement at 24 hours defined as National Institutes of Health Stroke Scale score 0 or reduction of ≥4 National Institutes of Health Stroke Scale points compared with baseline National Institutes of Health Stroke Scale and favorable functional outcome at 90 days defined as modified Rankin scale score 0 to 1.

Results—
A total of 183 patients were randomly assigned to either CEST (93 patient) or sham CEST (90 patients). The rates of symptomatic intracerebral hemorrhage, asymptomatic intracerebral hemorrhage, or mortality were not increased in the CEST group. Neurological improvement at 24 hours and functional outcome at 90 days was similar in the 2 groups both in the intention-to-treat analysis and in the per-protocol analysis.

Conclusions—
CEST is safe among unselected ischemic stroke patients with or without a visible occlusion on computed tomography angiography and with varying grades of clinical severity. There was, however, statistically no significant clinical effect of sonothrombolysis in this prematurely stopped trial.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT01949961.
Weight-related peer-teasing moderates genetic and environmental risk and disordered eating: Twin study
Authors: Fairweather-Schmidt A. Kate , Wade Tracey D. 
Published: December 2016

BackgroundWeight-related peer-teasing is considered a potent prospective risk factor for development of disordered eating and clinical eating disorders. Currently, the interplay between genetic and environmental influences has yet to be elucidated.AimsTo determine whether peer-teasing moderates latent genetic and/or environmental risk for disordered eating among female adolescent twins.MethodFull quantitative gene–environment interplay modelling of longitudinal trajectory of disordered eating in 685 female twins from the Australian Twin Registry.ResultsA model permitting moderation of disordered eating by peer-teasing involving genetic and non-shared environment effects fit these data best. As levels of peer-teasing increased, both genetic and environmental influences on disordered eating strengthened; however, genetic sources increased proportionally more than environmental sources.ConclusionsWeight-related peer-teasing represents a particularly powerful trigger for disordered eating. Nevertheless, it is amenable to intervention/prevention activities spanning individual to universal levels of endeavour.