bluuebunny/crossref_metadata_2025 huggingface dataset:
Prospective Study of Stereotactic Body Radiation Therapy for Thymoma and Thymic Carcinoma: Therapeutic Effect and Toxicity Assessment
Authors: Hao Xue-jun , Peng Bo , Zhou Zejun , Yang Xue-qin
Published: October 2017

Stereotactic body radiation therapy (SBRT) is an important modality in treatment of tumors. We hypothesized that SBRT can achieve excellent local control with limited toxicity in patients with thymic tumors. A single-institution prospective study was performed with 32 patients who underwent SBRT of thymoma and thymic carcinoma between 2005 and 2014. Thirty-two patients including 39 target lesions were analyses in this study. Almost half of the patients (46.9%) were type C by histopathology and more than half (56.3%) were classified into stage IVA or IVB. The median dose of SBRT for gross tumor volume (GTV) was 56 Gy (range 49–70 Gy). Results showed that the response rate was 96.9% after SBRT and the median tumor shrinkage rate was 62.2% (range 3.8–100%). For the patients with both stage II–III and type A-B (n = 6), the median PFS was 28 months. In-field failure was only observed in 4 patients, and outside-field failure was seen in 2 patients. The local control rate was 81.25%. Patients treated with SBRT had an excellent local control with mild toxicities, which suggests that SBRT is feasible for the patients with thymic tumors who are unable to undergo either surgery or conventionally fractionated radiation therapy.
Branched-chain amino acids and Alzheimer’s disease: a Mendelian randomization analysis
Authors: Larsson Susanna C. , Markus Hugh S.
Published: October 2017

We conducted a two-sample Mendelian randomization study to test the hypothesis that raised plasma levels of the branched-chain amino acids isoleucine, leucine, and valine are associated with Alzheimer’s disease (AD). From a genome-wide association study of 16,596 individuals of European ancestry, we obtained summary statistics for four independent single nucleotide polymorphisms (SNPs) associated with isoleucine levels and one SNP associated with both leucine and valine levels at genome-wide significance. Summary statistics of the associations of the five SNPs with AD were obtained from the International Genomics of Alzheimer’s Project (17,008 AD cases and 37,154 controls). Based on four SNPs, the odds ratio of AD per genetically predicted one standard deviation higher isoleucine levels was 1.35 (95% CI, 1.08–1.69; p = 0.007). The leucine- and valine-raising allele was not associated with AD (p = 0.46). These data suggest that a genetic predisposition to raised plasma isoleucine levels is positively associated with AD.
Auditory evoked BOLD responses in awake compared to lightly anaesthetized zebra finches
Authors: Van Ruijssevelt L. , Hamaide J. , Van Gurp M. T. , Verhoye M. , Van der Linden A.
Published: October 2017

Functional magnetic resonance imaging (fMRI) is increasingly used in cognitive neuroscience and has become a valuable tool in the study of auditory processing in zebra finches, a well-established model of learned vocal communication. Due to its sensitivity to head motion, most fMRI studies in animals are performed in anaesthetized conditions, which might significantly impact neural activity evoked by stimuli and cognitive tasks. In this study, we (1) demonstrate the feasibility of fMRI in awake zebra finches and (2) explore how light anaesthesia regimes affect auditory-evoked BOLD responses to biologically relevant songs. After an acclimation procedure, we show that fMRI can be successfully performed during wakefulness, enabling the detection of reproducible BOLD responses to sound. Additionally, two light anaesthesia protocols were tested (isoflurane and a combination of medetomidine and isoflurane), of which isoflurane alone appeared to be the most promising given the high success rate, non-invasive induction, and quick recovery. By comparing auditory evoked BOLD responses in awake versus lightly anaesthetized conditions, we observed overall effects of anaesthetics on cerebrovascular reactivity as reflected in the extent of positive and negative BOLD responses. Further, our results indicate that light anaesthesia has limited effects on selective BOLD responses to natural versus synthetic sounds.
An integrated EEG and eye-tracking approach for the study of responding and initiating joint attention in Autism Spectrum Disorders
Authors: Billeci Lucia , Narzisi Antonio , Tonacci Alessandro , Sbriscia-Fioretti Beatrice , Serasini Luca , Fulceri Francesca , Apicella Fabio , Sicca Federico , Calderoni Sara , Muratori Filippo
Published: October 2017

Autism Spectrum Disorders (ASD) are characterised by impairment in joint attention (JA), which has two components: the response to JA and the initiation of JA. Literature suggests a correlation between JA and neural circuitries, although this link is still largely unexplored in ASD. In this pilot study, we aimed at investigating the neural correlates of responding and initiating JA in high-functioning children with ASD and evaluating the changes in brain function and visual pattern after six months of rehabilitative treatment using an integrated EEG/eye-tracking system. Our results showed that initiating and responding JA subtend both overlapping (i.e. frontal and temporal) and specialized (i.e. parietal for responding JA and occipital for initiating JA) neural circuitries. In addition, in a subgroup of subjects, we observed trends of changes in both brain activity and connectivity after rehabilitative treatment in both the two tasks, which were correlated with modifications in gaze measures. These preliminary results, if confirmed in a larger sample, suggest the feasibility of using the proposed multimodal approach to characterise JA-related brain circuitries and visual pattern in ASD individuals and to monitor longitudinal changes in response to rehabilitative intervention.
Nucleation and annihilation of skyrmions in Mn2CoAl observed through the topological Hall effect
Authors: Ludbrook B. M. , Dubuis G. , Puichaud A.-H. , Ruck B. J. , Granville S.
Published: October 2017

Magnetic skyrmions are topologically protected spin textures with great technological potential. These topologically non-trivial non-coplanar spin textures give rise to a topological Hall effect, enabling the purely electronic detection of magnetic skyrmions. We report a clear topological Hall effect in thin films of the the Heusler alloy Mn2CoAl, a ferromagnetic spin-gapless semiconductor, capped by a thin layer of Pd. We exploit the strong thickness- and temperature-dependence of the anomalous Hall effect in this system, tuning it to zero to enable the unambiguous measurement of the topological Hall effect, which is observed for temperatures between 3 K and 280 K. The topological Hall effect is evidence of skyrmions, and we demonstrate the simultaneous coexistence of opposite polarity skyrmions using a novel method involving minor field loops of the Hall effect.
Large-scale genomic analyses reveal the population structure and evolutionary trends of Streptococcus agalactiae strains in Brazilian fish farms
Authors: Barony Gustavo M. , Tavares Guilherme C. , Pereira Felipe L. , Carvalho Alex F. , Dorella Fernanda A. , Leal Carlos A. G. , Figueiredo Henrique C. P.
Published: October 2017

Streptococcus agalactiae is a major pathogen and a hindrance on tilapia farming worldwide. The aims of this work were to analyze the genomic evolution of Brazilian strains of S. agalactiae and to establish spatial and temporal relations between strains isolated from different outbreaks of streptococcosis. A total of 39 strains were obtained from outbreaks and their whole genomes were sequenced and annotated for comparative analysis of multilocus sequence typing, genomic similarity and whole genome multilocus sequence typing (wgMLST). The Brazilian strains presented two sequence types, including a newly described ST, and a non-typeable lineage. The use of wgMLST could differentiate each strain in a single clone and was used to establish temporal and geographical correlations among strains. Bayesian phylogenomic analysis suggests that the studied Brazilian population was co-introduced in the country with their host, approximately 60 years ago. Brazilian strains of S. agalactiae were shown to be heterogeneous in their genome sequences and were distributed in different regions of the country according to their genotype, which allowed the use of wgMLST analysis to track each outbreak event individually.
Evaluating feasibility of an automated 3-dimensional scanner using Raman spectroscopy for intraoperative breast margin assessment
Authors: Thomas G. , Nguyen T.-Q. , Pence I. J. , Caldwell B. , O’Connor M. E. , Giltnane J. , Sanders M. E. , Grau A. , Meszoely I. , Hooks M. , Kelley M. C. , Mahadevan-Jansen A.
Published: October 2017

Breast conserving surgery is the preferred treatment for women diagnosed with early stage invasive breast cancer. To ensure successful breast conserving surgeries, efficient tumour margin resection is required for minimizing tumour recurrence. Currently surgeons rely on touch preparation cytology or frozen section analysis to assess tumour margin status intraoperatively. These techniques have suboptimal accuracy and are time-consuming. Tumour margin status is eventually confirmed using postoperative histopathology that takes several days. Thus, there is a need for a real-time, accurate, automated guidance tool that can be used during tumour resection intraoperatively to assure complete tumour removal in a single procedure. In this paper, we evaluate feasibility of a 3-dimensional scanner that relies on Raman Spectroscopy to assess the entire margins of a resected specimen within clinically feasible time. We initially tested this device on a phantom sample that simulated positive tumour margins. This device first scans the margins of the sample and then depicts the margin status in relation to an automatically reconstructed image of the phantom sample. The device was further investigated on breast tissues excised from prophylactic mastectomy specimens. Our findings demonstrate immense potential of this device for automated breast tumour margin assessment to minimise repeat invasive surgeries.
Ophthalmological symptoms in children with intracranial cysts
Authors: Gotz Wieckowska Anna , Glowka Lidia , Brazert Agata , Pawlak Marta
Published: October 2017

The purpose of this study was to perform an ophthalmological assessment in children with intracranial cysts and to assess the correlation between the occurrence of cysts and visual disorders. The documentation of 46 children with intracranial cysts, monitored by the Children’s Outpatient Ophthalmology Clinic, Poznan, Poland was analysed. The best corrected visual acuity (BCVA), the alignment of the eyes, visual evoked potentials (VEP), comprehensive eye examination were performed in all patients. Additional ophthalmological tests were conducted to eliminate other causes of decreased visual acuity.Included in the final analysis were 26 children (52 eyes). The average age at the last visit was 10.3 years. Sixteen children (61.5%) had arachnoid cysts located in the posterior cranial fossa, 3 children (11.5%) in the middle cranial fossa, while 7 children (27%) had a pineal cyst. Decreased BCVA was found in 13 children, abnormal VEP in 13, strabismus in 14 patients (53.9%), nystagmus in 5 patients (19.2%), and double vision in 2 patients (7.7%). Numerous visual disorders in children with intracranial cysts suggest the necessity to carry out enhanced ophthalmological diagnostics in these patients. In the examined patient group, visual disorders occurred mostly in the case of arachnoid cysts of the posterior fossa.
CCAAT/Enhancer binding protein β silencing mitigates glial activation and neurodegeneration in a rat model of Parkinson’s disease
Authors: Morales-Garcia Jose A. , Gine Elena , Hernandez-Encinas Elena , Aguilar-Morante Diana , Sierra-Magro Ana , Sanz-SanCristobal Marina , Alonso-Gil Sandra , Sanchez-Lanzas Raul , Castaño Jose G. , Santos Angel , Perez-Castillo Ana
Published: October 2017

The CCAAT/Enhancer binding protein β (C/EBPβ) is a transcription factor involved in numerous physiological as well as pathological conditions in the brain. However, little is known regarding its possible role in neurodegenerative disorders. We have previously shown that C/EBPβ regulates the expression of genes involved in inflammatory processes and brain injury. Here, we have analyzed the effects of C/EBPβ interference in dopaminergic cell death and glial activation in the 6-hydroxydopamine model of Parkinson’s disease. Our results showed that lentivirus-mediated C/EBPβ deprivation conferred marked in vitro and in vivo neuroprotection of dopaminergic cells concomitant with a significant attenuation of the level of the inflammatory response and glial activation. Additionally, C/EBPβ interference diminished the induction of α-synuclein in the substantia nigra pars compacta of animals injected with 6-hydroxydopamine. Taking together, these results reveal an essential function for C/EBPβ in the pathways leading to inflammatory-mediated brain damage and suggest novel roles for C/EBPβ in neurodegenerative diseases, specifically in Parkinson’s disease, opening the door for new therapeutic interventions.
Longitudinal assessment of HLA and MIC-A antibodies in uneventful pregnancies and pregnancies complicated by preeclampsia or gestational diabetes
Authors: Küssel Lorenz , Herkner Harald , Wahrmann Markus , Eskandary Farsad , Doberer Konstantin , Binder Julia , Pateisky Petra , Zeisler Harald , Böhmig Georg A. , Bond Gregor
Published: October 2017

The significance of antibodies directed against paternal epitopes in the context of obstetric disorders is discussed controversially. In this study anti-HLA and anti-MIC-A antibodies were analysed in sera of women with uneventful pregnancy (n = 101), preeclampsia (PE, n = 55) and gestational diabetes (GDM, n = 36) using antigen specific microbeads. While two thirds of the women with uneventful pregnancy or GDM were HLA and MIC-A antibody positive in gestational week 11 to 13 with a modest increase towards the end of pregnancy, women with PE showed an inverse kinetic: 90% were HLA antibody positive in gestational week 11 to 13 and only 10% showed HLA reactivities at the end of the pregnancy. HLA antibody binding strength was more pronounced in gestational week 14 to 17 in patients with PE compared to women with uneventful pregnancy (maximum median fluorescence intensity of the highest ranked positive bead 7403, IQR 2193–7938 vs. 1093, IQR 395–5689; p = 0.04) and was able to predict PE with an AUC of 0.80 (95% CI 0.67–0.93; p = 0.002). Our data suggest a pathophysiological involvement of HLA antibodies in PE. HLA antibody quantification in early pregnancy may provide a useful tool to increase diagnostic awareness in women prone to develop PE.
Feasibility and physiological relevance of designing highly potent aminopeptidase-sparing leukotriene A4 hydrolase inhibitors
Authors: Numao Shin , Hasler Franziska , Laguerre Claire , Srinivas Honnappa , Wack Nathalie , Jäger Petra , Schmid Andres , Osmont Arnaud , Röthlisberger Patrik , Houguenade Jeremy , Bergsdorf Christian , Dawson Janet , Carte Nathalie , Hofmann Andreas , Markert Christian , Hardaker Liz , Billich Andreas , Wolf Romain M. , Penno Carlos A. , Bollbuck Birgit , Miltz Wolfgang , Röhn Till A.
Published: October 2017

Leukotriene A4 Hydrolase (LTA4H) is a bifunctional zinc metalloenzyme that comprises both epoxide hydrolase and aminopeptidase activity, exerted by two overlapping catalytic sites. The epoxide hydrolase function of the enzyme catalyzes the biosynthesis of the pro-inflammatory lipid mediator leukotriene (LT) B4. Recent literature suggests that the aminopeptidase function of LTA4H is responsible for degradation of the tripeptide Pro-Gly-Pro (PGP) for which neutrophil chemotactic activity has been postulated. It has been speculated that the design of epoxide hydrolase selective LTA4H inhibitors that spare the aminopeptidase pocket may therefore lead to more efficacious anti-inflammatory drugs. In this study, we conducted a high throughput screen (HTS) for LTA4H inhibitors and attempted to rationally design compounds that would spare the PGP degrading function. While we were able to identify compounds with preference for the epoxide hydrolase function, absolute selectivity was not achievable for highly potent compounds. In order to assess the relevance of designing such aminopeptidase-sparing LTA4H inhibitors, we studied the role of PGP in inducing inflammation in different settings in wild type and LTA4H deficient (LTA4H KO) animals but could not confirm its chemotactic potential.  Attempting to design highly potent epoxide hydrolase selective LTA4H inhibitors, therefore seems to be neither feasible nor relevant.
Virulence Characteristics of Carbapenem-Resistant Klebsiella pneumoniae Strains from Patients with Necrotizing Skin and Soft Tissue Infections
Authors: Krapp Fiorella , Morris Andrew R. , Ozer Egon A. , Hauser Alan R.
Published: October 2017

Two types of Klebsiella pneumoniae (KP) strains are currently emerging: hypervirulent (hvKP) strains and carbapenem-resistant (CR-KP) strains. To date, these two strain types rarely overlap. Recent reports, however, suggest that CR-KP strains are increasing in virulence. hvKP strains frequently present as highly invasive infections, such as necrotizing skin and soft tissue infections (NSSTI). To examine whether CR-KP strains with features of hvKP were present in our U.S. hospital, we retrospectively identified four cases of CR-KP NSSTI diagnosed between January 2012 and January 2016. Whole-genome sequencing was used to perform multilocus sequence typing, capsular typing, and identification of virulence and antimicrobial resistance genes. Additionally, the virulence of each isolate was determined in vitro and using murine pneumonia and subcutaneous infection models. We identified one CR-KP isolate that possessed features of hypervirulent KP, including a hypermucoviscous phenotype, K2 capsule, and resistance to phagocytosis. Of the four CR-KP isolates, two had no evidence of enhanced pathogenicity in either mouse model, demonstrating that low-virulence strains can cause NSSTI in immunosuppressed patients. The remaining two isolates exhibited low virulence in the pneumonia model but high virulence in the subcutaneous infection model, suggesting that the virulence attributes of these isolates are adapted to causing NSSTI.
Microarray gene expression of periosteum in spontaneous bone regeneration of mandibular segmental defects
Authors: Li Zheyi , Pan Juli , Ma Jinling , Zhang Zhen , Bai Yuxing
Published: October 2017

Spontaneous bone regeneration could occur to reestablish mandibular bony continuity in patients who underwent partial or total mandibulectomy for tumors with periosteum-preserving. However, scarce data is available related to the precise role of periosteum in this bone regeneration. Therefore we aimed to investigate the gene expression of periosteum that were involved in the mandibular bone regeneration. Mandibular segmental defects were created in six mini-pigs with periosteum preserved. The periosteum of defects and control site were harvested at 1 and 2 weeks. Gene ontology (GO) analysis showed that the mechanisms concerning immature wound healing were clearly up-regulated at week 1. In contrast, by week-2, the GO categories of skeletal development, ossification and bone mineralization were significantly over-represented at week-2 with several genes encoding cell differentiation, extracellular matrix formation, and anatomical structure development. Furthermore, Tgfβ/Bmp, Wnt and Notch signaling were all related to the osteogenic process in this study. Besides osteogenesis, genes related to angiogenesis and neurogenesis were also prominent at week-2. These findings revealed that the gene expression profile of the periosteum’s cells participating in bone regeneration varied in different time points, and numbers of candidate genes that differentially expressed during early healing stages of intramembranous bone regeneration were suggested.
Gut microbiome alterations in Alzheimer’s disease
Authors: Vogt Nicholas M. , Kerby Robert L. , Dill-McFarland Kimberly A. , Harding Sandra J. , Merluzzi Andrew P. , Johnson Sterling C. , Carlsson Cynthia M. , Asthana Sanjay , Zetterberg Henrik , Blennow Kaj , Bendlin Barbara B. , Rey Federico E.
Published: October 2017

Alzheimer’s disease (AD) is the most common form of dementia. However, the etiopathogenesis of this devastating disease is not fully understood. Recent studies in rodents suggest that alterations in the gut microbiome may contribute to amyloid deposition, yet the microbial communities associated with AD have not been characterized in humans. Towards this end, we characterized the bacterial taxonomic composition of fecal samples from participants with and without a diagnosis of dementia due to AD. Our analyses revealed that the gut microbiome of AD participants has decreased microbial diversity and is compositionally distinct from control age- and sex-matched individuals. We identified phylum- through genus-wide differences in bacterial abundance including decreased Firmicutes, increased Bacteroidetes, and decreased Bifidobacterium in the microbiome of AD participants. Furthermore, we observed correlations between levels of differentially abundant genera and cerebrospinal fluid (CSF) biomarkers of AD. These findings add AD to the growing list of diseases associated with gut microbial alterations, as well as suggest that gut bacterial communities may be a target for therapeutic intervention.
Prothrombin G20210A (rs1799963) polymorphism increases myocardial infarction risk in an age-related manner: A systematic review and meta-analysis
Authors: Li Changlong , Ren Hui , Chen Hong , Song Junxian , Li Sufang , Lee Chongyou , Liu Jun , Cui Yuxia
Published: October 2017

G20210A polymorphism (rs1799963) within the prothrombin gene is associated with a higher circulation level of prothrombin, thus increasing the likelihood of developing myocardial infarction (MI). Opinions differ regarding the correlation between prothrombin G20210A genotype and MI risk, which prompted us to conduct a meta-analysis to determine this association. PubMed, EMBASE, Web of Science and CNKI were searched for pertinent reports. A total of 34 studies involving 14 611 MI cases and 84 358 controls were analyzed in this quantitative analysis. We found a statistically significant association between prothrombin G20210A polymorphism and MI in the allele model (A vs. G, OR = 1.43, 95%CI: 1.18–1.72), heterozygote model (GA vs. GG, OR = 1.41, 95%CI: 1.16–1.72) and dominant model (GA + AA vs. GG, OR = 1.41, 95%CI: 1.15–1.72). The association remains significant in Caucasians but not in non-Caucasians. Moreover, prothrombin G20210A polymorphism increases MI risk in an age-related manner. A further significant association was found in a subpopulation younger than 55 years (allele model, OR = 1.76, 95%CI: 1.32–2.35; heterozygote model, OR = 1.70, 95%CI: 1.24–2.33; dominant model, OR = 1.70, 95%CI: 1.24–2.34). Sensitivity analysis and publication bias analysis revealed stable and statistically robust results. Our meta-analysis demonstrated that prothrombin G20210A polymorphism may represent a risk factor for MI.
Estimating prognosis in patients with acute myocardial infarction using personalized computational heart models
Authors: Gao Hao , Mangion Kenneth , Carrick David , Husmeier Dirk , Luo Xiaoyu , Berry Colin
Published: October 2017

Biomechanical computational models have potential prognostic utility in patients after an acute ST-segment–elevation myocardial infarction (STEMI). In a proof-of-concept study, we defined two groups (1) an acute STEMI group (n = 6, 83% male, age 54 ± 12 years) complicated by left ventricular (LV) systolic dysfunction; (2) an age- and sex- matched hyper-control group (n = 6, 83% male, age 46 ± 14 years), no prior history of cardiovascular disease and normal systolic blood pressure (SBP < 130 mmHg). Cardiac MRI was performed in the patients (2 days & 6 months post-STEMI) and the volunteers, and biomechanical heart models were synthesized for each subject. The candidate parameters included normalized active tension (ATnorm) and active tension at the resting sarcomere length (Treq, reflecting required contractility). Myocardial contractility was inversely determined from personalized heart models by matching CMR-imaged LV dynamics. Compared with controls, patients with recent STEMI exhibited increased LV wall active tension when normalized by SBP. We observed a linear relationship between Treq 2 days post-MI and global longitudinal strain 6 months later (r = 0.86; p = 0.03). Treq may be associated with changes in LV function in the longer term in STEMI patients complicated by LV dysfunction. Further studies seem warranted.
Micro-ribonucleic acids and extracellular vesicles repertoire in the spent culture media is altered in women undergoing In Vitro Fertilization
Authors: Abu-Halima Masood , Häusler Sebastian , Backes Christina , Fehlmann Tobias , Staib Claudia , Nestel Sigrun , Nazarenko Irina , Meese Eckart , Keller Andreas
Published: October 2017

MicroRNAs (miRNAs) are class of small RNA molecules with major impact on gene regulation. We analyzed the potential of miRNAs secreted from pre-implantation embryos into the embryonic culture media as biomarkers to predict successful pregnancy. Using microarray analysis, we profiled the miRNome of the 56 spent culture media (SCM) after embryos transfer and found a total of 621 miRNAs in the SCM. On average, we detected 163 miRNAs in SCM of samples with failed pregnancies, but only 149 SCM miRNAs of embryos leading to pregnancies. MiR-634 predicted an embryo transfer leading to a positive pregnancy with an accuracy of 71% and a sensitivity of 85%. Among the 621 miRNAs, 102 (16.4%) showed a differential expression between positive and negative outcome of pregnancy with miR-29c-3p as the most significantly differentially expressed miRNA. The number of extracellular vehicles was lower in SCM with positive outcomes (3.8 × 109/mL EVs), as compared to a negative outcome (7.35 × 109/mL EVs) possibly explaining the reduced number of miRNAs in the SCM associated with failed pregnancies. The analysis of the miRNome in the SCM of couples undergoing fertility treatment lays the ground towards development of biomarkers to predict successful pregnancy and towards understanding the role of embryonic miRNAs found in the SCM.
Rainbow-trapping absorbers: Broadband, perfect and asymmetric sound absorption by subwavelength panels for transmission problems
Authors: Jiménez Noé , Romero-García Vicent , Pagneux Vincent , Groby Jean-Philippe
Published: October 2017

Perfect, broadband and asymmetric sound absorption is theoretically, numerically and experimentally reported by using subwavelength thickness panels in a transmission problem. The panels are composed of a periodic array of varying crosssection waveguides, each of them being loaded by Helmholtz resonators (HRs) with graded dimensions. The low cut-off frequency of the absorption band is fixed by the resonance frequency of the deepest HR, that reduces drastically the transmission. The preceding HR is designed with a slightly higher resonance frequency with a geometry that allows the impedance matching to the surrounding medium. Therefore, reflection vanishes and the structure is critically coupled. This results in perfect sound absorption at a single frequency. We report perfect absorption at 300 Hz for a structure whose thickness is 40 times smaller than the wavelength. Moreover, this process is repeated by adding HRs to the waveguide, each of them with a higher resonance frequency than the preceding one. Using this frequency cascade effect, we report quasi-perfect sound absorption over almost two frequency octaves ranging from 300 to 1000 Hz for a panel composed of 9 resonators with a total thickness of 11 cm, i.e., 10 times smaller than the wavelength at 300 Hz.
2D Raman band splitting in graphene: Charge screening and lifting of the K-point Kohn anomaly
Authors: Wang Xuanye , Christopher Jason W. , Swan Anna K.
Published: October 2017

Pristine graphene encapsulated in hexagonal boron nitride has transport properties rivalling suspended graphene, while being protected from contamination and mechanical damage. For high quality devices, it is important to avoid and monitor accidental doping and charge fluctuations. The 2D Raman double peak in intrinsic graphene can be used to optically determine charge density, with decreasing peak split corresponding to increasing charge density. We find strong correlations between the 2D1 and 2D2 split vs 2D line widths, intensities, and peak positions. Charge density fluctuations can be measured with orders of magnitude higher precision than previously accomplished using the G-band shift with charge. The two 2D intrinsic peaks can be associated with the “inner” and “outer” Raman scattering processes, with the counterintuitive assignment of the phonon closer to the K point in the KM direction (outer process) as the higher energy peak. Even low charge screening lifts the phonon Kohn anomaly near the K point for graphene encapsulated in hBN, and shifts the dominant intensity from the lower to the higher energy peak.
Prediction of recurrence in early stage non-small cell lung cancer using computer extracted nuclear features from digital H&E images
Authors: Wang Xiangxue , Janowczyk Andrew , Zhou Yu , Thawani Rajat , Fu Pingfu , Schalper Kurt , Velcheti Vamsidhar , Madabhushi Anant
Published: October 2017

Identification of patients with early stage non-small cell lung cancer (NSCLC) with high risk of recurrence could help identify patients who would receive additional benefit from adjuvant therapy. In this work, we present a computational histomorphometric image classifier using nuclear orientation, texture, shape, and tumor architecture to predict disease recurrence in early stage NSCLC from digitized H&E tissue microarray (TMA) slides. Using a retrospective cohort of early stage NSCLC patients (Cohort #1, n = 70), we constructed a supervised classification model involving the most predictive features associated with disease recurrence. This model was then validated on two independent sets of early stage NSCLC patients, Cohort #2 (n = 119) and Cohort #3 (n = 116). The model yielded an accuracy of 81% for prediction of recurrence in the training Cohort #1, 82% and 75% in the validation Cohorts #2 and #3 respectively. A multivariable Cox proportional hazard model of Cohort #2, incorporating gender and traditional prognostic variables such as nodal status and stage indicated that the computer extracted histomorphometric score was an independent prognostic factor (hazard ratio = 20.81, 95% CI: 6.42–67.52, P < 0.001).
Studying the role of axon fasciculation during development in a computational model of the Xenopus tadpole spinal cord
Authors: Davis Oliver , Merrison-Hort Robert , Soffe Stephen R. , Borisyuk Roman
Published: October 2017

During nervous system development growing axons can interact with each other, for example by adhering together in order to produce bundles (fasciculation). How does such axon-axon interaction affect the resulting axonal trajectories, and what are the possible benefits of this process in terms of network function? In this paper we study these questions by adapting an existing computational model of the development of neurons in the Xenopus tadpole spinal cord to include interactions between axons. We demonstrate that even relatively weak attraction causes bundles to appear, while if axons weakly repulse each other their trajectories diverge such that they fill the available space. We show how fasciculation can help to ensure axons grow in the correct location for proper network formation when normal growth barriers contain gaps, and use a functional spiking model to show that fasciculation allows the network to generate reliable swimming behaviour even when overall synapse counts are artificially lowered. Although we study fasciculation in one particular organism, our approach to modelling axon growth is general and can be widely applied to study other nervous systems.
Pinned domain wall oscillator as a tuneable direct current spin wave emitter
Authors: Voto Michele , Lopez-Diaz Luis , Martinez Eduardo
Published: October 2017

Local perturbations in the relative orientation of the magnetic moments in a continuous magnetic system can propagate in the form of waves. These so-called spin waves represent a promising candidate as an information carrier for spin-based low-power applications. A localized, energy-efficient excitation of coherent and short-wavelength spin waves is a crucial technological requirement, and alternatives to excitation via the Oersted field of an alternating current must be explored. Here, we show how a domain wall pinned at a geometrical constriction in a perpendicularly magnetized thin nanowire emits spin waves when forced to rotate by the application of a low direct current flowing along the wire. Spin waves are excited by the in-plane stray field of the rotating domain wall and propagate at an odd harmonic of the domain wall rotation frequency in the direction of the electron’s flow. The application of an external field, opposing domain wall depinning induced by the current, breaks the symmetry for spin wave propagation in the two domains, allowing emission in both directions but at different frequencies. The results presented define a new approach to manufacture tuneable high-frequency spin wave emitters of easy fabrication and low power consumption.
Direct estimation of de novo mutation rates in a chimpanzee parent-offspring trio by ultra-deep whole genome sequencing
Authors: Tatsumoto Shoji , Go Yasuhiro , Fukuta Kentaro , Noguchi Hideki , Hayakawa Takashi , Tomonaga Masaki , Hirai Hirohisa , Matsuzawa Tetsuro , Agata Kiyokazu , Fujiyama Asao
Published: October 2017

Mutations generate genetic variation and are a major driving force of evolution. Therefore, examining mutation rates and modes are essential for understanding the genetic basis of the physiology and evolution of organisms. Here, we aim to identify germlinede novomutations through the whole-genome surveyance of Mendelian inheritance error sites (MIEs), those not inherited through the Mendelian inheritance manner from either of the parents, using ultra-deep whole genome sequences (>150-fold) from a chimpanzee parent-offspring trio. We identified such 889 MIEs and classified them into four categories based on the pattern of inheritance and the sequence read depth: [i]de novosingle nucleotide variants (SNVs), [ii] copy number neutral inherited variants, [iii] hemizygous deletion inherited variants, and [iv]de novocopy number variants (CNVs). Fromde novoSNV candidates, we estimated a germlinede novoSNV mutation rate as 1.48 × 10−8per site per generation or 0.62 × 10−9per site per year. In summary, this study demonstrates the significance of ultra-deep whole genome sequencing not only for the direct estimation of mutation rates but also for discerning various mutation modes includingde novoallelic conversion andde novoCNVs by identifying MIEs through the transmission of genomes from parents to offspring.
Marine self-potential survey for exploring seafloor hydrothermal ore deposits
Authors: Kawada Yoshifumi , Kasaya Takafumi
Published: October 2017

We conducted a self-potential survey at an active hydrothermal field, the Izena hole in the mid-Okinawa Trough, southern Japan. This field is known to contain Kuroko-type massive sulphide deposits. This survey measured the self-potential continuously in ambient seawater using a deep-tow array, which comprises an electrode array with a 30-m-long elastic rod and a stand-alone data acquisition unit. We observed negative self-potential signals not only above active hydrothermal vents and visible sulphide mounds but also above the flat seafloor without such structures. Some signals were detectable >50 m above the seafloor. Analysis of the acquired data revealed these signals’ source as below the seafloor, which suggests that the self-potential method can detect hydrothermal ore deposits effectively. The self-potential survey, an easily performed method for initial surveys, can identify individual sulphide deposits from a vast hydrothermal area.
Mesenchymal stem/stromal cells enhance engraftment, vasculogenic and pro-angiogenic activities of endothelial colony forming cells in immunocompetent hosts
Authors: Shafiee Abbas , Patel Jatin , Lee James S. , Hutmacher Dietmar W. , Fisk Nicholas M. , Khosrotehrani Kiarash
Published: October 2017

The clinical use of endothelial colony forming cells (ECFC) is hampered by their restricted engraftment. We aimed to assess engraftment, vasculogenic and pro-angiogenic activities of ECFC in immunocompetent (C57BL/6: WT) or immunodeficient (rag1−/−C57BL/6: Rag1) mice. In addition, the impact of host immune system was investigated where ECFC were co-implanted with mesenchymal stem/stromal cells (MSC) from adult bone marrow (AdBM-MSC), fetal bone marrow (fBM-MSC), fetal placental (fPL-MSC), or maternal placental (MPL-MSC). Transplantation of ECFCs in Matrigel plugs resulted in less cell engraftment in WT mice compared to Rag1 mice. Co-implantation with different MSCs resulted in a significant increase in cell engraftment up to 9 fold in WT mice reaching levels of engraftment observed when using ECFCs alone in Rag1 mice but well below levels of engraftment with MSC-ECFC combination in Rag1 recipients. Furthermore, MSCs did not reduce murine splenic T cell proliferation in response to ECFCsin vitro. ECFCs enhanced the murine neo-vascularization through paracrine effect, but with no difference between Rag1 and WT mice. In conclusions, the host adaptive immune system affects the engraftment of ECFCs. MSC co-implantation improves ECFC engraftment and function even in immunocompetent hosts mostly through non-immune mechanisms.
Substrate recognition by two different P450s: Evidence for conserved roles in a common fold
Authors: Tietz Drew R. , Colthart Allison M. , Sondej Pochapsky Susan , Pochapsky Thomas C.
Published: October 2017

Cytochrome P450 monooxygenases CYP101A1 and MycG catalyze regio- and stereospecific oxidations of their respective substrates, d-camphor and mycinamicin IV. Despite the low sequence homology between the two enzymes (29% identity) and differences in size and hydrophobicity of their substrates, the conformational changes that occur upon substrate binding in both enzymes as determined by solution NMR methods show some striking similarities. Many of the same secondary structural features in both enzymes are perturbed, suggesting the existence of a common mechanism for substrate binding and recognition in the P450 superfamily.
Liquid-infused nitric oxide-releasing (LINORel) silicone for decreased fouling, thrombosis, and infection of medical devices
Authors: Goudie Marcus J. , Pant Jitendra , Handa Hitesh
Published: October 2017

Recent reports on liquid-infused materials have shown promise in creating ultra-low fouling surfaces, but are limited in their ability to prevent bacterial proliferation and prevent platelet activation in blood-contacting applications. In this work, a liquid-infused nitric oxide-releasing (LINORel) material is created by incorporating the nitric oxide (NO) donorS-nitroso-acetylpenicillamine (SNAP) and silicone oil in commercial medical grade silicone rubber tubing through a solvent swelling process. This combination provides several key advantages over previous NO-releasing materials, including decreased leaching of NO donor, controlled release of NO, and maintenance of ultra-low fouling property of liquid-infused materials. The LINORel tubing reduces protein adhesion as observed using fluorescence imaging, and platelet adhesion (81.7 ± 2.5%)in vitroover a 2 h period. The LINORel combination greatly reduces bacterial adhesion and biofilm formation of two most common pathogens responsible for hospital acquired infections: gram-positiveStaphylococcus aureusand gram-negativePseudomonas aeruginosa(99.3 ± 1.9% and 88.5 ± 3.3% respectively) over a 7-day period in a CDC bioreactor environment. Overall, the LINORel approach provides a synergistic combination of active and passive non-fouling approaches to increase biocompatibility and reduce infection associated with medical devices.
Porous nitrogen-enriched carbonaceous material from marine waste: chitosan-derived carbon nitride catalyst for aerial oxidation of 5-hydroxymethylfurfural (HMF) to 2,5-furandicarboxylic acid
Authors: Verma Sanny , Nadagouda Mallikarjuna N. , Varma Rajender S.
Published: October 2017

Chitosan-derived, porous nitrogen-enriched carbonaceous carbon nitride catalyst (PCNx) has been synthesized from marine waste and its use demonstrated in a metal-free heterogeneous selective oxidation of 5-hydroxymethyl-furfural (HMF) to 2,5-furandicarboxylic acid (FDCA) using aerial oxygen under mild reaction conditions.
Person identification from aerial footage by a remote-controlled drone
Authors: Bindemann Markus , Fysh Matthew C. , Sage Sophie S. K. , Douglas Kristina , Tummon Hannah M.
Published: October 2017

Remote-controlled aerial drones (or unmanned aerial vehicles; UAVs) are employed for surveillance by the military and police, which suggests that drone-captured footage might provide sufficient information for person identification. This study demonstrates that person identification from drone-captured images is poor when targets are unfamiliar (Experiment 1), when targets are familiar and the number of possible identities is restricted by context (Experiment 2), and when moving footage is employed (Experiment 3). Person information such as sex, race and age is also difficult to access from drone-captured footage (Experiment 4). These findings suggest that such footage provides a particularly poor medium for person identification. This is likely to reflect the sub-optimal quality of such footage, which is subject to factors such as the height and velocity at which drones fly, viewing distance, unfavourable vantage points, and ambient conditions.
Deadly acute Decompression Sickness in Risso’s dolphins
Authors: Fernández A. , Sierra E. , Díaz-Delgado J. , Sacchini S. , Sánchez-Paz Y. , Suárez-Santana C. , Arregui M. , Arbelo M. , Bernaldo de Quirós Y.
Published: October 2017

Diving air-breathing vertebrates have long been considered protected against decompression sickness (DCS) through anatomical, physiological, and behavioural adaptations. However, an acute systemic gas and fat embolic syndrome similar to DCS in human divers was described in beaked whales that stranded in temporal and spatial association with military exercises involving high-powered sonar. More recently, DCS has been diagnosed in bycaught sea turtles. Both cases were linked to human activities. Two Risso’s dolphin (Grampus griseus) out of 493 necropsied cetaceans stranded in the Canary Islands in a 16-year period (2000–2015), had a severe acute decompression sickness supported by pathological findings and gas analysis. Deadly systemic, inflammatory, infectious, or neoplastic diseases, ship collision, military sonar, fisheries interaction or other type of lethal inducing associated trauma were ruled out. Struggling with a squid during hunting is discussed as the most likely cause of DCS.
Effects of inoculants Lactobacillus brevis and Lactobacillus parafarraginis on the fermentation characteristics and microbial communities of corn stover silage
Authors: Xu Zhenshang , He Huiying , Zhang Susu , Kong Jian
Published: October 2017

To improve silage quality of crop forages, bacterial inoculants are often employed. In this study, Lactobacillus brevis SDMCC050297 and Lactobacillus parafarraginis SDMCC050300 were used as inoculants to corn stover in lab silos for ensiling. At the initial stage of ensiling, the pH value of the inoculated silages reduced more drastically, and the inoculated silages had higher lactic acid and acetic acid contents. After 20 days of ensiling, a reduction in lactic acid content coupled with an increase in acetic acid and 1,2-propanediol contents was observed in inoculated silages. Furthermore, both the amount of lactic acid bacteria and the abundance of order Lactobacillales in inoculated silages were higher than those of controls in the whole process. Meanwhile, Lb. brevis predominated before day 20 and then the dominance was shifted to Lb. parafarraginis until the late stage of ensiling. In contrast, the epiphytic Lactococcus lactic and Lb. plantarum played major roles at the beginning of naturally fermented silages and then Lb. plantarum and Lb. brevis were the most abundant at the later stage. In conclusion, these two selected strains had capability of improving the silage quality and providing the reproducible ensiling process, thus having the potential as silage inoculants.
Phosphatidylserine-Induced Conformational Modulation of Immune Cell Exhaustion-Associated Receptor TIM3
Authors: Weber Jeffrey K. , Zhou Ruhong
Published: October 2017

In the face of chronic cancers and protracted viral infections, human immune cells are known to adopt an exhausted state in which their effector functions are lost. In recent years, a number of inhibitory receptors have been connected to the immune cell exhaustion phenotype; furthermore, ligands capable of activating these receptors have been discovered. The molecular mechanisms by which these ligands affect the exhausted states of immune cells, however, are largely unknown. Here, we present the results of molecular dynamics simulations of one potential exhaustion-associated system: the complex of human inhibitory receptor TIM3 (hTIM3) and its ligand phosphatidylserine (PSF). We find that PSF fundamentally alters the electrostatic environment within hTIM3’s Ca2+ binding site, facilitating the formation of a salt bridge and freeing a tyrosine-containing strand. This liberated tyrosine then collapses into a nearby hydrophobic pocket, anchoring a modified conformational ensemble typified by a β-strand rearrangement. The “electrostatic switching/hydrophobic anchoring” mechanism of conformational modulation reported here suggests a new type of process by which TIM3 activation might be achieved. This work also highlights strategies by which PSF-mediated conformational change could be controlled, either through administration of small molecules, execution of mutations, or modification of receptor phosphorylation states.
All Dielectric Transmissive Structural Multicolor Pixel Incorporating a Resonant Grating in Hydrogenated Amorphous Silicon
Authors: Koirala Ishwor , Shrestha Vivek Raj , Park Chul-Soon , Gao Song , Lee Sang-Shin , Choi Duk-Yong
Published: October 2017

All dielectric transmissive type polarization-tuned structural multicolor pixels (MCPs) are proposed and demonstrated based on a one-dimensional hydrogenated amorphous silicon (a-Si:H) grating integrated with a silicon nitride waveguide. Both bandpass and bandstop transmission filtering characteristics in the visible regime, centered at the same wavelength, have been achieved by tailoring the structural parameters including the duty ratio of the grating and the thickness of the dielectric waveguide. For the three manufactured MCPs, the transmission peak exceeds 70% for the transverse electric (TE) polarization and 90% for the transverse magnetic (TM) polarization as observed at the resonance and off-resonance wavelength, respectively. The polarization-switched transmissions are attributed to the guided mode resonance initiated by the interaction of the a-Si:H grating and the dielectric waveguide. A broad color palette covering the entire visible band was successfully realized from a suite of MCPs with varying grating pitches. The proposed structural color pixels are expected to facilitate the construction of dynamic displays, image sensors, optical data storage, security tags, and so forth.