bluuebunny/crossref_metadata_2025_split huggingface dataset:
Silver nanoparticles defeat p53-positive and p53-negative osteosarcoma cells by triggering mitochondrial stress and apoptosis
Authors: Kovács Dávid , Igaz Nóra , Keskeny Csilla , Bélteky Péter , Tóth Tímea , Gáspár Renáta , Madarász Dániel , Rázga Zsolt , Kónya Zoltán , Boros Imre M. , Kiricsi Mónika 
Published: June 2016

AbstractLoss of function of the tumour suppressor p53 observed frequently in human cancers challenges the drug-induced apoptotic elimination of cancer cells from the body. This phenomenon is a major concern and provides much of the impetus for current attempts to develop a new generation of anticancer drugs capable of provoking apoptosis in a p53-independent manner. Since silver nanoparticles (AgNPs) possess unique cytotoxic features, we examined, whether their activity could be exploited to kill tumour suppressor-deficient cancer cells. Therefore, we investigated the effects of AgNPs on osteosarcoma cells of different p53 genetic backgrounds. As particle diameters might influence the molecular mechanisms leading to AgNP-induced cell death we applied 5 nm and 35 nm sized citrate-coated AgNPs. We found that both sized AgNPs targeted mitochondria and induced apoptosis in wild-type p53-containing U2Os and p53-deficient Saos-2 cells. According to our findings AgNPs are able to kill osteosarcoma cells independently from their actual p53 status and induce p53-independent cancer cell apoptosis. This feature renders AgNPs attractive candidates for novel chemotherapeutic approaches.
Low-Pressure Burst-Mode Focused Ultrasound Wave Reconstruction and Mapping for Blood-Brain Barrier Opening: A Preclinical Examination
Authors: Xia Jingjing , Tsui Po-Hsiang , Liu Hao-Li 
Published: June 2016

AbstractBurst-mode focused ultrasound (FUS) exposure has been shown to induce transient blood-brain barrier (BBB) opening for potential CNS drug delivery. FUS-BBB opening requires imaging guidance during the intervention, yet current imaging technology only enables postoperative outcome confirmation. In this study, we propose an approach to visualize short-burst low-pressure focal beam distribution that allows to be applied in FUS-BBB opening intervention on small animals. A backscattered acoustic-wave reconstruction method based on synchronization among focused ultrasound emission, diagnostic ultrasound receiving and passively beamformed processing were developed. We observed that focal beam could be successfully visualized for in vitro FUS exposure with 0.5–2 MHz without involvement of microbubbles. The detectable level of FUS exposure was 0.467 MPa in pressure and 0.05 ms in burst length. The signal intensity (SI) of the reconstructions was linearly correlated with the FUS exposure level both in-vitro (r2 = 0.9878) and in-vivo (r2 = 0.9943) and SI level of the reconstructed focal beam also correlated with the success and level of BBB-opening. The proposed approach provides a feasible way to perform real-time and closed-loop control of FUS-based brain drug delivery.
Next generation bone tissue engineering: non-viral miR-133a inhibition using collagen-nanohydroxyapatite scaffolds rapidly enhances osteogenesis
Authors: Mencía Castaño Irene , Curtin Caroline M. , Duffy Garry P. , O’Brien Fergal J. 
Published: June 2016

AbstractBone grafts are the second most transplanted materials worldwide at a global cost to healthcare systems valued over $30 billion every year. The influence of microRNAs in the regenerative capacity of stem cells offers vast therapeutic potential towards bone grafting; however their efficient delivery to the target site remains a major challenge. This study describes how the functionalisation of porous collagen-nanohydroxyapatite (nHA) scaffolds with miR-133a inhibiting complexes, delivered using non-viral nHA particles, enhanced human mesenchymal stem cell-mediated osteogenesis through the novel focus on a key activator of osteogenesis, Runx2. This study showed enhanced Runx2 and osteocalcin expression, as well as increased alkaline phosphatase activity and calcium deposition, thus demonstrating a further enhanced therapeutic potential of a biomaterial previously optimised for bone repair applications. The promising features of this platform offer potential for a myriad of applications beyond bone repair and tissue engineering, thus presenting a new paradigm for microRNA-based therapeutics.
Myopic Macular Retinoschisis in Teenagers: Clinical Characteristics and Spectral Domain Optical Coherence Tomography Findings
Authors: Sun Chuan-bin , You Yong-sheng , Liu Zhe , Zheng Lin-yan , Chen Pei-qing , Yao Ke , Xue An-quan 
Published: June 2016

AbstractTo investigate the morphological characteristics of myopic macular retinoschisis (MRS) in teenagers with high myopia, six male (9 eyes) and 3 female (4 eyes) teenagers with typical MRS identified from chart review were evaluated. All cases underwent complete ophthalmic examinations including best corrected visual acuity (BCVA), indirect ophthalmoscopy, colour fundus photography, B-type ultrasonography, axial length measurement and spectral-domain optical coherence tomography (SD-OCT). The average age was 17.8 ± 1.5 years, average refractive error was −17.04 ± 3.04D, average BCVA was 0.43 ± 0.61 and average axial length was 30.42 ± 1.71 mm. Myopic macular degenerative changes (MDC) by colour fundus photographs revealed Ohno-Matsui Category 1 in 4 eyes and Category 2 in 9 eyes. Posterior staphyloma was found in 9 eyes. SD-OCT showed outer MRS in all 13 eyes, internal limiting membrane detachment in 7 eyes, vascular microfolds in 2 eyes and inner MRS in 1 eye. No premacular structures such as macular epiretinal membrane or partially detached posterior hyaloids were found. Our results showed that MRS rarely occurred in highly myopic teenagers and was not accompanied by premacular structures, severe MDC, or even obvious posterior staphyloma. This finding indicates that posterior scleral expansion is probably the main cause of MRS.
Crystallization of Ge2Sb2Te5 thin films by nano- and femtosecond single laser pulse irradiation
Authors: Sun Xinxing , Ehrhardt Martin , Lotnyk Andriy , Lorenz Pierre , Thelander Erik , Gerlach Jürgen W. , Smausz Tomi , Decker Ulrich , Rauschenbach Bernd 
Published: June 2016

AbstractThe amorphous to crystalline phase transformation of Ge2Sb2Te5 (GST) films by UV nanosecond (ns) and femtosecond (fs) single laser pulse irradiation at the same wavelength is compared. Detailed structural information about the phase transformation is collected by x-ray diffraction and high resolution transmission electron microscopy (TEM). The threshold fluences to induce crystallization are determined for both pulse lengths. A large difference between ns and fs pulse irradiation was found regarding the grain size distribution and morphology of the crystallized films. For fs single pulse irradiated GST thin films, columnar grains with a diameter of 20 to 60 nm were obtained as evidenced by cross-sectional TEM analysis. The local atomic arrangement was investigated by high-resolution Cs-corrected scanning TEM. Neither tetrahedral nor off-octahedral positions of Ge-atoms could be observed in the largely defect-free grains. A high optical reflectivity contrast (~25%) between amorphous and completely crystallized GST films was achieved by fs laser irradiation induced at fluences between 13 and 16 mJ/cm2 and by ns laser irradiation induced at fluences between 67 and 130 mJ/cm2. Finally, the fluence dependent increase of the reflectivity is discussed in terms of each photon involved into the crystallization process for ns and fs pulses, respectively.
Design optimisation of AlGaN/GaN metal insulator semiconductor high electron mobility transistor with high‐K/low‐K compound gate dielectric layer for millimeter‐wave application
Authors: Du Jiangfeng , Hou Zehong , Pan Peilin , Bai Zhiyuan , Yu Qi 
Published: June 2016

A novel high DC and radio‐frequency (RF) characteristics AlGaN/GaN metal insulator semiconductor high electron mobility transistor (MIS‐HEMT) with a high‐K/low‐K compound gate dielectric layer (CGD) is proposed. Owing to the different dielectric constants, the discontinuity of the electric field at the high‐K/low‐K interface can modulate the distribution of the electric field along the channel under gate. Hence, enhancement of DC and RF characteristics can be achieved. The optimised results of the AlGaN/GaN MIS‐HEMT with CGD structure revealed that the DC transconductance gm and the maximum saturation current Ids increased about 10.5 and 6.9% compared with the traditional AlGaN/GaN MIS‐HEMT with single high‐K gate dielectric layer (SGD), respectively. Also, the cutoff frequency ft and the maximum oscillation frequency fmax of 74.2 GHz and 129.2 GHz are obtained and improved about 18.5 and 14.7% compared with the device with SGD structure.
Autonomic activity during sleep predicts memory consolidation in humans
Authors: Whitehurst Lauren N. , Cellini Nicola , McDevitt Elizabeth A. , Duggan Katherine A. , Mednick Sara C. 
Published: June 2016

SignificanceWe present the first evidence, to our knowledge, that the autonomic nervous system (ANS) plays a role in associative memory consolidation during sleep. Compared with a Quiet Wake control condition, performance improvement was associated with vagally mediated ANS activity [as measured by high-frequency (HF) heart rate variability (HRV)] during rapid eye movement (REM) sleep. In particular, up to 73% of the proportion of improvement in associative memory performance could be accounted for by considering both traditionally reported sleep features (i.e., minutes spent in sleep stages and sleep spindles) and HF HRV. We hypothesize that central nervous system processes that favor peripheral vagal activity during REM sleep may lead to increases in plasticity that promote associative processing.
Profiling DNA damage-induced phosphorylation in budding yeast reveals diverse signaling networks
Authors: Zhou Chunshui , Elia Andrew E. H. , Naylor Maria L. , Dephoure Noah , Ballif Bryan A. , Goel Gautam , Xu Qikai , Ng Aylwin , Chou Danny M. , Xavier Ramnik J. , Gygi Steven P. , Elledge Stephen J. 
Published: June 2016

Significance
The DNA damage response (DDR) promotes survival and genome maintenance. It involves a network of kinases that phosphorylate a multitude of effector proteins. Although the protein kinases involved have been studied extensively, many targets remain to be discovered. We have used an unbiased approach to profile DDR phosphorylation in budding yeast. We reveal a link between DDR signaling and the metabolic pathways of inositol phosphate and phosphatidyl inositol synthesis, which are required for resistance to DNA damage. Taken together, these data shed new light on the organization of DDR signaling in budding yeast.
Cross-hemispheric dopamine projections have functional significance
Authors: Fox Megan E. , Mikhailova Maria A. , Bass Caroline E. , Takmakov Pavel , Gainetdinov Raul R. , Budygin Evgeny A. , Wightman R. Mark 
Published: June 2016

Significance
Decades of research have described dopamine’s importance in reward-seeking behavior and motor control. Although numerous investigations have focused on dopamine’s mechanisms in modulating behavior, the long-standing belief that dopamine neurons project solely unilaterally has limited the exploration of interhemispheric dopamine signaling. Here we resolve disparate descriptions of unilateral vs. bilateral projections by reporting that dopamine neurons can release dopamine in the contralateral hemisphere. Using voltammetry in awake and anesthetized rats, we reveal an unprecedented synchrony of dopamine fluctuations between hemispheres. Via stimulation with amphetamine, we demonstrate functional cross-hemispheric projections in a hemiparkinsonian model. This previously undescribed capacity for interhemispheric dopamine signaling can precipitate new areas of inquiry. Future work may exploit properties of bilateral dopamine release to improve treatments for Parkinson’s disease, including deep brain stimulation.
A scientific methodology for researching CALL interaction data
Authors: Chanier Thierry , Wigham Ciara R. 
Published: June 2016

This chapter gives an overview of one possible staged methodology for structuring LCI data by presenting a new scientific object, LEarning and TEaching Corpora (LETEC). Firstly, the chapter clarifies the notion of corpora, used in so many different ways in language studies, and underlines how corpora differ from raw language data. Secondly, using examples taken from actual online learning situations, the chapter illustrates the methodology that is used to collect, transform and organize data from online learning situations in order to make them sharable through open-access repositories. The ethics and rights for releasing a corpus as OpenData are discussed. Thirdly, the authors suggest how the transcription of interactions may become more systematic, and what benefits may be expected from analysis tools, before opening the CALL research perspective applied to LCI towards its applications to teacher-training in Computer-Mediated Communication (CMC), and the common interests the CALL field shares with researchers in the field of Corpus Linguistics working on CMC.
Biosynthesis of floral scent 2-phenylethanol in rose flowers
Authors: Hirata Hiroshi , Ohnishi Toshiyuki , Watanabe Naoharu 
Published: June 2016

Abstract
Plants emit chemically diverse volatile compounds for attracting pollinators or putting up a chemical defense against herbivores. 2-Phenylethanol (2PE) is one of the abundantly emitted scent compounds in rose flowers. Feeding experiments with l-[2H8]phenylalanine into rose flowers and subsequent analysis using gas chromatography–mass spectrometry analysis revealed the hypothetical biosynthetic intermediates to [2H8]-2PE, and the biochemical and genetic analyses elucidated the principal pathway to [2H8]-2PE. We recently found season-specific 2PE pathway producing [2H7]-2PE from l-[2H8]phenylalanine. This is a unique example where the dominant pathway to a specific compound changes with the seasons. This review focuses on the biosynthesis of floral volatiles and their regulation to adapt to the changes in the environment.
Unbiased probabilistic taxonomic classification for DNA barcoding
Authors: Somervuo Panu , Koskela Sonja , Pennanen Juho , Henrik Nilsson R. , Ovaskainen Otso 
Published: June 2016

Abstract
Motivation: When targeted to a barcoding region, high-throughput sequencing can be used to identify species or operational taxonomical units from environmental samples, and thus to study the diversity and structure of species communities. Although there are many methods which provide confidence scores for assigning taxonomic affiliations, it is not straightforward to translate these values to unbiased probabilities. We present a probabilistic method for taxonomical classification (PROTAX) of DNA sequences. Given a pre-defined taxonomical tree structure that is partially populated by reference sequences, PROTAX decomposes the probability of one to the set of all possible outcomes. PROTAX accounts for species that are present in the taxonomy but that do not have reference sequences, the possibility of unknown taxonomical units, as well as mislabeled reference sequences. PROTAX is based on a statistical multinomial regression model, and it can utilize any kind of sequence similarity measures or the outputs of other classifiers as predictors.
Results: We demonstrate the performance of PROTAX by using as predictors the output from BLAST, the phylogenetic classification software TIPP, and the RDP classifier. We show that PROTAX improves the predictions of the baseline implementations of TIPP and RDP classifiers, and that it is able to combine complementary information provided by BLAST and TIPP, resulting in accurate and unbiased classifications even with very challenging cases such as 50% mislabeling of reference sequences.
Availability and implementation: Perl/R implementation of PROTAX is available at http://www.helsinki.fi/science/metapop/Software.htm.
Contact: panu.somervuo@helsinki.fi
Supplementary information: Supplementary data are available at Bioinformatics online.
The Effect of the
APOE4
Gene on Accumulation of Aβ
40
After Brain Injury Cannot Be Reversed by Increasing apoE4 Protein
Authors: Washington Patricia M. , Burns Mark P. 
Published: June 2016

Abstract
The apolipoprotein E (apoE) protein is involved in clearance of β-amyloid (Aβ) from the brain; and the APOE4 gene is associated with Aβ plaque formation in humans following traumatic brain injury (TBI). Here, we examined the association between apoE and Aβ 40 after experimental TBI and the effects of APOE alleles on this relationship. We report a biphasic response of soluble apoE protein after TBI with an acute reduction at 1 day postinjury followed by an increase at 7 days postinjury. TBI-induced Aβ 40 levels decreased as soluble apoE levels increased. In APOE4 mice there was a diminished apoE response to TBI that corresponded to prolonged accumulation of TBI-induced Aβ 40 versus that in APOE3 mice. Amyloid precursor protein processing was similar in APOE3 and APOE4 mice suggesting that impaired clearance was responsible for the abnormal accumulation of Aβ 40 in the latter. Treatment of APOE4 mice with bexarotene for 7 days increased apoE4 protein levels but was not sufficient to reduce TBI-induced Aβ 40 . Thus, rapid clearance of TBI-induced Aβ 40 occurs in mice but these pathways are impaired in APOE4 carriers. These data may help explain the deposition of Aβ in APOE4 carriers and the increased incidence of brain Aβ plaques following TBI.
Risk Factors for Herpes Zoster Among Adults
Authors: Marin Mona , Harpaz Rafael , Zhang John , Wollan Peter C. , Bialek Stephanie R. , Yawn Barbara P. 
Published: June 2016

Abstract
Background.  The causes of varicella-zoster virus reactivation and herpes zoster (HZ) are largely unknown. We assessed potential risk factors for HZ, the data for which cannot be obtained from the medical sector.
Methods.  We conducted a matched case-control study. We established active surveillance in Olmsted County, Minnesota to identify HZ occurring among persons age ≥50 years during 2010–2011. Cases were confirmed by medical record review. Herpes zoster-free controls were age- and sex-matched to cases. Risk factor data were obtained by telephone interview.
Results.  We enrolled 389 HZ case patients and 511 matched controls; the median age was 65 and 66 years, respectively. Herpes zoster was associated with family history of HZ (adjusted odds ratio [aOR] = 1.65); association was highest with first-degree or multiple relatives (aOR = 1.87 and 3.08, respectively). Herpes zoster was also associated with prior HZ episodes (aOR = 1.82), sleep disturbance (aOR = 2.52), depression (aOR = 3.81), and recent weight loss (aOR = 1.95). Stress was a risk factor for HZ (aOR = 2.80), whereas a dose-response relationship was not noted. All associations indicated were statistically significant (P &lt; .05). Herpes zoster was not associated with trauma, smoking, tonsillectomy, diet, or reported exposure to pesticides or herbicides (P &gt; .1).
Conclusions.  We identified several important risk factors for HZ; however, the key attributable causes of HZ remain unknown.
Diagnosis and treatment of restless legs syndrome
Authors: Sales Samantha , Sanghera Manjit K. , Klocko David J. , Stewart R. Malcolm 
Published: June 2016

ABSTRACT
Restless legs syndrome (RLS) is a disorder characterized by an irresistible urge to move the legs during rest, usually accompanied by uncomfortable sensations in the affected extremity or extremities. RLS can manifest at any age but prevalence increases with advancing age. This article describes the symptoms of RLS, associated comorbidities, and how to diagnose and manage RLS.
Physician assistant specialty choice
Authors: Morgan Perri , Everett Christine M. , Humeniuk Katherine M. , Valentin Virginia L. 
Published: June 2016

ABSTRACT

Objectives:
To describe trends in physician assistant (PA) specialty distribution, compare these trends with physicians, and quantify the relationship of PA specialty prevalence with both PA and physician salary.

Methods:
PA specialty and salary data were obtained from the 2013 American Academy of PAs' Annual Survey; physician specialty and salary data from the American Medical Association Physician Masterfile and the Medical Group Management Association. Analyses included descriptive statistics and linear regression.

Results:
The proportion of PAs working in primary care decreased from 50% in 1997 to 30% in 2013. Substantial growth in PA proportions occurred in surgical and medical subspecialties. Regression models showed a higher prevalence of PAs in specialties with higher PA salary, higher physician salary, and higher physician-to-PA salary ratio (P<0.05).

Conclusions:
PAs are moving toward subspecialty practice. Our study suggests that demand for PAs may be an important factor driving the trend toward specialization.
Influence of SULT1A1 genetic variation on age at menopause, estrogen levels, and response to hormone therapy in recently postmenopausal white women
Authors: Moyer Ann M. , de Andrade Mariza , Weinshilboum Richard M. , Miller Virginia M. 
Published: June 2016

Abstract

Objective:
Onset and symptoms of menopause, and response to hormone therapy (HT) show large interindividual variability. SULT1A1 encodes for a highly expressed enzyme that metabolizes estrogens. We evaluated the relationship between genetic variation in SULT1A1, menopause age, symptoms, and response to HT.

Methods:
Women enrolled in the Kronos Early Estrogen Prevention Study at Mayo Clinic were randomized to 48 months of treatment with oral conjugated equine estrogen (n = 34), transdermal 17β-estradiol (E2) (n = 33), or placebo (n = 35). Linear regression models and ANOVA were used to test for association of SULT1A1 copy number, rs3760091, rs750155, and rs9282861 (SULT1A1

∗

2), with age at menopause and symptoms, levels of estrogens (estrone [E1], estrone sulfate [E1S], E2, and estradiol sulfate [E2S]), before and after HT.

Results:

SULT1A1 gene copy number affected the minor allele frequency for each single nucleotide polymorphisms tested. Before administration of exogenous hormones, increasing number of G alleles at rs9282861 was associated with earlier age at menopause (P = 0.014), lower frequency of night sweats (P = 0.009), and less severe insomnia (P = 0.046). After 48 months of treatment, SULT1A1 genotype was not associated with the presence of menopausal symptoms. In women randomized to oral conjugated equine estrogen, increasing number of the A allele at rs750155 was associated with lower E1S and E2S (P = 0.004 and 0.017), whereas increasing number of the C allele at rs3760091 was associated with lower E2S/E2 (P = 0.044).

Conclusions:
Interindividual variability in onset of menopause and symptoms before initiation of HT is explained in part by genetic variation in SULT1A1 and may represent a step toward individualizing HT treatment decisions.