bluuebunny/crossref_metadata_2025 huggingface dataset:
Investigating Sulfoxide-to-Sulfone Conversion as a Prodrug Strategy for a Phosphatidylinositol 4-Kinase Inhibitor in a Humanized Mouse Model of Malaria
Authors: Gibhard Liezl , Njoroge Mathew , Paquet Tanya , Brunschwig Christel , Taylor Dale , Lawrence Nina , Abay Efrem , Wittlin Sergio , Wiesner Lubbe , Street Leslie J. , Chibale Kelly , Basarab Gregory S.
Published: September 2018

The
in vivo
antimalarial efficacies of two phosphatidylinositol 4-kinase (PI4K) inhibitors, a 3,5-diaryl-2-aminopyrazine sulfoxide and its corresponding sulfone metabolite, were evaluated in the NOD-scid IL2Rγ
null
(NSG) murine malaria disease model of
Plasmodium falciparum
infection. We hypothesized that the sulfoxide would serve as a more soluble prodrug for the sulfone, which would lead to improved drug exposure with oral dosing.
Effects of Phage Endolysin SAL200 Combined with Antibiotics on Staphylococcus aureus Infection
Authors: Kim Nak-Hyun , Park Wan Beom , Cho Jeong Eun , Choi Yoon Jeong , Choi Su Jin , Jun Soo Youn , Kang Chang Kyung , Song Kyoung-Ho , Choe Pyoeng Gyun , Bang Ji-Hwan , Kim Eu Suk , Park Sang Won , Kim Nam-Joong , Oh Myoung-don , Kim Hong Bin
Published: September 2018

Phages and their derivatives are increasingly being reconsidered for use in the treatment of bacterial infections due to the rising rates of antibiotic resistance. We assessed the antistaphylococcal effect of the endolysin SAL200 in combination with standard-of-care (SOC) antibiotics.
Methanogens and Iron-Reducing Bacteria: the Overlooked Members of Mercury-Methylating Microbial Communities in Boreal Lakes
Authors: Bravo Andrea G. , Peura Sari , Buck Moritz , Ahmed Omneya , Mateos-Rivera Alejandro , Herrero Ortega Sonia , Schaefer Jeffra K. , Bouchet Sylvain , Tolu Julie , Björn Erik , Bertilsson Stefan
Published: September 2018

Despite the global awareness that mercury, and methylmercury in particular, is a neurotoxin to which millions of people continue to be exposed, there are sizable gaps in the understanding of the processes and organisms involved in methylmercury formation in aquatic ecosystems. In the present study, we shed light on the diversity of the microorganisms responsible for methylmercury formation in boreal lake sediments. All the microorganisms identified are associated with the processing of organic matter in aquatic systems. Moreover, our results show that the well-known mercury-methylating sulfate-reducing bacteria constituted only a minor portion of the potential mercury methylators. In contrast, methanogens and iron-reducing bacteria were important contributors to methylmercury formation, highlighting their role in mercury cycling in the environment.
Glucose Metabolism by Escherichia coli Inhibits Vibrio cholerae Intestinal Colonization of Zebrafish
Authors: Nag Dhrubajyoti , Breen Paul , Raychaudhuri Saumya , Withey Jeffrey H.
Published: September 2018

The

Vibrio cholerae

O1 serogroup is responsible for pandemic cholera and is divided into the classical and El Tor biotypes. Classical
V. cholerae
produces acid when using glucose as a carbon source, whereas El Tor
V. cholerae
produces the neutral product acetoin when using glucose as a carbon source.
Changes in intraocular pressure after intravitreal fluocinolone acetonide (ILUVIEN): real-world experience in three European countries
Authors: Chakravarthy Usha , Taylor Simon R , Koch Frank H Johannes , Castro de Sousa João Paulo , Bailey Clare
Published: September 2018

Aims

The ILUVIEN Registry Safety Study is an ongoing, multicentre, open-label, observational study collecting real-world data on the safety and effectiveness of the 0.2 µg/day fluocinolone acetonide (FAc) implant in patients treated according to the European label requirements.

Methods

Patients included in this analysis were treated for the licensed indication of chronic diabetic macular oedema (cDMO; that is, DMO that persists or recurs despite treatment). Data presented in the current analysis were collected from patient records up to 6 March 2017. Visual acuity (VA) data, including mean change in VA over time and at last observation, intraocular pressure (IOP) over the course of the study, IOP events, use of IOP-lowering therapy and cup:disc ratio were analysed. Information on additional DMO treatments post-FAc implant was also captured.

Results

Five hundred and sixty-three patients (593 eyes) were enrolled on the study. Mean IOP for the overall population remained within the normal range throughout follow-up and 76.7% of patients did not require IOP-lowering therapy following treatment with the FAc implant. Sixty-nine per cent of eyes did not require additional DMO treatments. Mean VA in the overall population increased from 51.9 letters at baseline to 55.6 letters at month 12, with a significant increase of 2.9 letters at last observation. Patients with short-term cDMO experienced greater VA gains than those with long-term cDMO.

Conclusions

The results of this analysis are comparable with those of other studies, including the Fluocinolone Acetate for Macular Edema study. The study reinforces the good safety and effectiveness profile of FAc, and demonstrates the benefit of early FAc treatment.
What do adolescents want from their ED? An evaluation on the preferences and opinions of adolescents attending local EDs
Authors: Bryans Anna , Camilleri-Brennan Julian , Hua Lei , Patel Nandesh , Price Rebecca , Browning Jen
Published: September 2018

Introduction

The adolescent population comprises a significant proportion of attendances to the ED. Despite adolescent patients reporting lower levels of healthcare satisfaction compared with other age groups, their opinions are under-represented in existing literature. This prospective study investigated adolescents’ expectations and preferences regarding the ED service.

Methods

A questionnaire designed by the investigators was distributed to children aged 12–16 years over a 6-month period in 2015 at two EDs in the UK. The questionnaire explored themes such as same-sex and similar-age areas, staff communication and environment. Interviews based on the questionnaire template were also conducted and guardians were permitted to accompany the participant. Verbal informed consent was obtained from both the young person and their guardian to participate in the study.

Results

There were 254 respondents, which represented 8.8% of adolescent attendances in the study period. ‘Cleanliness’ was rated the most important factor within the ED setting with 94.8% of respondents selecting 4 or 5 on a 5-point Likert scale. This was followed by ‘feeling comfortable’, ‘clear explanation’ and ‘staff communication’ (91.2%, 90.8% and 90.4% rating these 4 or 5, respectively). However, when participants were asked to select a single most important factor, being ‘seen quickly’ was selected most frequently (95/206, 46.1%). ‘Entertainment’ was regarded the least important with only 17.0% selecting 4 or 5 on the Likert scale. Preference for being treated in an adult ED compared with a child ED increased with age.

Conclusions

Being ‘seen quickly’ was considered the single most important factor by adolescent patients in the ED. Notably, ‘cleanliness’ and aspects of communication also rated highly, with ‘entertainment’ regarded as least important. The additional insight into the healthcare preferences of the adolescent population provides a platform on which the future ED services can be tailored to the needs of young people.
Endoscopic day case antireflux radiofrequency (Stretta) therapy improves quality of life and reduce proton pump inhibitor (PPI) dependency in patients with gastro-oesophageal reflux disease: a prospective study from a UK tertiary centre
Authors: Viswanath YKS , Maguire Nicola , Obuobi Reece-Bolton , Dhar Anjan , Punnoose Siby
Published: September 2018

Background

Endoscopic antireflux radiofrequency treatment (Stretta) offers a therapeutic alternative for patients suffering from refractory gastro-oesophageal reflux disease (GORD). Current evidence suggests that the treatment may improve symptoms of GORD and decrease requirement for proton pump inhibitor (PPI) therapy.

Methods

Prospective assessment of patients undergoing Stretta, between October 2014 and February 2016, in a UK tertiary referral centre was carried. All patients were assessed for suitability using endoscopy, contrast studies, and pH and manometry studies. The Gastro-oesophageal Reflux Disease-Health-Related Quality of Life (GERD-HRQL) was used to evaluate symptoms along with PPI dependency, pre-Stretta and post-Stretta treatment. Patients were followed up by outpatient clinic appointment and telephone consultation.

Results

Fifty consecutive patients were followed up for a median of 771 days (range 499–1162) following treatment with Stretta. The average GERD-HRQL score improved from 46.2/75 (±14.2) preprocedure to 15.2/75 (±17.3) postprocedure. Dissatisfaction with GORD as measured in the GERD-HRQL decreased from 100% to 10% with three patients showing no improvement (non-responders) at follow up and two late failures at the time of this review. There were no complications and all cases were carried out as day cases.

Conclusion

There are currently few effective therapeutic alternatives to antireflux surgery for refractory GORD. This series corroborates the value and safety of Stretta as a viable option for selected patients who are unwilling or unable to undergo an operation. Stretta improves quality of life and decreases PPI dependency in selected patients with GORD.
Leveraging the power of new molecular technologies in the clinical setting requires unprecedented awareness of limitations and drawbacks: experience of one diagnostic laboratory
Authors: Nfonsam Landry , Ordorica Shelley , Ghani Mahdi , Potter Ryan , Schaffer Audrey , Daoud Hussein , Vasli Nasim , Chisholm Caitlin , Sinclair-Bourque Elizabeth , McGowan-Jordan Jean , Smith Amanda C , Jarinova Olga , Bronicki Lucas
Published: September 2018

Background

Advances in molecular technologies and in-silico variant prediction tools offer wide-ranging opportunities in diagnostic settings, yet they also present with significant limitations.

Objective

Here, we contextualise the limitations of next-generation sequencing (NGS), multiplex ligation-dependent probe amplification (MLPA) and in-silico prediction tools routinely used by diagnostic laboratories by reviewing specific experiences from our diagnostic laboratory.

Methods

We investigated discordant annotations and/or incorrect variant ‘callings’ in exons of 56 genes constituting our cardiomyopathy and connective tissue disorder NGS panels. Discordant variants and segmental duplications (SD) were queried using the National Center for Biotechnology Information (NCBI) Basic Local Alignment Search Tool and the University of California Santa Cruz genome browser, respectively, to identify regions of high homology. Discrepant variant analyses by in-silico models were re-evaluated using updated file entries.

Results

We observed a 5% error rate inMYH7variant ‘calling’ using MLPA, which resulted from >90% homology of theMYH7probe-binding site toMYH6. SDs were detected inTTN,PKP2andMYLK. SDs inMYLKpresented the highest risk (15.7%) of incorrect variant ‘calling’. The inaccurate ‘callings’ and discrepant in-silico predictions were resolved following detailed investigation into the source of error.

Conclusion

Recognising the limitations described here may help avoid incorrect diagnoses and leverage the power of new molecular technologies in diagnostic settings.
Instance-Based Representation Using Multiple Kernel Learning for Predicting Conversion to Alzheimer Disease
Authors: Collazos-Huertas D. , Cárdenas-Peña D. , Castellanos-Dominguez G.
Published: September 2018

The early detection of Alzheimer’s disease and quantification of its progression poses multiple difficulties for machine learning algorithms. Two of the most relevant issues are related to missing data and results interpretability. To deal with both issues, we introduce a methodology to predict conversion of mild cognitive impairment patients to Alzheimer’s from structural brain MRI volumes. First, we use morphological measures of each brain structure to build an instance-based feature mapping that copes with missed follow-up visits. Then, the extracted multiple feature mappings are combined into a single representation through the convex combination of reproducing kernels. The weighting parameters per structure are tuned based on the maximization of the centered-kernel alignment criterion. We evaluate the proposed methodology on a couple of well-known classification machines employing the ADNI database devoted to assessing the combined prognostic value of several AD biomarkers. The obtained experimental results show that our proposed method of Instance-based representation using multiple kernel learning enables detecting mild cognitive impairment as well as predicting conversion to Alzheimers disease within three years from the initial screening. Besides, the brain structures with larger combination weights are directly related to memory and cognitive functions.
FCNC decays of the Higgs bosons in the BGL model
Authors: Bednyakov Alexander , Rutberg Veronika
Published: September 2018

We consider flavor-changing decays of neutral Higgs bosons in the context of CP-conserving BGL model — a variant of 2HDM Type 3 model suggested by Branco, Grimus and Lavoura — in which tree-level FCNC couplings are suppressed by elements of known fermion mixing matrices. The relevant regions of parameter space compatible with experimental restrictions on the SM Higgs properties are studied. We also include current bounds on [Formula: see text] into consideration. In addition, different FCNC decay modes are analyzed for heavier Higgs states [Formula: see text] and conservative estimates for [Formula: see text] are provided. We updated previous studies and found that it cannot be more than 30% for heavy Higgses with masses around 350 GeV.
Anomalous magnetic moment and vortex structure of the electron
Authors: Tiwari S. C.
Published: September 2018

The electron magnetic moment decomposition calculated in QED is proposed to have origin in a multi-vortex internal structure of the electron. This proposition is founded on two important contributions of this work. First, a critical review on Weyl model of electron, Einstein–Rosen bridge and Wheeler’s wormholes leads to a new idea of a topological defect in cylindrical spacetime geometry as a natural representation of the electron. A concrete realization of this idea in terms of the derivation of a new vortex-metric, and its physical interpretation to establish the geometric origin of the electron magnetic moment decomposition constitute the second contribution. Remarkable occurrence of a vortex structure in the basis mode function used in BLFQ is also pointed out indicating wider ramification of the proposed electron model.
The point defect and eigenfield distribution for two-dimensional function photonic crystal
Authors: Liu Ji-Ping , Li Hai-Bo , Meng Xiang-Dong , Zhang Xiao-Ru , Liu Han , Zhang Si-Qi , Liu Xiao-Jing , Li Hong , Ma Ji , Liang Yu , Wu Xiang-Yao
Published: September 2018

With the plane wave expansion method, we introduced the concept and theory of two-dimensional function photonic crystal, and compared the theoretical difference of two-dimensional function photonic crystal with the conventional photonic crystal. In Numerical calculation, with COMSOL software based on finite element method, we have studied the bandgap structure, defect mode and eigenfield distribution for the two-dimensional function photonic crystal with and without point defect. For the two-dimensional function photonic crystal, the dielectric constant of dielectric column is the space coordinate function, which can be realized by the electro-optic effect and the Kerr effect. In the paper, we studied the dielectric constant function form is [Formula: see text](r) = kr + b, and the parameters k and b can be adjusted by changing the electric field or light intensity applied to the dielectric column. By changing the parameters k or b of the dielectric column dielectric constant, we found the two-dimensional function photonic crystal transmission characteristics have the adjustability, i.e., the bandgap structure, the bandgap position and width, the defect mode position, width and number and the defect mode eigenfield distribution can be changed by adjusting the parameters k or b, which can be used to conveniently design the bandgap structure that we need. These conclusions will provide important theoretical basis and methods for optical devices design.
An improved label propagation algorithm based on node intimacy for community detection in networks
Authors: Kong Hanzhang , Kang Qinma , Liu Chao , Li Wenquan , He Hong , Kang Yunfan
Published: September 2018

Community detection in complex network analysis is a quite challenging problem spanning many applications in various disciplines such as biology, physics and social network. A large number of methods have been developed for this problem, among which the label propagation algorithm (LPA) has attracted much attention because of its advantages of nearly-linear running time and easy implementation. Nevertheless, the random updating order and tie-breaking strategy in LPA make the algorithm unstable and may even lead to the formation of a monster community. In this paper, an improved LPA called LPA-INTIM is proposed for solving the community detection problem. Firstly, an intimacy matrix is constructed using local topology information for measuring the intimacy between nodes. And then, the node importance is calculated to ensure that nodes are updated in a specific order. Finally, the label influence is evaluated for updating node label during the label propagation process. In addition, we introduce a novel tightness function to improve the stability of the proposed algorithm. By the comparison with the methods presented in the literatures, experimental results on real-world and synthetic networks show the efficiency and effectiveness of our proposed algorithm.
Phase diagrams of the random nearest-neighbor mixed spin-1/2 and spin-3/2 Blume–Capel model
Authors: Albayrak Erhan
Published: September 2018

The mixed spin-1/2 and spin-3/2 Blume–Capel (BC) model is considered on the Bethe lattice (BL) with randomly changing coordination numbers (CN) and examined in terms of exact recursion relations. A couple of two different CNs are changed randomly on the shells of the BL in terms of a standard–random approach to obtain the phase diagrams on possible planes of the system parameters. It is found from the thermal analysis of the order-parameters that the model only gives the second-order phase transitions as in the regular mixed case. As the probability of having larger CN increases, the temperatures of the critical lines also increase as expected.
Dynamics of multi-soliton and breather solutions for a new semi-discrete coupled system related to coupled NLS and coupled complex mKdV equations
Authors: Wang Hao-Tian , Wen Xiao-Yong
Published: September 2018

In this paper, a new semi-discrete coupled system which was firstly proposed by Bronsard and Pelinovsky is under investigation. Based on its known Lax pair, the infinitely-many conservation laws and discrete N-fold DT for this system are constructed. As applications, bell-shaped multi-soliton and breather solutions in terms of determinants for this system are firstly derived by means of the discrete N-fold DT. Propagation and elastic interaction structures of such soliton solutions are shown graphically: (1) Propagation characteristics of one-, two-, three- and four-soliton solutions are discussed from vanishing background. (2) Propagation characteristics of one- and two-breather solutions are analyzed from the plane wave background. The details of the dynamical evolutions for such soliton and breather solutions are studied via numerical simulations. Numerical results show the accuracy of our numerical scheme and the stable evolutions of these solitons with or without a noise in a relatively short period of time, while the evolutions exhibit obviously larger oscillations and strong instability with the increase in time. These results may be useful for understanding the propagation of orthogonally polarized optical waves in an isotropic medium and circularly polarized few-cycle pulses in Kerr media described by the coupled NLS and coupled complex mKdV equations, respectively.
Mixed type exact solutions to the (2+1)-dimensional Ito equation
Authors: Liu Jian-Guo , Ai Guo-Ping , Zhu Wen-Hui
Published: September 2018

Using a direct test function based on the Hirota’s bilinear form, two classes of mixed type exact solutions to the (2[Formula: see text]+[Formula: see text]1)-dimensional Ito equation are found through symbolic computations with Mathematica. These mixed type exact solutions contain exponential function, trigonometric function and hyperbolic function. The physical structures and characteristics for these resulting mixed type exact solutions are illustrated by some three-dimensional plots and contour plots.
Stability analysis, soliton waves, rogue waves and interaction phenomena for the (3+1)-dimensional generalized Kadomtsev–Petviashvili equation
Authors: Guo Ding , Tian Shou-Fu
Published: September 2018

In this paper, the (3[Formula: see text]+[Formula: see text]1)-dimensional generalized Kadomtsev–Petviashvili (gKP) equation is discussed, which can be used to describe certain characteristics of soliton in a nonlinear media with weak dispersion. By using the virtue of Bell polynomial, we construct the exact bilinear formalism and soliton wave of the equation, respectively. We also analyze its stability analysis. Moreover, based on the resulting bilinear formalism, we obtain its rouge wave solutions with a direct method. Finally, we also discuss the interaction phenomena between solitary wave solutions and rogue wave solutions. It is hoped that our results can be used to enrich the dynamics of the (3[Formula: see text]+[Formula: see text]1)-dimensional nonlinear wave fields.
Friedmann’s equation and the creation of the universe
Authors: Fischer Arthur E.
Published: September 2018

In this paper, we present mathematical evidence that the beginning of the universe did not occur at the big bang at [Formula: see text] with the universe in a state of infinite density, but occurred at [Formula: see text] with the universe in a state of infinite dilution. We show the essential importance played by the native quadratic structure of a generic Friedmann’s equation [Formula: see text] in the time derivative [Formula: see text] in arriving at this conclusion and show how this quadratic structure together with the accompanying time-reversal symmetry of Friedmann’s equation has profound physical consequences in building Friedmann models of the universe, one of which is that classical cosmological models can be extrapolated backward through the big bang into the infinite past. We conclude that viable cosmological models based on the native quadratic form of Friedmann’s equation, and thus on Einstein’s equations, show that global spatial singularities need not signal an end to spacetime. Moreover, classical big bang cosmological models based on Friedmann’s equation, without the need for quantum gravity, when globalized to all-time solutions, show that the universe did not begin at the big bang. Thus encoded in Friedmann’s equation is previously undiscovered information about how the universe began and we show that this information can only be extracted when Friedmann’s equation is taken in its native quadratic form as opposed to the usual approach of considering only the positive square root form of Friedmann’s equation.
Ratio of the jet power to the bolometric luminosity of the disk during accretion onto a black hole
Authors: Bogovalov S. V.
Published: September 2018

Disk accretion onto black holes is accompanied by collimated outflows (jets). In active galactic nuclei (AGN), the kinetic energy flux of the jet (jet power or kinetic luminosity) may exceed the bolometric luminosity of the disk by a few orders of magnitude. This may be explained in the framework of the so-called “cold” disk accretion when the only source of the AGN energy is the energy released by accretion. The radiation from the disk is suppressed because the disk wind carries out almost all the angular momentum and the gravitational energy of the accreting material. In this paper, we calculate the “unavoidable” radiation from the “cold” disk and the ratio of the kinetic energy power of the outflow to the bolometric luminosity of the accretion disk around a super massive black hole in the framework of the Shakura and Sunyaev paradigm of an optically thick [Formula: see text]-disk. The exploration of the Fundamental Plane of Black Holes allows us to obtain equations that define the bolometric luminosity and the ratio of the luminosities as functions of the black hole mass and accretion rate. The application of our equations in the case of the M87 jet demonstrates good agreement with observations. In the case of Sgr A*, these equations allow us to predict the kinetic energy flux from the disk around the Galactic supermassive black hole.
A COMPARATIVE STUDY ON VACUUM AND ATMOSPHERIC PLASMA SPRAYED TANTALUM COATINGS FOR THE MODIFICATION OF TITANIUM IMPLANTS
Authors: DING DING , XIE YOUTAO , LI KAI , HUANG LIPING , ZHENG XUEBIN
Published: September 2018

In order to improve the mechanical compatibility and cytocompatibility of titanium implants, tantalum coatings were prepared using plasma spraying technology. Tantalum coatings have been deposited via atmospheric plasama spraying (APS) and vacuum plasma spraying (VPS) methods, and then their morphologies, porosities, bonding strengths and elastic modulous were investigated. In vitro cytocompatibility of the two coatings was evaluated via human bone marrow stromal cells (hBMSCs). The results show that oxidation phenomenon was observed for the APS tantalum coatings, while less oxidation was found in the VPS tantalum coatings. Compared with APS tantalum coatings, the VPS tantalum coatings have a more compact microstructure and less impurity content, resulting in a better bonding with the titanium substrate. VPS tantalum coatings were measured to have a lower elastic modulus and a higher hardness than APS Tantalum coatings. Electrochemical corrosion of the coatings were examined and the VPS tantalum coating showed improved chemical stability. Besides, bone marrow stem cells (BMSCs) adhere to and spread well on the surface of both VPS and APS tantalum coatings without significant difference. The proliferation rate of BMSCs is higher on VPS tantalum coating surface than on APS tantalum coatings. Our results suggest that VPS tantalum coatings are more suitable for the application of surface modification of titanium implant due to their lower elastic modulus and better chemical stability for higher mechanical compatibility and cytocompatibility.
CROSS-LINKS MULTISCALE EFFECTS ON BONE ULTRASTRUCTURE BIOMECHANICAL BEHAVIOR
Authors: KRAIEM TESNIM , BARKAOUI ABDELWAHED , MERZOUKI TAREK , CHAFRA MOEZ
Published: September 2018

Bone is a multiscale combination of collagen molecules merged with mineral crystals. Its high rigidity and stability stem amply from its polymeric organic matrix and secondly from the connections established between interdifferent and intradifferent scale components through cross-links. Several studies have shown that the cross-links inhibition results in a reduction in strength of bone but they do not quantify the degree to which these connections contribute to the bone rigidity and toughness. This report is classified among the few works that measure the cross-links multiscale impact on the ultrastructure bone mechanical behavior.

This work aims firstly to study the effect of cross-links at the molecule scale and secondly to gather from literature studies results handling with cross-links effects on the other bone ultrastructure scales in order to reveal the multiscale effect of cross-links. This study proves that cross-links increasing number improves the mechanical performance of each scale of bone ultrastructure. On the other hand, cross-links have a multiscale contribution that depends on its rank related to existing cross-links connecting the same geometries and it depends on mechanical characteristics of geometries connected.
Detection of Control Structures in Spoken Utterances
Authors: Weigelt Sebastian , Hey Tobias , Steurer Vanessa
Published: September 2018

State-of-the-art intelligent assistant systems such as Siri and Cortana do not consider control structures in the user input. They reliably react to ordinary commands. However, their architectures are not designed to cope with queries that require complex control flow structuring. We propose a system to overcome these limitations. Our approach models if-then-else, loop, and concurrency constructs in spoken utterances explicitly. The model bridges the gap between linguistic and programmatic semantics.

To demonstrate our concept, we apply a rule-based approach. We have implemented three prototypes that use keyphrases to discover potential control structures depending on the type of control structure. However, the full structures are determined differently. For conditionals we use chunk and part-of-speech (POS) tags provided by natural language processing tools; for loops and concurrency we make use of an action extraction approach based on semantic role labeling (SRL). Additionally, we use coreference information to determine the extent of the respective structure.

The explicit modeling of conditionals, loops, and concurrent sections allows us to evaluate the accuracy of our approaches independently from each other and from other language understanding tasks. We have conducted two user studies in the domain of humanoid robotics. The first focused on conditionals. Our prototype achieves F1scores from 0.783 (automatic speech recognition) to 0.898 (manual transcripts) on unrestricted utterances. In the second, the prototypes for loop and concurrency detection also proved useful. F1scores range from 0.588 (automatic speech recognition) to 0.814 (manual transcripts) for loops and from 0.622 (automatic speech recognition) to 0.842 (manual transcripts) for concurrent sections respectively.
Morita’s trace maps on the group of homology cobordisms
Authors: Massuyeau Gwénaël , Sakasai Takuya
Published: September 2018

Morita introduced in 2008 a [Formula: see text]-cocycle on the group of homology cobordisms of surfaces with values in an infinite-dimensional vector space. His [Formula: see text]-cocycle contains all the “traces” of Johnson homomorphisms which he introduced 15 years earlier in his study of the mapping class group. In this paper, we propose a new version of Morita’s [Formula: see text]-cocycle based on a simple and explicit construction. Our [Formula: see text]-cocycle is proved to satisfy several fundamental properties, including a connection with the Magnus representation and the LMO homomorphism. As an application, we show that the rational abelianization of the group of homology cobordisms is non-trivial. Besides, we apply some of our algebraic methods to compare two natural filtrations on the automorphism group of a finitely-generated free group.
Safety concept, FEP catalogue and scenario development as fundamentals of a long-term safety demonstration for high-level waste repositories in German clay formations
Authors: Lommerzheim A. , Jobmann M. , Meleshyn A. , Mrugalla S. , Rübel A. , Stark L.
Published: September 2018

A safety concept and a safety demonstration concept for the disposal of high-level radioactive waste in German clay formations have been developed. The main safety objective is to retain the radionuclides inside a ‘Containment Providing Rock Zone’. Thus, the radionuclide transport should be restrained by adequate safety functions of the geological and geotechnical barriers. The compliance with legal dose constraints has to be demonstrated for probable evolutions and less probable evolutions.

As a basis for system analysis, generic geological reference models, disposal concepts and repository designs have been developed for northern and southern Germany. All data relevant for future system evolution were compiled in two FEP (features, events and processes) catalogues. They provide information on FEP characteristics, their probabilities of occurrence, their interactions and identify ‘initial FEP’ that impair the safety functions of relevant barriers. A probable reference scenario has been deduced systematically from the probable ‘initial FEP’, and from probable processes relevant for radionuclide mobilization and transport. Four different starting points to develop alternative scenarios (i.e. less probable evolutions) were identified.

The scenario development methodology is applicable to different kinds of host rock and therefore may be a basis for the preliminary safety analyses necessary in the future site selection process in Germany.
Computational model-based assessment of baroreflex function from response to Valsalva maneuver
Authors: Kosinski Samuel A. , Carlson Brian E. , Hummel Scott L. , Brook Robert D. , Beard Daniel A.
Published: September 2018

Functional metrics of autonomic control of heart rate, including baroreflex sensitivity, have been shown to be strongly associated with cardiovascular risk. A decrease in baroreflex sensitivity with aging is hypothesized to represent a contributing causal factor in the etiology of primary hypertension. To assess baroreflex function in human subjects, two complementary methods to simulate the response in heart rate elicited by the Valsalva maneuver were developed and applied to data obtained from a cohort of healthy normal volunteers. The first method is based on representing the baroreflex arc as a simple linear filter, transforming changes in arterial pressure to changes in R-R interval. The second method invokes a physiologically based model for arterial mechanics, afferent baroreceptor strain-dependent firing, and control of heart rate via central autonomic response to changes in afferent inputs from aortic and carotid sensors. Analysis based on the linear filter model reveals that the effective response time of the baroreflex arc tends to increase with age in healthy subjects and that the response time/response rate is a predictor of resting systolic pressure. Similar trends were obtained based on the physiologically based model. Analysis of the Valsalva response using the physiologically based model further reveals that different afferent inputs from the carotid sinus and the aortic arch baroreceptors govern different parts of the heart rate response. The observed relationship between baroreflex sensitivity and systolic pressure is surprising because hypertensive subjects were excluded from the study, and there was no observed relationship between arterial pressure and age.

NEW & NOTEWORTHY We introduce two methods to assess baroreflex function from data recorded from human subjects performing the Valsalva maneuver. Results demonstrate that the baroreflex response time tends to increase with age in healthy subjects, that response time represents a predictor of resting systolic pressure, and that the Valsalva response reveals different effects mediated by baroreceptors in the carotid sinus compared with those in the aortic arch.
Diaphragm muscle function following midcervical contusion injury in rats
Authors: Khurram Obaid U. , Fogarty Matthew J. , Rana Sabhya , Vang Pangdra , Sieck Gary C. , Mantilla Carlos B.
Published: September 2018

Midcervical spinal cord contusion injury results in tissue damage, disruption of spinal pathways, and motor neuron loss. Unilateral C4 contusion results in loss of 40%–50% of phrenic motor neurons ipsilateral to the injury (~25% of the total phrenic motor neuron pool). Over time after unilateral C4 contusion injury, diaphragm muscle (DIAm) electromyogram activity increases both contralateral and ipsilateral to the side of injury in rats, suggesting compensation because of increased activation of the surviving motor neurons. However, the impact of contusion injury on DIAm force generation is less clear. Transdiaphragmatic pressure (Pdi) was measured across motor behaviors over time after unilateral C4 contusion injury in adult male Sprague-Dawley rats. Maximum Pdi (Pdimax) was elicited by bilateral phrenic nerve stimulation at 7 days postinjury. We hypothesized that Pdimaxis reduced following unilateral C4 contusion injury, whereas ventilatory behaviors of the DIAm are unimpaired. In support of our hypothesis, Pdimaxwas reduced by ~25% after unilateral C4 contusion, consistent with the extent of phrenic motor neuron loss following contusion injury. One day after contusion injury, the Pdi amplitude during airway occlusion was reduced from ~30 to ~20 cmH2O, but this reduction was completely reversed by 7 days postinjury. Ventilatory behaviors (~10 cmH2O), DIAm-specific force, and muscle fiber cross-sectional area did not differ between the laminectomy and contusion groups. These results indicate that the large reserve capacity for DIAm force generation allows for higher-force motor behaviors to be accomplished despite motor neuron loss, likely reflecting changes in motor unit recruitment.

NEW & NOTEWORTHY Respiratory muscles such as the diaphragm generate the pressures necessary to accomplish a variety of motor behaviors ranging from ventilation to near-maximal expulsive behaviors. However, the impact of contusion injury on diaphragm pressure generation across behaviors is not clear. The present study shows that contusion injury impairs maximal pressure generation while preserving the ability of the diaphragm to accomplish lower-force motor behaviors, likely reflecting changes in diaphragm motor unit recruitment.
Identification of differentially expressed genes in broiler offspring under maternal folate deficiency
Authors: Xing Jinyi , Jing Wenqian , Zhang Yujie , Liu Lin , Xu Junjie , Chen Xianwei
Published: September 2018

Folate plays an important role in DNA and RNA synthesis by donating methyl groups. To investigate the effects of maternal folate deficiency (FD) on the abdominal adipose transcriptome and on the accumulation of lipid droplets in the liver tissue of chicken offspring, differentially expressed genes (DEGs) of FD were identified with digital gene expression tag profiling. Ultramicroscopy suggested that the size of lipid droplets in hepatocytes increased with FD, while the lipid droplets population number was largely not affected. The serum parameters assay showed that the concentrations of MTHFR (476.57 vs. 395.27), DHFR (45.056 vs. 38.952), LPL (50.408 vs. 48.677), HCY (4.354 vs. 3.836), LEP (9.951 vs. 8.673), and IGF2 (1209.4 vs. 1027.7) in offspring serum of the FD group were significantly higher than those of the normal folate (NF) group ( P < 0.01). The 442 DEGs between NF and FD groups were identified by digital gene expression profiling. Considering the DEGs in the FD groups vs. NF groups, 179 genes were upregulated while 263 downregulated, and in particular, 145 upregulated and 214 downregulated DEGs were successfully annotated with the nonredundant database. Gene Ontology analysis showed that FD mainly affected cellular processes, cell part and binding, cell killing, virions, and receptor regulator activity. With pathway analysis, it indicated that 123 unigenes were assigned to 115 KEGG pathways, but only five of 115 these pathways were significantly enriched with P values ≤ 0.05. Taken together, these results provide a foundation for further studying the responses of offspring to maternal FD in breeding chickens.
NK Cell Education in Tumor Immune Surveillance: DNAM-1/KIR Receptor Ratios as Predictive Biomarkers for Solid Tumor Outcome
Authors: Guillamón Concepción F. , Martínez-Sánchez María V. , Gimeno Lourdes , Mrowiec Anna , Martínez-García Jerónimo , Server-Pastor Gerardo , Martínez-Escribano Jorge , Torroba Amparo , Ferri Belén , Abellán Daniel , Campillo José A. , Legaz Isabel , López-Álvarez María R. , Moya-Quiles María Rosa , Muro Manuel , Minguela Alfredo
Published: September 2018

Natural killer cell (NKc)-based therapies offer promising outcomes in patients with tumors, but they could improve with appropriate selection of donors and optimization of methods to expand NKcs in vitro. Education through licensing interactions of inhibitory killer cell immunoglobulin-like receptors (iKIR) and NKG2A with their cognate HLA class-I ligands optimizes NKc functional competence. This work has evaluated the role of licensing interactions in NKc differentiation and the survival of cancer patients. We have analyzed KIR and KIR-ligand genes, and the expression of activating (CD16 and DNAM-1/CD226) and inhibitory (NKG2A and iKIRs) receptors on peripheral blood NKcs in 621 healthy controls and 249 solid cancer patients (80 melanoma, 80 bladder, and 89 ovarian). Licensing interactions upregulated the expression of activating CD226, reduced that of iKIR receptors, and shifted the CD226/iKIR receptor ratio on NKc membranes to activating receptors. A high tumor burden decreased CD226 expression, reduced the ratio of CD226/iKIR, and negatively affected patient survival. The progression-free survival (38.1 vs. 67.0 months, P < 0.002) and overall survival (56.3 vs. 99.6 months, P < 0.00001) were significantly shorter in patients with lower expression of CD226 on NKcs. Hence, transformed cells can downmodulate these licensing-driven receptor rearrangements as a specific mechanism to escape NKc immune surveillance. Our results suggest the importance of the CD226/iKIR receptor ratio of NKcs induced by licensing interactions as critical determinants for solid cancer immune surveillance, and may provide predictive biomarkers for patient survival that may also improve the selection of donors for NKc immunotherapy.
Cell Sheet-Based Vascularized Myocardial Tissue Fabrication
Authors: Komae Hyoe , Ono Minoru , Shimizu Tatsuya
Published: September 2018

Background: The development of regenerative medicine in recent years has been remarkable as tissue engineering technology and stem cell research have advanced. The ultimate goal of regenerative medicine is to fabricate human organs artificially. If fabricated organs can be transplanted medically, it will be the innovative treatment of diseases for which only donor organ transplantation is the definitive therapeutic method at present. Summary: Our group has reported successful fabrication of thick functional myocardial tissue in vivo and in vitro by using cell sheet engineering technology which requires no scaffolds. Thick myocardial tissue can be fabricated by stacking cardiomyocyte sheets on the vascular bed every 24 h, so that a vascular network can be formed within the myocardial graft. We call this procedure a multi-step transplantation procedure. After human-induced pluripotent stem cells were discovered and human cardiomyocytes became available, a thick, macroscopically pulsate human myocardial tissue was successfully constructed by using a multi-step transplantation procedure. Furthermore, our group succeeded in fabricating functional human myocardial tissue which can generate pressure. Here, we present our way of fabricating human myocardial tissue by means of cell sheet engineering technology. Key Messages: Our group succeeded in fabricating thick, functional human myocardium which can generate pulse pressure. However, there are still a few problems to be solved until clinically functional human cardiac tissue or a whole heart can be fabricated. Research on myocardial regeneration progresses at such a pace that we believe the products of this research will save many lives in the near future.
The Arteriovenous Loop: Engineering of Axially Vascularized Tissue
Authors: Weigand Annika , Horch Raymund E. , Boos Anja M. , Beier Justus P. , Arkudas Andreas
Published: September 2018

Background: Most of the current treatment options for large-scale tissue defects represent a serious burden for the patients, are often not satisfying, and can be associated with significant side effects. Although major achievements have already been made in the field of tissue engineering, the clinical translation in case of extensive tissue defects is only in its early stages. The main challenge and reason for the failure of most tissue engineering approaches is the missing vascularization within large-scale transplants. Summary: The arteriovenous (AV) loop model is an in vivo tissue engineering strategy for generating axially vascularized tissues using the own body as a bioreactor. A superficial artery and vein are anastomosed to create an AV loop. This AV loop is placed into an implantation chamber for prevascularization of the chamber inside, e.g., a scaffold, cells, and growth factors. Subsequently, the generated tissue can be transplanted with its vascular axis into the defect site and anastomosed to the local vasculature. Since the blood supply of the growing tissue is based on the AV loop, it will be immediately perfused with blood in the recipient site leading to optimal healing conditions even in the case of poorly vascularized defects. Using this tissue engineering approach, a multitude of different axially vascularized tissues could be generated, such as bone, skeletal or heart muscle, or lymphatic tissues. Upscaling from the small animal AV loop model into a preclinical large animal model could pave the way for the first successful attempt in clinical application. Key Messages: The AV loop model is a powerful tool for the generation of different axially vascularized replacement tissues. Due to minimal donor site morbidity and the possibility to generate patient-specific tissues variable in type and size, this in vivo tissue engineering approach can be considered as a promising alternative therapy to current treatment options of large-scale defects.
Glandular Cell Abnormalities on SurePath Preparations: A Retrospective Review with Cytology-Histology Correlations
Authors: Fischer Gabor , Cormier Karen
Published: September 2018

Objective: Detecting glandular lesions is challenging by all Pap test methodologies. As the availability of data on identifying glandular abnormalities by SurePath is scarce, we investigated the detection rates and the correlation with histology follow-up. Study Design: A total of 105,927 cases (SurePath and conventional) were searched for the diagnosis of atypical glandular cells or higher glandular abnormalities (AGC+) with the corresponding histologic diagnosis. The associations between the Pap test methods and diagnostic categories were assessed by χ2 test. Results: Overall, 0.32% of SurePath (159/49,375) and 0.29% of conventional (164/56,552) cases showed AGC+ (p = 0.38). Histology confirmed significant abnormalities in 42 versus 53.5% of the cases, respectively (p = 0.064); 72.7% (SurePath) versus 65.2% (conventional) of these were glandular in nature (p = 0.37). The diagnosis of neoplasia (favored or definitive) showed malignancy on follow-up in 100% of SurePath cases (12/12). In contrast, 82.1% of these conventional cases disclosed premalignant or malignant lesions by histology (p = 0.12). Conclusions: AGC+ cases showed higher prevalence on SurePath preparations. Conventional cases had more abnormalities on follow-up, while glandular lesions represented a higher proportion of abnormal histologies following SurePath AGC+s. The positive predictive value of favored or definite neoplasia was higher in SurePath cases. Overall, these differences were not statistically significant.