bluuebunny/crossref_metadata_2025 huggingface dataset:
Detection of Botulinum Toxin Muscle Effect in Humans Using Magnetic Resonance Imaging: A Qualitative Case Series
Authors: O'Dell Michael W. , Villanueva Mark , Creelman Carly , Telhan Gaurav , Nestor Jaclyn , Hentel Keith D. , Ballon Douglas , Dyke Jonathan P.
Published: May 2017

Background

Although important for dosing and dilution, there are few data describing botulinum toxin (BT) movement in human muscle.

Objective

To better understand BT movement within human muscle.

Design

Proof‐of‐concept study with descriptive case series.

Setting

Outpatient academic practice.

Participants

Five subjects with stroke who were BT naive with a mean age of 60.4 ± 14 years and time poststroke of 4.6 ± 3.7 years.

Methods

Three standardized injections were given to the lateral gastrocnemius muscle (LGM): 2 contained 25 units (U) of onabotulinumtoxinA (Botox) in 0.25 mL of saline solution and the third 0.25 mL of saline solution only. The tibialis anterior muscle (TAM) was not injected in any subject. A leg magnetic resonance image was obtained at baseline, 2 months, and 3 months later with a 3.0 Tesla Siemens scanner. Three muscles, the LGM, lateral soleus muscle (LSM), and TAM, were manually outlined on the T2 mapping sequence at each time point. A histogram of T2 relaxation times (T2‐RT) for all voxels at baseline was used to calculate a mean and standard deviation (SD) T2‐RT for each muscle. Botulinum toxin muscle effect (BTME) at 2 months and 3 months was defined as a subject‐ and muscle‐specific T2‐RT voxel threshold ≥3 SD above the baseline mean at or near BT injection sites.

Main Outcome Measures

BTME volume for each leg magnetic resonance imaging slice at 3 time points and 3 muscles for all subjects.

Results

One subject missed the 3‐month scan, leaving 18 potential observations of BTME. Little to no BTME effect was seen in the noninjected TAM. A BTME was detected in the LGM in 13 of 18 possible observations, and no effect was detected in 5 observations. Possible BTME effect was seen in the LSM in 3 subjects due to either diffusion through fascia or needle misplacement. Volume of BTME, as defined here, appeared to be substantially greater than the 0.25‐mL injection volume.

Conclusions

This descriptive case series is among the first attempts to quantify BTME within human muscle. Our findings are preliminary and are limited by a few inconsistencies. However, we conclude that use of magnetic resonance imaging to detect the volume of BTME is feasible and may assist researchers in modeling the spread and diffusion of BT within human muscle.

Level of Evidence

IV
Genera of phytopathogenic fungi: GOPHY 1
Authors: Marin-Felix Y. , Groenewald J.Z. , Cai L. , Chen Q. , Marincowitz S. , Barnes I. , Bensch K. , Braun U. , Camporesi E. , Damm U. , de Beer Z.W. , Dissanayake A. , Edwards J. , Giraldo A. , Hernández-Restrepo M. , Hyde K.D. , Jayawardena R.S. , Lombard L. , Luangsa-ard J. , McTaggart A.R. , Rossman A.Y. , Sandoval-Denis M. , Shen M. , Shivas R.G. , Tan Y.P. , van der Linde E.J. , Wingfield M.J. , Wood A.R. , Zhang J.Q. , Zhang Y. , Crous P.W.
Published: May 2017

Genera of Phytopathogenic Fungi (GOPHY) is introduced as a new series of publications in order to provide a stable platform for the taxonomy of phytopathogenic fungi. This first paper focuses on 21 genera of phytopathogenic fungi:Bipolaris,Boeremia,Calonectria,Ceratocystis,Cladosporium,Colletotrichum,Coniella,Curvularia,Monilinia,Neofabraea,Neofusicoccum,Pilidium,Pleiochaeta,Plenodomus,Protostegia,Pseudopyricularia,Puccinia,Saccharata,Thyrostroma,VenturiaandWilsonomyces. For each genus, a morphological description and information about its pathology, distribution, hosts and disease symptoms are provided. In addition, this information is linked to primary and secondary DNA barcodes of the presently accepted species, and relevant literature. Moreover, several novelties are introduced, i.e. new genera, species and combinations, and neo-, lecto- and epitypes designated to provide a stable taxonomy. This first paper includes one new genus, 26 new species, ten new combinations, and four typifications of older names.
PATTERNS OF WEANING AMONG ANCESTRAL HURON-WENDAT COMMUNITIES, DETERMINED FROM NITROGEN ISOTOPES
Authors: Pfeiffer Susan , Sealy Judith C. , Williamson Ronald F. , Forrest Crystal , Lesage Louis
Published: May 2017

Archaeological evidence of the ancestral Huron-Wendat Nation of Southern Ontario, Canada, shows a population increase from the thirteenth through sixteenth centuries, suggesting high fertility. Birth timing and infant survival are influenced by mothers' decisions about weaning. This study explores trophic enrichment of δ15N in horizontal dentine slices from 35 deciduous molars (n= 33 dm1,n= 2 dm2) and 39 permanent first molars (M1) representing five Huron-Wendat ossuaries, dating from the fourteenth through seventeenth centuries. Weaning was normally incomplete at the end of dm formation, at an age of about 2.5 years. Post-weaning dentine values appear by the end of crown formation of M1. The weaning process began between 8 and 18 months and was complete in all cases by 3.5 years. Timing of the weaning process does not support the idea that Huron-Wendat population increase was associated with early weaning of infants. Communities from the sixteenth century and thereafter show earlier completion of weaning. Reasons for earlier cessation of breastfeeding may be found in the social and biological disruptions of the era of European contact. Values from permanent teeth of mandibles with sex attributed suggest a more homogeneous, possibly venison-oriented, post-weaning diet among males.
REVISITING HOGUP CAVE, UTAH: INSIGHTS FROM NEW RADIOCARBON DATES AND STRATIGRAPHIC ANALYSIS
Authors: Martin Erik P. , Coltrain Joan Brenner , Codding Brian F.
Published: May 2017

The remarkable finds from the trans-Holocene archaeological record excavated at Hogup Cave, Utah, helped define our understanding of Great Basin prehistory. However, many scholars doubt the integrity of the site's depositional sequence and resulting chronological interpretations. To resolve these concerns, we produce several Bayesian chronological models combining 14 new radiocarbon dates with the results of past dating efforts. We first present an examination of the excavation and previously derived dates, finding that several of the most anomalous dates can be accounted for by details in the excavation's field notes. We then report our new dates and construct an initial Bayesian chronological model to serve as a framework for three increasingly complex models synthesizing old and new dates from the site. The best-supported model divides the site's stratigraphy into four occupational phases: Strata 1 through 7 (9790 to 6490 cal B.P.), Stratum 8 (5840 to 3330 cal B.P.), Strata 9 and 10 (2870 to 2760 cal B.P.), and Strata 11 through 16 (2610 to 360 cal B.P.). This result raises several questions to direct future research and dating efforts at Hogup Cave and serves as a model for reevaluating complex stratigraphic sequences in western North America and beyond.
A BIRD'S-EYE VIEW OF PROTO-TEWA SUBSISTENCE AGRICULTURE: MAKING THE CASE FOR FLOODPLAIN FARMING IN THE OHKAY OWINGEH HOMELAND, NEW MEXICO
Authors: Eiselt B. Sunday , Darling J. Andrew , Duwe Samuel , Willis Mark , Walker Chester , Hudspeth William , Reeder-Meyers Leslie
Published: May 2017

Previous research on agriculture in the American Southwest focuses overwhelmingly on archaeological survey methods to discern surface agricultural features, which, in combination with climatological, geological, and geographical variables, are used to create models about agricultural productivity in the past. However, with few exceptions, the role of floodplain irrigation and floodwater farming in ancestral Pueblo agriculture is generally downplayed in scholarly discourse. Using a variety of methods, including Unmanned Aerial Vehicles (UAV), satellite imagery, pedestrian survey, and supervised classification of remotely sensed imagery, we examine this issue through a consideration of how ancestral Ohkay Owingeh (Tewa) people solved the challenges of arid land farming in the lower Rio Chama watershed of New Mexico during the Classic period (A.D. 1350–1598). Based on acreage estimates, our results indicate that runoff and rainwater fields in terrace environments would have been insufficient to supply the nutritional needs of an ancestral Tewa population exceeding 10,000 individuals. Based on these observations, we present a case for the substantial role of subsistence agriculture in the floodplain of the Rio Chama and its associated tributaries.
Large-eddy simulation of flow over a cylinder with from to : a skin-friction perspective
Authors: Cheng W. , Pullin D. I. , Samtaney R. , Zhang W. , Gao W.
Published: May 2017

We present wall-resolved large-eddy simulations (LES) of flow over a smooth-wall circular cylinder up to$Re_{D}=8.5\times 10^{5}$, where$Re_{D}$is Reynolds number based on the cylinder diameter$D$and the free-stream speed$U_{\infty }$. The stretched-vortex subgrid-scale (SGS) model is used in the entire simulation domain. For the sub-critical regime, six cases are implemented with$3.9\times 10^{3}\leqslant Re_{D}\leqslant 10^{5}$. Results are compared with experimental data for both the wall-pressure-coefficient distribution on the cylinder surface, which dominates the drag coefficient, and the skin-friction coefficient, which clearly correlates with the separation behaviour. In the super-critical regime, LES for three values of$Re_{D}$are carried out at different resolutions. The drag-crisis phenomenon is well captured. For lower resolution, numerical discretization fluctuations are sufficient to stimulate transition, while for higher resolution, an applied boundary-layer perturbation is found to be necessary to stimulate transition. Large-eddy simulation results at$Re_{D}=8.5\times 10^{5}$, with a mesh of$8192\times 1024\times 256$, agree well with the classic experimental measurements of Achenbach (J. Fluid Mech., vol. 34, 1968, pp. 625–639) especially for the skin-friction coefficient, where a spike is produced by the laminar–turbulent transition on the top of a prior separation bubble. We document the properties of the attached-flow boundary layer on the cylinder surface as these vary with$Re_{D}$. Within the separated portion of the flow, mean-flow separation–reattachment bubbles are observed at some values of$Re_{D}$, with separation characteristics that are consistent with experimental observations. Time sequences of instantaneous surface portraits of vector skin-friction trajectory fields indicate that the unsteady counterpart of a mean-flow separation–reattachment bubble corresponds to the formation of local flow-reattachment cells, visible as coherent bundles of diverging surface streamlines.
Spatial structure of shock formation
Authors: Eggers J. , Grava T. , Herrada M. A. , Pitton G.
Published: May 2017

The formation of a singularity in a compressible gas, as described by the Euler equation, is characterized by the steepening and eventual overturning of a wave. Using self-similar variables in two space dimensions and a power series expansion based on powers of $|t_{0}-t|^{1/2}$, $t_{0}$ being the singularity time, we show that the spatial structure of this process, which starts at a point, is equivalent to the formation of a caustic, i.e. to a cusp catastrophe. The lines along which the profile has infinite slope correspond to the caustic lines, from which we construct the position of the shock. By solving the similarity equation, we obtain a complete local description of wave steepening and of the spreading of the shock from a point. The shock spreads in the transversal direction as $|t_{0}-t|^{1/2}$ and in the direction of propagation as $|t_{0}-t|^{3/2}$, as also found in a one-dimensional model problem.
Open Access…with a Twist! – Canadian Edition
Authors: Poulin Sonia
Published: May 2017

The presentation delivered in Oxford during IALL's 35th Annual Course on Law and Legal Information offered my perspective on Open Access to legal information within the context of Access to Justice in Canada. Please find below an overview of my presentation.
Diversities Among Common Law Countries
Authors: Reynolds Francis
Published: May 2017

My purpose is to provide a survey indicating some of the differences within the common law between one country and another. I must immediately make clear that there is at least one person, perhaps several, in this room (including the other speakers) who know very much more about any one of the topics I shall consider than I claim to do. I hope that they will excuse me for any inaccuracies or lapses of understanding in their own areas: my only purpose is to make general observations on the diversities between common law countries as I see them.
Templates as the interaction of recursive word structure and prosodic well-formedness
Authors: Guekguezian Peter Ara
Published: May 2017

Templatic morphology involves the appearance of a fixed shape on a morpheme in a specific morphological context. This paper makes two claims: the morphological context of a template is syntactically cyclic, resulting in recursive prosodic word structure, and the shape of a template results from prosodic well-formedness conditions on the internal prosodic word. Templatic morphology in Chukchansi Yokuts illustrates these claims: affixes that trigger templates transfer the root to the phonology before other material is transferred, so that the root forms a prosodic word which is internal to the whole word. Roots with one underlying vowel are augmented to meet a disyllabic minimality requirement on prosodic words; the resulting disyllable forms a light–heavy iamb, to optimally satisfy Chukchansi parsing requirements. Templatic morphology falls out from the predictable interaction of the syntax–phonology interface and general phonological properties of a language, and needs no special apparatus or diacritics.
A survey of structure from motion.
Authors: Özyeşil Onur , Voroninski Vladislav , Basri Ronen , Singer Amit
Published: May 2017

The structure from motion (SfM) problem in computer vision is to recover the three-dimensional (3D) structure of a stationary scene from a set of projective measurements, represented as a collection of two-dimensional (2D) images, via estimation of motion of the cameras corresponding to these images. In essence, SfM involves the three main stages of (i) extracting features in images (e.g. points of interest, lines,etc.) and matching these features between images, (ii) camera motion estimation (e.g. using relative pairwise camera positions estimated from the extracted features), and (iii) recovery of the 3D structure using the estimated motion and features (e.g. by minimizing the so-calledreprojection error). This survey mainly focuses on relatively recent developments in the literature pertaining to stages (ii) and (iii). More specifically, after touching upon the early factorization-based techniques for motion and structure estimation, we provide a detailed account of some of the recent cameralocationestimation methods in the literature, followed by discussion of notable techniques for 3D structure recovery. We also cover the basics of thesimultaneous localization and mapping(SLAM) problem, which can be viewed as a specific case of the SfM problem. Further, our survey includes a review of the fundamentals of feature extraction and matching (i.e. stage (i) above), various recent methods for handling ambiguities in 3D scenes, SfM techniques involving relatively uncommon camera models and image features, and popular sources of data and SfM software.
Algebraic multigrid methods
Authors: Xu Jinchao , Zikatanov Ludmil
Published: May 2017

This paper provides an overview of AMG methods for solving large-scale systems of equations, such as those from discretizations of partial differential equations. AMG is often understood as the acronym of ‘algebraic multigrid’, but it can also be understood as ‘abstract multigrid’. Indeed, we demonstrate in this paper how and why an algebraic multigrid method can be better understood at a more abstract level. In the literature, there are many different algebraic multigrid methods that have been developed from different perspectives. In this paper we try to develop a unified framework and theory that can be used to derive and analyse different algebraic multigrid methods in a coherent manner. Given a smoother$R$for a matrix$A$, such as Gauss–Seidel or Jacobi, we prove that the optimal coarse space of dimension$n_{c}$is the span of the eigenvectors corresponding to the first$n_{c}$eigenvectors$\bar{R}A$(with$\bar{R}=R+R^{T}-R^{T}AR$). We also prove that this optimal coarse space can be obtained via a constrained trace-minimization problem for a matrix associated with$\bar{R}A$, and demonstrate that coarse spaces of most existing AMG methods can be viewed as approximate solutions of this trace-minimization problem. Furthermore, we provide a general approach to the construction of quasi-optimal coarse spaces, and we prove that under appropriate assumptions the resulting two-level AMG method for the underlying linear system converges uniformly with respect to the size of the problem, the coefficient variation and the anisotropy. Our theory applies to most existing multigrid methods, including the standard geometric multigrid method, classical AMG, energy-minimization AMG, unsmoothed and smoothed aggregation AMG and spectral AMGe.
FREEDOM OR CONSTRAINT: THE SPEEDING BICYCLE AND THE INDUSTRIAL SUBJECT IN H. G. WELLS'STHE WHEELS OF CHANCE
Authors: Chen Eva
Published: May 2017

In this passage,quoted fromGrant Allen's 1897 bestsellerThe Type-writer Girl, the New-Woman-turned-typist Juliet Appleton decides to quit typing in a London law office where she is forced to “click, click, click all day like a machine.” As an alternative and a release, she jumps on her bicycle and rides for an “idyllic” anarchic farm in the countryside (11). There across the Weald of Sussex and Surrey, the bicycling Juliet encounters two other forms of mobility, that of the train and the horse-driven carriage. The train, an icon of industrial modernity that “annihilated time and space” (Schivelbusch 36), rumbles brutally over the green fields and terrifies the horses, which are symbols of a natural, organic, preindustrial world. But Juliet's bicycle seems to create a balance between the two worlds. The bicycle as the never-failing steel horse enables her to utilize the achievements of industrial mechanization and also allows for a degree of freedom and human agency. Juliet is portrayed as a true modern heroine and an “unabashed” daughter of the industrial age, because she seems to possess a new subjectivity bred and made possible by the partnership between machine and nature, mechanical power and organic energy.
Village democracy and household welfare: evidence from rural China
Authors: Xu Ying , Amacher Gregory S. , Xu Jintao
Published: May 2017

Village democratization in rural China is found to have profound impacts on many socio-economic aspects, but little is understood as to how welfare impacts may occur through farmers' principal production activities. This study helps to fill this gap by investigating how village democracy affects rural household welfare through these channels, using a unique household survey. The authors first establish a theoretical framework that links democracy to household welfare through changes in production efficiency. Focusing on both agricultural and forest production, they then implement empirical estimation using stochastic production frontier techniques with careful consideration of household heterogeneity in technical efficiency. They find that higher levels of village democracy significantly increase farmers' production efficiency, thereby improving their welfare. To the authors' knowledge, this is the first study on the impacts of democracy on producer welfare using micro-level data.
Kantian Phenomenalism Without Berkeleyan Idealism
Authors: Jankowiak Tim
Published: May 2017

Phenomenalist interpretations of Kant are out of fashion. The most common complaint from anti-phenomenalist critics is that a phenomenalist reading of Kant would collapse Kantian idealism into Berkeleyan idealism. This would be unacceptable because Berkeleyan idealism is incompatible with core elements of Kant’s empirical realism. In this paper, I argue that not all phenomenalist readings threaten empirical realism. First, I distinguish several variants of phenomenalism, and then show that Berkeley’s idealism is characterized by his commitment to most of them. I then make the case that two forms of phenomenalism are consistent with Kant’s empirical realism. The comparison between Kant and Berkeley runs throughout the paper, with special emphasis on the significance of their theories of intentionality.
Dental politics and subsidy systems for adults in Sweden from 1974 until 2016
Authors: Franzon Bengt , Axtelius Björn , Åkerman Sigvard , Klinge Björn
Published: May 2017

Aims:

The dental health sector, as part of the Swedish welfare system, originated in 1974. Since then, the dental insurance has undergone three major changes. The aim of this archive study was to study where in the legislative process the dental politics concerning national dental insurance and subsidies were formed.

Materials and Methods:

The material, such as Commission of inquiry proposals and Government Bills from four major dental reforms, was collected from the library at the Sveriges Riksdag (Swedish Parliament) and was analysed and structured using a modified version of the Health Field Model.

Results:

The views on the fundamental ideas, such as the connection between general and dental health, preventive dentistry, rehabilitation of the mouth and promotion of dental health, were the same over the years. The views on dentistry as a market, when it comes to freedom of prices, have undergone a major change since 1974, but the view on the welfare state remains the same.

Conclusions:

The Swedish dental subsidy systems and how dentistry has been treated politically are the results of a chain of events ranging from care for the population's dental health, political doctrines, ‘zeitgeist‚, dental policy, to state finances.
Single-cell RNA-seq enables comprehensive tumour and immune cell profiling in primary breast cancer
Authors: Chung Woosung , Eum Hye Hyeon , Lee Hae-Ock , Lee Kyung-Min , Lee Han-Byoel , Kim Kyu-Tae , Ryu Han Suk , Kim Sangmin , Lee Jeong Eon , Park Yeon Hee , Kan Zhengyan , Han Wonshik , Park Woong-Yang
Published: May 2017

Single-cell transcriptome profiling of tumour tissue isolates allows the characterization of heterogeneous tumour cells along with neighbouring stromal and immune cells. Here we adopt this powerful approach to breast cancer and analyse 515 cells from 11 patients. Inferred copy number variations from the single-cell RNA-seq data separate carcinoma cells from non-cancer cells. At a single-cell resolution, carcinoma cells display common signatures within the tumour as well as intratumoral heterogeneity regarding breast cancer subtype and crucial cancer-related pathways. Most of the non-cancer cells are immune cells, with three distinct clusters of T lymphocytes, B lymphocytes and macrophages. T lymphocytes and macrophages both display immunosuppressive characteristics: T cells with a regulatory or an exhausted phenotype and macrophages with an M2 phenotype. These results illustrate that the breast cancer transcriptome has a wide range of intratumoral heterogeneity, which is shaped by the tumour cells and immune cells in the surrounding microenvironment.
The molecular mechanism of the type IVa pilus motors
Authors: McCallum Matthew , Tammam Stephanie , Khan Ahmad , Burrows Lori L. , Howell P. Lynne
Published: May 2017

Type IVa pili are protein filaments essential for virulence in many bacterial pathogens; they extend and retract from the surface of bacterial cells to pull the bacteria forward. The motor ATPase PilB powers pilus assembly. Here we report the structures of the core ATPase domains of Geobacter metallireducens PilB bound to ADP and the non-hydrolysable ATP analogue, AMP-PNP, at 3.4 and 2.3 Å resolution, respectively. These structures reveal important differences in nucleotide binding between chains. Analysis of these differences reveals the sequential turnover of nucleotide, and the corresponding domain movements. Our data suggest a clockwise rotation of the central sub-pores of PilB, which through interactions with PilC, would support the assembly of a right-handed helical pilus. Our analysis also suggests a counterclockwise rotation of the C2 symmetric PilT that would enable right-handed pilus disassembly. The proposed model provides insight into how this family of ATPases can power pilus extension and retraction.
Quantification of differential gene expression by multiplexed targeted resequencing of cDNA
Authors: Arts Peer , van der Raadt Jori , van Gestel Sebastianus H.C. , Steehouwer Marloes , Shendure Jay , Hoischen Alexander , Albers Cornelis A.
Published: May 2017

Whole-transcriptome or RNA sequencing (RNA-Seq) is a powerful and versatile tool for functional analysis of different types of RNA molecules, but sample reagent and sequencing cost can be prohibitive for hypothesis-driven studies where the aim is to quantify differential expression of a limited number of genes. Here we present an approach for quantification of differential mRNA expression by targeted resequencing of complementary DNA using single-molecule molecular inversion probes (cDNA-smMIPs) that enable highly multiplexed resequencing of cDNA target regions of ∼100 nucleotides and counting of individual molecules. We show that accurate estimates of differential expression can be obtained from molecule counts for hundreds of smMIPs per reaction and that smMIPs are also suitable for quantification of relative gene expression and allele-specific expression. Compared with low-coverage RNA-Seq and a hybridization-based targeted RNA-Seq method, cDNA-smMIPs are a cost-effective high-throughput tool for hypothesis-driven expression analysis in large numbers of genes (10 to 500) and samples (hundreds to thousands).
Beta-agonist overuse and delay in obtaining medical review in high risk asthma: a secondary analysis of data from a randomised controlled trial
Authors: Pilcher Janine , Patel Mitesh , Pritchard Alison , Thayabaran Darmiga , Ebmeier Stefan , Shaw Dominick , Black Peter , Braithwaite Irene , Weatherall Mark , Beasley Richard
Published: May 2017

Asthma mortality surveys report delays in seeking medical review and overuse of beta-agonist therapy as factors contributing to a fatal outcome. However, the strength of these associations is limited because many asthma deaths are unwitnessed. We undertook a secondary analysis of data from a 24-week randomised controlled trial of 303 patients with high-risk asthma, randomised to combination budesonide/formoterol inhaler according to a single maintenance and reliever therapy regimen or fixed dose budesonide/formoterol with salbutamol as reliever (Standard) regimen. Medication use was measured by electronic monitors. The thresholds for high, marked and extreme beta-agonist use days were defined in the single maintenance and reliever therapy arm as: >8, >12 and >16 actuations of budesonide/formoterol in excess of four maintenance doses, respectively; and in the Standard arm as: >16, >24 and >32 actuations of salbutamol, respectively. Whether a medical review was obtained within 48 h of an overuse episode was determined by review of data collected during the study by participant report. The mean (standard deviation) proportion of days in which high, marked and extreme beta-agonist overuse occurred without medical review within 48 h was 0·94(0·20), 0·94(0·15) and 0·94(0·17), and 0·92(0·19), 0·90(0·26) and 0·94(0·15) for single maintenance and reliever therapy and Standard regimens, respectively. In at least 90% of days, in which beta-agonist overuse occurred, patients did not obtain medical review within 48 h of beta-agonist overuse, regardless of the magnitude of overuse or the inhaled corticosteroid/long-acting beta-agonist regimen.
Raman spectroscopy and regenerative medicine: a review
Authors: Ember Katherine J. I. , Hoeve Marieke A. , McAughtrie Sarah L. , Bergholt Mads S. , Dwyer Benjamin J. , Stevens Molly M. , Faulds Karen , Forbes Stuart J. , Campbell Colin J.
Published: May 2017

The field of regenerative medicine spans a wide area of the biomedical landscape—from single cell culture in laboratories to human whole-organ transplantation. To ensure that research is transferrable from bench to bedside, it is critical that we are able to assess regenerative processes in cells, tissues, organs and patients at a biochemical level. Regeneration relies on a large number of biological factors, which can be perturbed using conventional bioanalytical techniques. A versatile, non-invasive, non-destructive technique for biochemical analysis would be invaluable for the study of regeneration; and Raman spectroscopy is a potential solution. Raman spectroscopy is an analytical method by which chemical data are obtained through the inelastic scattering of light. Since its discovery in the 1920s, physicists and chemists have used Raman scattering to investigate the chemical composition of a vast range of both liquid and solid materials. However, only in the last two decades has this form of spectroscopy been employed in biomedical research. Particularly relevant to regenerative medicine are recent studies illustrating its ability to characterise and discriminate between healthy and disease states in cells, tissue biopsies and in patients. This review will briefly outline the principles behind Raman spectroscopy and its variants, describe key examples of its applications to biomedicine, and consider areas of regenerative medicine that would benefit from this non-invasive bioanalytical tool.
Serum sonic hedgehog (SHH) and interleukin-(IL-6) as dual prognostic biomarkers in progressive metastatic breast cancer
Authors: Noman A. S. , Uddin M. , Chowdhury A. A. , Nayeem M. J. , Raihan Z. , Rashid M. I. , Azad A. K. , Rahman M. L. , Barua D. , Sultana A. , Shirin A. , Ferdous J. , Parag R. R. , Rahman S. M. , Mahmud M. R. , Jerin C. S. , Jahan N. , Siddiqua A. , Ara T. , Sabur E. B. , Alam S. S. , Baidya S. , Akther S. , Rahman M. Z. , Banu T. , Murugan A. K. , Sabri S. , Islam S. M. S. , Karakas B. , Aboussekhra A. , Yeger H. , Farhat W. A. , Islam S. S.
Published: May 2017

Serum from one hundred and ten breast cancer patients and thirty healthy female volunteers, were prospectively collected and evaluated for serum levels of Shh and IL-6 using human Shh and IL-6 specific enzyme-linked immunoassays. All patients were regularly monitored for event free survival (EFS) and overall survival (OS). Overall outcome analysis was based on serum Shh and IL-6 levels. In patients with progressive metastatic BC, both serum Shh and IL-6 concentrations were elevated in 44% (29 of 65) and 63% (41 of 65) of patients, respectively, at a statistically significant level [Shh (p = 0.0001) and IL-6 (p = 0.0001)] compared to the low levels in healthy volunteers. Serum levels tended to increase with metastatic progression and lymph node positivity. High serum Shh and IL-6 levels were associated with poor EFS and OS opposite to the negative or lower levels in serum Shh and IL-6. The elevated levels of both serum Shh and IL-6 were mainly observed in BC patients who had a significantly higher risk of early recurrence and bone metastasis, and associated with a worse survival for patients with progressive metastatic BC. Further studies are warranted for validating these biomarkers as prognostic tools in a larger patient cohort and in a longer follow-up study.
A Systems Genetics Approach Identified GPD1L and its Molecular Mechanism for Obesity in Human Adipose Tissue
Authors: He Hao , Sun Dianjianyi , Zeng Yong , Wang Ruifeng , Zhu Wei , Cao Shaolong , Bray George A. , Chen Wei , Shen Hui , Sacks Frank M. , Qi Lu , Deng Hong-wen
Published: May 2017

To explore novel molecular mechanisms underlying obesity, we applied a systems genetics framework to integrate risk genetic loci from the largest body mass index (BMI) genome-wide association studies (GWAS) meta-analysis with mRNA and microRNA profiling in adipose tissue from 200 subjects. One module was identified to be most significantly associated with obesity and other metabolic traits. We identified eight hub genes which likely play important roles in obesity metabolism and identified microRNAs that significantly negatively correlated with hub genes. This module was preserved in other three test gene expression datasets, and all hub genes were consistently downregulated in obese subjects through the meta-analysis. Gene GPD1L had the highest connectivity and was identified a key causal regulator in the module. Gene GPD1L was significantly negatively correlated with the expression of miR-210, which was experimentally validated that miR-210 regulated GPD1L protein level through direct interaction with its mRNA three prime untranslated region (3′-UTR). GPD1L was found to be upregulated during weight loss and weight maintenance induced by low calorie diet (LCD), while downregulated during weight gain induced by high-fat diet (HFD). The results indicated that increased GPD1L in adipose tissue may have a significant therapeutic potential in reducing obesity and insulin resistance.
Young children copy cumulative technological design in the absence of action information
Authors: Reindl E. , Apperly I. A. , Beck S. R. , Tennie C.
Published: May 2017

The ratchet effect – the accumulation of beneficial changes in cultural products beyond a level that individuals could reach on their own – is a topic of increasing interest. It is currently debated which social learning mechanisms allow for the generation and transmission of cumulative culture. This study focused on transmission, investigating whether 4- to 6-year-old children were able to copy cumulative technological design and whether they could do so without action information (emulation). We adapted the spaghetti tower task, previously used to test for accumulation of culture in human adults. A baseline condition established that the demonstrated tower design was beyond the innovation skills of individual children this age and so represented a culture-dependent product for them. There were 2 demonstration conditions: a full demonstration (actions plus (end-)results) and an endstate- demonstration (end-results only). Children in both demonstration conditions built taller towers than those in the baseline. Crucially, in both demonstration conditions some children also copied the demonstrated tower. We provide the first evidence that young children learn from, and that some of them even copy, cumulative technological design, and that – in line with some adult studies – action information is not always necessary to transmit culture-dependent traits.
Zooplankton Community Profiling in a Eutrophic Freshwater Ecosystem-Lake Tai Basin by DNA Metabarcoding
Authors: Yang Jianghua , Zhang Xiaowei , Xie Yuwei , Song Chao , Zhang Yong , Yu Hongxia , Burton G. Allen
Published: May 2017

Communities of zooplankton, a critical portion of aquatic ecosystems, can be adversely affected by contamination resulting from human activities. Understanding the influence of environmental change on zooplankton communities under field-conditions is hindered by traditional labor-intensive approaches that are prone to taxonomic and enumeration mistakes. Here, metabarcoding of cytochrome c oxidase I (COI) region of mitochondrial DNA was used to characterize the genetic diversity of zooplankton. The species composition of zooplankton communities determined by metabarcoding was consistent with the results based on the traditional morphological approach. The spatial distribution of common species (frequency of occurrence >10 samples) by metabarcoding exhibited good agreement with morphological data. Furthermore, metabarcoding can clearly distinguish the composition of the zooplankton community between lake and river ecosystems. In general, rotifers were more abundant in riverine environments than lakes and reservoirs. Finally, the sequence read number of different taxonomic groups using metabarcoding was positively correlated with the zooplankton biomass inferred by density and body length of zooplankton. Overall, the utility of metabarcoding for taxonomic profiling of zooplankton communities was validated by the morphology-based method on a large ecological scale. Metabarcoding of COI could be a powerful and efficient biomonitoring tool to protect local aquatic ecosystems.
Heterologous expression and characterization of functional mushroom tyrosinase (AbPPO4)
Authors: Pretzler Matthias , Bijelic Aleksandar , Rompel Annette
Published: May 2017

Tyrosinases are an ubiquitous group of copper containing metalloenzymes that hydroxylate and oxidize phenolic molecules. In an application context the term ‘tyrosinase’ usually refers to ‘mushroom tyrosinase’ consisting of a mixture of isoenzymes and containing a number of enzymatic side-activities. We describe a protocol for the efficient heterologous production of tyrosinase 4 from Agaricus bisporus in Escherichia coli. Applying this procedure a pure preparation of a single isoform of latent tyrosinase can be achieved at a yield of 140 mg per liter of autoinducing culture medium. This recombinant protein possesses the same fold as the enzyme purified from the natural source as evidenced by single crystal X-ray diffraction. The latent enzyme can be activated by limited proteolysis with proteinase K which cleaves the polypeptide chain after K382, only one The latent enzyme can amino acid before the main in-vivo activation site. Latent tyrosinase can be used as obtained and enzymatic activity may be induced in the reaction mixture by the addition of an ionic detergent (e.g. 2 mM SDS). The proteolytically activated mushroom tyrosinase shows >50% of its maximal activity in the range of pH 5 to 10 and accepts a wide range of substrates including mono- and diphenols, flavonols and chalcones.
The Impact of a Severe Drought on Dust Lifting in California’s Owens Lake Area
Authors: Borlina Cauê S. , Rennó Nilton O.
Published: May 2017

Mineral dust aerosols are responsible for some of the largest sources of uncertainties in our current understanding of climate change. Here we show that a severe drought is having a significant impact in one of largest sources of mineral dust aerosols of the U.S., the Owens Lake area in California’s southwest. Measurements of aerosol concentration (PM2.5 particle matter) in the Owens Lake salty playa show that the annual mean concentration of PM2.5 aerosol has been increasing steadily since the beginning of the current drought, with periods of high aerosol concentration increasing from 4 months in 2013 to 9 months in 2015. Interestingly, the PM2.5 aerosol concentration usually increases abruptly from less than ~0.05 mg/m3 to ~0.25 mg/m3. This occurs when saltation events break salt crusts produced by the efflorescence of brine in the salty playa. The brine is produced by either rainfall or runoff water. Based on this observation, we hypothesize that there is an upper limit of ~0.25 mg/m3 in the annual mean PM2.5 aerosols concentration in the Owens Lake basin that might limit the impact of mineral dust aerosols on climate. Indeed, the upper annual limit of ~0.25 mg/m3 has been nearly reached during the current drought.
Establishment of a Strong Link Between Smoking and Cancer Pathogenesis through DNA Methylation Analysis
Authors: Ma Yunlong , Li Ming D.
Published: May 2017

Smoking is a well-documented risk factor in various cancers, especially lung cancer. In the current study, we tested the hypothesis that abnormal DNAm loci associated with smoking are enriched in genes and pathways that convey a risk of cancer by determining whether smoking-related methylated genes led to enrichment in cancer-related pathways. We analyzed two sets of smoking-related methylated genes from 28 studies originating from blood and buccal samples. By analyzing 320 methylated genes from 26 studies on blood samples (N = 17,675), we found 57 enriched pathways associated with different types of cancer (FDR < 0.05). Of these, 11 were also significantly overrepresented in the 661 methylated genes from two studies of buccal samples (N = 1,002). We further found the aryl hydrocarbon receptor signaling pathway plays an important role in the initiation of smoking-attributable cancer. Finally, we constructed a subnetwork of genes important for smoking-attributable cancer from the 48 non-redundant genes in the 11 oncogenic pathways. Of these, genes such as DUSP4 and AKT3 are well documented as being involved in smoking-related lung cancer. In summary, our findings provide robust and systematic evidence in support of smoking’s impact on the epigenome, which may be an important contributor to cancer.
The caterpillar fungus, Ophiocordyceps sinensis, genome provides insights into highland adaptation of fungal pathogenicity
Authors: Xia En-Hua , Yang Da-Rong , Jiang Jian-Jun , Zhang Qun-Jie , Liu Yuan , Liu Yun-Long , Zhang Yun , Zhang Hai-Bin , Shi Cong , Tong Yan , Kim Changhoon , Chen Hua , Peng Yan-Qiong , Yu Yue , Zhang Wei , Eichler Evan E. , Gao Li-Zhi
Published: May 2017

To understand the potential genetic basis of highland adaptation of fungal pathogenicity, we present here the ~116 Mb de novo assembled high-quality genome of Ophiocordyceps sinensis endemic to the Qinghai-Tibetan Plateau. Compared with other plain-dwelling fungi, we find about 3.4-fold inflation of the O. sinensis genome due to a rapid amplification of long terminal repeat retrotransposons that occurred ~38 million years ago in concert with the uplift of the plateau. We also observe massive removal of thousands of genes related to the transport process and energy metabolism. O. sinensis displays considerable lineage-specific expansion of gene families functionally enriched in the adaptability of low-temperature of cold tolerance, fungal pathogenicity and specialized host infection. We detect signals of positive selection for genes involved in peroxidase and hypoxia to enable its highland adaptation. Resequencing and analyzing 31 whole genomes of O. sinensis, representing nearly all of its geographic range, exhibits latitude-based population divergence and nature selection for population inhabitation towards higher altitudes on the Qinghai-Tibetan Plateau.
Long non-coding RNA PARTICLE bridges histone and DNA methylation
Authors: O’Leary Valerie Bríd , Hain Sarah , Maugg Doris , Smida Jan , Azimzadeh Omid , Tapio Soile , Ovsepian Saak Victor , Atkinson Michael John
Published: May 2017

PARTICLE (Gene PARTICL- ‘Promoter of MAT2A-Antisense RadiaTion Induced Circulating LncRNA) expression is transiently elevated following low dose irradiation typically encountered in the workplace and from natural sources. This long non-coding RNA recruits epigenetic silencers for cis-acting repression of its neighbouring Methionine adenosyltransferase 2A gene. It now emerges that PARTICLE operates as a trans-acting mediator of DNA and histone lysine methylation. Chromatin immunoprecipitation sequencing (ChIP-seq) and immunological evidence established elevated PARTICLE expression linked to increased histone 3 lysine 27 trimethylation. Live-imaging of dbroccoli-PARTICLE revealing its dynamic association with DNA methyltransferase 1 was confirmed by flow cytometry, immunoprecipitation and direct competitive binding interaction through electrophoretic mobility shift assay. Acting as a regulatory docking platform, the long non-coding RNA PARTICLE serves to interlink epigenetic modification machineries and represents a compelling innovative component necessary for gene silencing on a global scale.
Antinociceptive effects of caloric restriction on post-incisional pain in nonobese rats
Authors: Liu Yue , Ni Yuan , Zhang Wei , Sun Yu-E , Ma Zhengliang , Gu Xiaoping
Published: May 2017

Caloric restriction (CR) increases lifespan, retards physiological signs of aging, and delays a variety of diseases. Reduction of inflammatory response was proposed as one of the molecular mechanisms for how CR exerts beneficial effects. The present study investigated the effects of CR on postoperative pain in rats. Adult nonobese rats were divided into two dietary groups, an ad libitum fed group (AL) and a caloric restriction group (CR) that was provided with 60% of the food intake of AL rats. After 6 weeks, the effects of CR on pain behaviors and inflammation induced by plantar incision were examined. CR rats displayed significantly reduced nonevoked pain, mechanical allodynia and thermal hyperalgesia induced by incision, and showed decreased levels of pro-inflammatory cytokines in serum, peri-incisional skin tissue and ipsilateral spinal cord dorsal horn at 6 h and 24 h after incision. The analgesic efficiency of parecoxib and morphine, two agents widely used for the management of postoperative pain clinically, was reinforced by CR. Together, CR generates antinociceptive effects on postoperative incisional pain in rats, perhaps providing some improvement of QOL in patients with postoperative pain, and the beneficial effects may be attributable to the inhibition of excessive inflammation induced by surgical injury.
Altered balance of excitatory and inhibitory learning in a genetically modified mouse model of glutamatergic dysfunction relevant to schizophrenia
Authors: Sanderson David J. , Lee Aletheia , Sprengel Rolf , Seeburg Peter H. , Harrison Paul J. , Bannerman David M.
Published: May 2017

The GluA1 AMPAR subunit (encoded by the Gria1 gene) has been implicated in schizophrenia. Gria1 knockout in mice results in recently experienced stimuli acquiring aberrantly high salience. This suggests that GluA1 may be important for learning that is sensitive to the temporal contiguity between events. To test this, mice were trained on a Pavlovian trace conditioning procedure in which the presentation of an auditory cue and food were separated by a temporal interval. Wild-type mice initially learnt, but with prolonged training came to withhold responding during the trace-conditioned cue, responding less than for another cue that was nonreinforced. Gria1 knockout mice, in contrast, showed sustained performance over training, responding more to the trace-conditioned cue than the nonreinforced cue. Therefore, the trace-conditioned cue acquired inhibitory properties (signalling the absence of food) in wild-type mice, but Gria1 deletion impaired the acquisition of inhibition, thus maintaining the stimulus as an excitatory predictor of food. Furthermore, when there was no trace both groups showed successful learning. These results suggest that cognitive abnormalities in disorders like schizophrenia in which gluatamatergic signalling is implicated may be caused by aberrant salience leading to a change in the nature of the information that is encoded.
Fabrication-constrained nanophotonic inverse design
Authors: Piggott Alexander Y. , Petykiewicz Jan , Su Logan , Vučković Jelena
Published: May 2017

A major difficulty in applying computational design methods to nanophotonic devices is ensuring that the resulting designs are fabricable. Here, we describe a general inverse design algorithm for nanophotonic devices that directly incorporates fabrication constraints. To demonstrate the capabilities of our method, we designed a spatial-mode demultiplexer, wavelength demultiplexer, and directional coupler. We also designed and experimentally demonstrated a compact, broadband 1 × 3 power splitter on a silicon photonics platform. The splitter has a footprint of only 3.8 × 2.5 μm, and is well within the design rules of a typical silicon photonics process, with a minimum radius of curvature of 100 nm. Averaged over the designed wavelength range of 1400–1700 nm, our splitter has a measured insertion loss of 0.642 ± 0.057 dB and power uniformity of 0.641 ± 0.054 dB.