bluuebunny/crossref_metadata_2025 huggingface dataset:
A dark mode in scanning thermal microscopy
Authors: Ramiandrisoa Liana , Allard Alexandre , Joumani Youssef , Hay Bruno , Gomés Séverine
Published: December 2017

The need for high lateral spatial resolution in thermal science using Scanning Thermal Microscopy (SThM) has pushed researchers to look for more and more tiny probes. SThM probes have consequently become more and more sensitive to the size effects that occur within the probe, the sample, and their interaction. Reducing the tip furthermore induces very small heat flux exchanged between the probe and the sample. The measurement of this flux, which is exploited to characterize the sample thermal properties, requires then an accurate thermal management of the probe-sample system and to reduce any phenomenon parasitic to this system. Classical experimental methodologies must then be constantly questioned to hope for relevant and interpretable results. In this paper, we demonstrate and estimate the influence of the laser of the optical force detection system used in the common SThM setup that is based on atomic-force microscopy equipment on SThM measurements. We highlight the bias induced by the overheating due to the laser illumination on the measurements performed by thermoresistive probes (palladium probe from Kelvin Nanotechnology). To face this issue, we propose a new experimental procedure based on a metrological approach of the measurement: a SThM “dark mode.” The comparison with the classical procedure using the laser shows that errors between 14% and 37% can be reached on the experimental data exploited to determine the heat flux transferred from the hot probe to the sample.
Evolution of intense laser pulse spot size propagating in collisional plasma embedded in magnetic field with variable direction
Authors: Malekshahi Moslem
Published: December 2017

In this study, propagation of an intense laser pulse through collisional, homogenous, magnetized plasma has been investigated. The plasma is embedded in an external magnetic field with the amplitude and variable direction being constant. The complex dispersion relation of the plasma medium has been obtained that predicates the Faraday rotation effect. The paraxial wave equation has been used for the study of propagation of laser pulse in plasma. The nonlinear current density vector as a source of wave equation is obtained by motion equation and continuity equation of plasma free electrons. Using the source dependent expansion method, the evolution of laser pulse spot size has been investigated. It is shown that the spot size of the laser pulse is dependent on the strength and direction of the external magnetic field significantly. The effect of collision frequency on the evolution of spot size has been studied. The space damping rate of laser pulse power along the propagation length due to collision is obtained. Results show that the increase in the external magnetic field strength increases the rate of laser energy loss.
Magnetically targeted delivery through cartilage
Authors: Jafari Sahar , Mair Lamar O. , Chowdhury Sagar , Nacev Alek , Hilaman Ryan , Stepanov Pavel , Baker-McKee James , Ijanaten Said , Koudelka Christian , English Bradley , Malik Pulkit , Weinberg Irving N.
Published: December 2017

In this study, we have invented a method of delivering drugs deep into articular cartilage with shaped dynamic magnetic fields acting on small metallic magnetic nanoparticles with polyethylene glycol coating and average diameter of 30 nm. It was shown that transport of magnetic nanoparticles through the entire thickness of bovine articular cartilage can be controlled by a combined alternating magnetic field at 100 Hz frequency and static magnetic field of 0.8 tesla (T) generated by 1" dia. x 2" thick permanent magnet. Magnetic nanoparticles transport through bovine articular cartilage samples was investigated at various settings of magnetic field and time durations. Combined application of an alternating magnetic field and the static field gradient resulted in a nearly 50 times increase in magnetic nanoparticles transport in bovine articular cartilage tissue as compared with static field conditions. This method can be applied to locally deliver therapeutic-loaded magnetic nanoparticles deep into articular cartilage to prevent cartilage degeneration and promote cartilage repair in osteoarthritis.
Microwave monolithic filter and phase shifter using magnetic nanostructures
Authors: Aslam Shehreen , Khanna Manoj , Veenugopal Veerakumar , Kuanr Bijoy K.
Published: December 2017

Monolithic Microwave Integrated Circuit (MMIC) have major impact on the development of microwave communication technology. Transition metal based ferromagnetic nano-wired (FMNWs) substrate are of special interest in order to fabricate these MMIC devices. Their saturation magnetization is comparatively higher than ferrites which makes them suitable for high frequency (>10 ∼ 40 GHz) operation at zero or a small applied magnetic field. The CoFeB nanowires in anodic alumina templates were synthesized using three-electrode electro-deposition system. After electro-deposition, 1μm thick Cu layer was sputtered on the top surface of FMNW substrate and lithography was done to design microstrip lines. These microstrip transmission lines were tested for band-stop filters and phase shifters based on ferromagnetic resonance (FMR) over a wide applied magnetic field (H) range. It was observed that attenuation and frequency increase with the increase of magnetic field (upto 5.3 kOe). For phase shifter, the influence of magnetic material was studied for two frequency regions: (i) below FMR and (ii) above FMR. These two frequency regions were suitable for many practical device applications as the insertion loss was very less in these regions in comparison to resonance frequency regions. In the high frequency region (at 35 GHz), the optimal differential phase shift increased significantly to ∼ 250 deg/cm and around low frequency region (at 24 GHz), the optimal differential phase shift is ∼175 deg/cm at the highest field (H) value.
Modeling and analysis of Galfenol cantilever vibration energy harvester with nonlinear magnetic force
Authors: Cao Shuying , Sun Shuaishuai , Zheng Jiaju , Wang Bowen , Wan Lili , Pan Ruzheng , Zhao Ran , Zhang Changgeng
Published: December 2017

Galfenol traditional cantilever energy harvesters (TCEHs) have bigger electrical output only at resonance and exhibit nonlinear mechanical-magnetic-electric coupled (NMMEC) behaviors. To increase low-frequency broadband performances of a TCEH, an improved CEH (ICEH) with magnetic repulsive force is studied. Based on the magnetic dipole model, the nonlinear model of material, the Faraday law and the dynamic principle, a lumped parameter NMMEC model of the devices is established. Comparisons between the calculated and measured results show that the proposed model can provide reasonable data trends of TCEH under acceleration, bias field and different loads. Simulated results show that ICEH exhibits low-frequency resonant, hard spring and bistable behaviors, thus can harvest more low-frequency broadband vibration energy than TCEH, and can elicit snap-through and generate higher voltage even under weak noise. The proposed structure and model are useful for improving performances of the devices.
Investigation of thermal conduction in symmetric and asymmetric nanoporous structures
Authors: Yu Ziqi , Ferrer-Argemi Laia , Lee Jaeho
Published: December 2017

Nanoporous structures with a critical dimension comparable to or smaller than the phonon mean free path have demonstrated significant thermal conductivity reductions that are attractive for thermoelectric applications, but the presence of various geometric parameters complicates the understanding of governing mechanisms. Here, we use a ray tracing technique to investigate phonon boundary scattering phenomena in Si nanoporous structures of varying pore shapes, pore alignments, and pore size distributions, and identify mechanisms that are primarily responsible for thermal conductivity reductions. Our simulation results show that the neck size, or the smallest distance between nearest pores, is the key parameter in understanding nanoporous structures of varying pore shapes and the same porosities. When the neck size and the porosity are both identical, asymmetric pore shapes provide a lower thermal conductivity compared with symmetric pore shapes, due to localized heat fluxes. Asymmetric nanoporous structures show possibilities of realizing thermal rectification even with fully diffuse surface boundaries, in which optimal arrangements of triangular pores show a rectification ratio up to 13 when the injection angles are optimally controlled. For symmetric nanoporous structures, hexagonal-lattice pores achieve larger thermal conductivity reductions than square-lattice pores due to the limited line of sight for phonons. We also show that nanoporous structures of alternating pore size distributions from large to small pores yield a lower thermal conductivity compared with those of uniform pore size distributions in the given porosity. These findings advance the understanding of phonon boundary scattering phenomena in complex geometries and enable optimal designs of artificial nanostructures for thermoelectric energy harvesting and solid-state cooling systems.
Hybrid gap plasmon GaAs nanolasers
Authors: Nguyen Ngoc B. , Nielsen Michael P. , Lafone Lucas , Clarke Edmund , Fry Paul , Oulton Rupert F.
Published: December 2017

Compact semiconductor lasers with sub-wavelength-scale dimensions rely heavily on materials with low surface recombination due to the large surface area to volume ratios of their nano-cavities. Furthermore, the reliance on semiconductor nanostructures has led to predominantly bottom-up fabrication approaches, which has hindered scalable and practical applications. In this letter, we present lithographically constructed hybrid gap plasmon nanolasers using the gain of bulk GaAs operating at room temperature. The nanolasers are built on GaAs suspended membranes with InGaP passivation layers. Laser resonators are defined only by patterning gold on top of these GaAs membranes, thus eliminating the need to etch the semiconductor for optical confinement, which would introduce additional surface recombination. An analysis of the modal gain and losses in these devices suggests that threshold carrier densities in the range of 4–5×1018 cm−3 are necessary—potentially achievable with current densities as low as 6–8 kA cm−2.
On the lifetime of metastable metallic hydrogen
Authors: Burmistrov S. N. , Dubovskii L. B.
Published: December 2017

The molecular phase of hydrogen converts to the atomic metallic phase at high pressures estimated usually as 300–500 GPa. We analyze the zero-temperature decay of metallic phase as the pressure is relieved below the transition one. The metallic state is expected to be in the metastable long-lived state down to about 10–20 GPa and decays instantly at the lower pressures. The pressure range of the long-lived metastable state is directly associated with an impossibility to produce a stable hydrogen molecule immersed into the electron liquid of high density. For lower pressures, the nucleation of an electron-free cavity with the energetically favorable hydrogen molecule inside cannot be suppressed with the low ambient pressure.
Surface-induced effects in fluctuation-based measurements of single-polymer elasticity: A direct probe of the radius of gyration
Authors: Innes-Gold Sarah N. , Morgan Ian L. , Saleh Omar A.
Published: December 2017

Single-molecule measurements of polymer elasticity are powerful, direct probes of both biomolecular structure and principles of polymer physics. Recent work has revealed low-force regimes in which biopolymer elasticity is understood through blob-based scaling models. However, the small tensions required to observe these regimes have the potential to create measurement biases, particularly due to the increased interactions of the polymer chain with tethering surfaces. Here, we examine one experimentally observed bias, in which fluctuation-based estimates of elasticity report an unexpectedly low chain compliance. We show that the effect is in good agreement with predictions based on quantifying the exclusion effect of the surface through an image-method calculation of available polymer configurations. The analysis indicates that the effect occurs at an external tension inversely proportional to the polymer’s zero-tension radius of gyration. We exploit this to demonstrate a self-consistent scheme for estimating the radius of gyration of the tethered polymer. This is shown in measurements of both hyaluronic acid and poly(ethylene glycol) chains.
Electromagnetic diode based on photonic crystal cavity with embedded highly dispersive meta-interface
Authors: Chen Yongqiang , Dong Lijuan , Xu Xiaohu , Jiang Jun , Shi Yunlong
Published: December 2017

In this paper, we propose a scheme for subwavelength electromagnetic diodes by employing a photonic crystal (PC) cavity with embedded electromagnetically induced-transparency (EIT)-like highly dispersive meta-interface. A nonreciprocal response, with 21.5 dB transmission light contrast and 12.3 dBm working power, is conceptually demonstrated in a microstrip transmission line system with asymmetric absorption and nonlinear medium inclusion. Such high-contrast transmission and relatively low-threshold diode action stem from the composite PC-EIT mechanism. This mechanism not only possesses a large quality factor and strong localization of fields but also does not enlarge the device volume and drastically reduce transmittance. Our findings should be beneficial for the design of new and practical metamaterial-enabled nonlinear devices.
Digitally controlled analog proportional-integral-derivative (PID) controller for high-speed scanning probe microscopy
Authors: Dukic Maja , Todorov Vencislav , Andany Santiago , Nievergelt Adrian P. , Yang Chen , Hosseini Nahid , Fantner Georg E.
Published: December 2017

Nearly all scanning probe microscopes (SPMs) contain a feedback controller, which is used to move the scanner in the direction of the z-axis in order to maintain a constant setpoint based on the tip-sample interaction. The most frequently used feedback controller in SPMs is the proportional-integral (PI) controller. The bandwidth of the PI controller presents one of the speed limiting factors in high-speed SPMs, where higher bandwidths enable faster scanning speeds and higher imaging resolution. Most SPM systems use digital signal processor-based PI feedback controllers, which require analog-to-digital and digital-to-analog converters. These converters introduce additional feedback delays which limit the achievable imaging speed and resolution. In this paper, we present a digitally controlled analog proportional-integral-derivative (PID) controller. The controller implementation allows tunability of the PID gains over a large amplification and frequency range, while also providing precise control of the system and reproducibility of the gain parameters. By using the analog PID controller, we were able to perform successful atomic force microscopy imaging of a standard silicon calibration grating at line rates up to several kHz.
Observation of trapped-electron-mode microturbulence in reversed field pinch plasmas
Authors: Duff J. R. , Williams Z. R. , Brower D. L. , Chapman B. E. , Ding W. X. , Pueschel M. J. , Sarff J. S. , Terry P. W.
Published: December 2017

Density fluctuations in the large-density-gradient region of improved confinement Madison Symmetric Torus reversed field pinch (RFP) plasmas exhibit multiple features that are characteristic of the trapped-electron mode (TEM). Core transport in conventional RFP plasmas is governed by magnetic stochasticity stemming from multiple long-wavelength tearing modes. Using inductive current profile control, these tearing modes are reduced, and global confinement is increased to that expected for comparable tokamak plasmas. Under these conditions, new short-wavelength fluctuations distinct from global tearing modes appear in the spectrum at a frequency of f ∼ 50 kHz, which have normalized perpendicular wavenumbers k⊥ρs≲0.2 and propagate in the electron diamagnetic drift direction. They exhibit a critical-gradient threshold, and the fluctuation amplitude increases with the local electron density gradient. These characteristics are consistent with predictions from gyrokinetic analysis using the Gene code, including increased TEM turbulence and transport from the interaction of remnant tearing magnetic fluctuations and zonal flow.
Effect of Cd doping on magnetocaloric effect and critical behavior analysis on perovskite Nd1−xCdxMnO3 (x = 0, 0.1, 0.2, 0.3, and 0.4) manganite polycrystals
Authors: Saravanan C. , Thiyagarajan R. , Manikandan K. , Sathiskumar M. , Kanjariya P. V. , Bhalodia J. A. , Arumugam S.
Published: December 2017

We report the doping effect of divalent cation Cd2+ at Nd-site of intermediate bandwidth manganite system NdMnO3 through the temperature- and magnetic field-dependent magnetization measurements. The parent compound shows paramagnetic-antiferromagnetic transition at 56 K, whereas Cd doped samples show the paramagnetic-ferromagnetic transition with fluctuating TC. During this transition, Nd1−xCdxMnO3 (x = 0.1 and 0.2) samples exhibit first order nature, whereas Nd1−xCdxMnO3 (x = 0.3 and 0.4) samples exhibit second order nature. It confirms a crossover from first order transition to second order transition while x = 0.2 to x = 0.3. By having first order transition, x = 0.2 sample exhibits high magnetic entropy change of 3.62 J kg−1 K−1 for the magnetic field change of 5 T out of all compositions. By having second order transitions, x = 0.4 sample exhibits a high relative cooling power of 319.71 J kg−1 for the magnetic field change of 5 T out of all the compositions. The critical behavior of second order transition of x = 0.3 and 0.4 samples has been analyzed using Arrott and Kouvel-Fisher plots. The estimated critical exponents of these samples are nearly matched with the mean free model, which can be explained by the existence of dipole-dipole interaction by the Cd doping which strengthens long range ferromagnetic interactions between the spins.
Communication: Counter-ion solvation and anomalous low-angle scattering in salt-free polyelectrolyte solutions
Authors: Chremos Alexandros , Douglas Jack F.
Published: December 2017

We investigate the influence of counter-ion solvation on the homogeneity of salt-free polyelectrolyte solutions based on a coarse-grained model that includes an explicit solvent. We show that the solvation of the counter-ions can cause a transformation between a nearly homogeneous to a non-uniform polymer solution, in which there is both a chain clustering and the formation of large charge-free domains, i.e., “voids.” The emergence of these heterogeneous structures induced by counter-ion solvation is accompanied by the localization and formation of counter-ion rich domains that are symptomatic of emergent effective long-range attractive interchain interactions.
Versatile electronic and magnetic properties of chemically doped 2D platinum diselenide monolayers: A first-principles study
Authors: Zulfiqar Muhammad , Li Geng , Zhao Yinchang , Nazir Safdar , Ni Jun
Published: December 2017

First-principles calculations have been performed to study the chemically doped platinum diselenide (PtSe2) monolayers. We examine the stability of different doping sites by calculating the formation energy. The different electronic and magnetic characters originate from hybridization between the dopants and nearest local atoms. Exceptional electronic and magnetic characters are observed in the B-, P-, Li-, and Ca-doped cases because of doping site independence. The magnetic behavior of the dopant atoms is found to be complex because of interplay between strong structural relaxation, spin lattice coupling, and crystal field splitting. More interestingly, the ferromagnetic half metallic character obtained in B- and N-doped cases, expected to be very useful because of large half metallic energy bandgap. The interaction between dopants is analyzed as a function of their separation, showing that substitution typically counteracts spin polarization. The long range ferromagnetic behavior can be established with improved stability which suggest the high magnetic transition temperatures, found for the B-, F-, N-, P-, and Li-doped at Pt sites which make them potential candidate for applications in electronic devices as well as in spintronics.
Possible effect of static surface disorder on diffractive scattering of H2 from Ru(0001): Comparison between theory and experiment
Authors: Kroes G. J. , Wijzenbroek Mark , Manson J. R.
Published: December 2017

Specific features of diffractive scattering of H2 from metal surfaces can serve as fingerprints of the reactivity of the metal towards H2, and in principle theory-experiment comparisons for molecular diffraction can help with the validation of semi-empirical functionals fitted to experiments of sticking of H2 on metals. However, a recent comparison of calculated and Debye-Waller (DW) extrapolated experimental diffraction probabilities, in which the theory was done on the basis of a potential energy surface (PES) accurately describing sticking to Ru(0001), showed substantial discrepancies, with theoretical and experimental probabilities differing by factors of 2 and 3. We demonstrate that assuming a particular amount of random static disorder to be present in the positions of the surface atoms, which can be characterized through a single parameter, removes most of the discrepancies between experiment and theory. Further improvement might be achievable by improving the accuracy of the DW extrapolation, the model of the H2 rotational state distribution in the experimental beams, and by fine-tuning the PES. However, the question of whether the DW model is applicable to attenuation of diffractive scattering in the presence of a sizable van der Waals well (depth ≈ 50 meV) should also receive attention, in addition to the question of whether the amount of static surface disorder effectively assumed in the modeling by us could have been present in the experiments.
Communication: Reactivity borrowing in the mode selective chemistry of H + CHD3 → H2 + CD3
Authors: Ellerbrock Roman , Manthe Uwe
Published: December 2017

Quantum state-resolved reaction probabilities for the H + CHD3 → H2 + CD3 reaction are calculated by accurate full-dimensional quantum dynamics calculations using the multi-layer multi-configurational time-dependent Hartree approach and the quantum transition state concept. Reaction probabilities of various ro-vibrational states of the CHD3 reactant are investigated for vanishing total angular momentum. While the reactivity of the different vibrational states of CHD3 mostly follows intuitive patterns, an unusually large reaction probability is found for CHD3 molecules triply excited in the CD3 umbrella-bending vibration. This surprising reactivity can be explained by a Fermi resonance-type mixing of the single CH-stretch excited and the triple CD3 umbrella-bend excited vibrational states of CHD3. These findings show that resonant energy transfer can significantly affect the mode-selective chemistry of CHD3 and result in counter-intuitive reactivity patterns.
Turbulent statistics in flow field due to interaction of two plane parallel jets
Authors: Bisoi Mukul , Das Manab Kumar , Roy Subhransu , Patel Devendra Kumar
Published: December 2017

Turbulent characteristics of flow fields due to the interaction of two plane parallel jets separated by the jet width distance are studied. Numerical simulation is carried out by large eddy simulation with a dynamic Smagorinsky model for the sub-grid scale stresses. The energy spectra are observed to follow the −5/3 power law for the inertial sub-range. A proper orthogonal decomposition study indicates that the energy carrying large coherent structures is present close to the nozzle exit. It is shown that these coherent structures interact with each other and finally disintegrate into smaller vortices further downstream. The turbulent fluctuations in the longitudinal and lateral directions are shown to follow a similarity. The mean flow at the same time also maintains a close similarity. Prandtl’s mixing length, the Taylor microscale, and the Kolmogorov length scales are shown along the lateral direction for different downstream locations. The autocorrelation in the longitudinal and transverse directions is seen to follow a similarity profile. By plotting the probability density function, the skewness and the flatness (kurtosis) are analyzed. The Reynolds stress anisotropy tensor is calculated, and the anisotropy invariant map known as Lumley’s triangle is presented and analyzed.
Sensing based on the energy transfer in a hybrid plasmonic-molecular system: The orientation effect of the donor and acceptor molecules
Authors: Daneshfar Nader , Yavari Asghar
Published: December 2017

In the present study, the energy transfer between two molecules (the donor-acceptor molecular pair) near a plasmonic nanoparticle is investigated and discussed by taking into account the orientations of donor and acceptor dipoles. We show that the energy spectrum is strongly sensitive to the angular position of the donor and acceptor molecules. It is found that by varying the orientation of the donor or the acceptor molecule, the intensity and position of the resonance peaks will change. We also show that the transferred energy from the donor to the acceptor is affected by the embedding medium, the metal type of nanoparticle, and the intermolecular distance, which is needed to design and construction of devices based on the energy transfer and can be used for sensing devices.
Introduction to focus issue: Synchronization in large networks and continuous media—data, models, and supermodels
Authors: Duane Gregory S. , Grabow Carsten , Selten Frank , Ghil Michael
Published: December 2017

The synchronization of loosely coupled chaotic systems has increasingly found applications to large networks of differential equations and to models of continuous media. These applications are at the core of the present Focus Issue. Synchronization between a system and its model, based on limited observations, gives a new perspective on data assimilation. Synchronization among different models of the same system defines a supermodel that can achieve partial consensus among models that otherwise disagree in several respects. Finally, novel methods of time series analysis permit a better description of synchronization in a system that is only observed partially and for a relatively short time. This Focus Issue discusses synchronization in extended systems or in components thereof, with particular attention to data assimilation, supermodeling, and their applications to various areas, from climate modeling to macroeconomics.
When linearity prevails over hierarchy in syntax
Authors: Willer Gold Jana , Arsenijević Boban , Batinić Mia , Becker Michael , Čordalija Nermina , Kresić Marijana , Leko Nedžad , Marušič Franc Lanko , Milićev Tanja , Milićević Nataša , Mitić Ivana , Peti-Stantić Anita , Stanković Branimir , Šuligoj Tina , Tušek Jelena , Nevins Andrew
Published: December 2017

Significance

Syntactic distance is standardly measured hierarchically only by counting the nodes in a tree-like structure. The dominance of hierarchy over the other logically possible measure of distance—e.g., counting words in a linear order—stems from a large body of research. We show a strong preference for the linear strategy in coordination structures in South Slavic languages, with a design comparing agreement controllers that can come either before or after their target. A large-scale study over six geographically and linguistically distinct varieties discovered remarkable uniformity in this preference. Variation discovered was mostly intraindividual, strongly suggesting that a language can entertain synchronous “multiple grammars,” the most striking of which is the one requiring direct reference to linear order.
L1 retrotransposon antisense RNA within ASAR lncRNAs controls chromosome-wide replication timing
Authors: Platt Emily J. , Smith Leslie , Thayer Mathew J.
Published: December 2017

Mammalian cells replicate their chromosomes via a temporal replication program. The ASAR6 and ASAR15 genes were identified as loci that when disrupted result in delayed replication and condensation of entire human chromosomes. ASAR6 and ASAR15 are monoallelically expressed long noncoding RNAs that remain associated with the chromosome from which they are transcribed. The chromosome-wide effects of ASAR6 map to the antisense strand of an L1 retrotransposon within ASAR6 RNA, deletion or inversion of which delayed replication of human chromosome 6. Furthermore, ectopic integration of ASAR6 or ASAR15 transgenes into mouse chromosomes resulted in delayed replication and condensation, an increase in H3K27me3, coating of the mouse chromosome with ASAR RNA, and a loss of mouse Cot-1 RNA expression in cis. Targeting the antisense strand of the L1 within ectopically expressed ASAR6 RNA restored normal replication timing. Our results provide direct evidence that L1 antisense RNA plays a functional role in chromosome-wide replication timing of mammalian chromosomes.
PGA: post-GWAS analysis for disease gene identification
Authors: Lin Jhih-Rong , Jaroslawicz Daniel , Cai Ying , Zhang Quanwei , Wang Zhen , Zhang Zhengdong D
Published: December 2017

Although the genome-wide association study (GWAS) is a powerful method to identify disease-associated variants, it does not directly address the biological mechanisms underlying such genetic association signals. Here, we present PGA, a Perl- and Java-based program for post-GWAS analysis that predicts likely disease genes given a list of GWAS-reported variants. Designed with a command line interface, PGA incorporates genomic and eQTL data in identifying disease gene candidates and uses gene network and ontology data to score them based upon the strength of their relationship to the disease in question.

Availability and implementation

http://zdzlab.einstein.yu.edu/1/pga.html

Supplementary information

Supplementary data are available at Bioinformatics online.
An Interpretable Machine Learning Model for Accurate Prediction of Sepsis in the ICU
Authors: Nemati Shamim , Holder Andre , Razmi Fereshteh , Stanley Matthew D. , Clifford Gari D. , Buchman Timothy G.
Published: December 2017

Objectives:

Sepsis is among the leading causes of morbidity, mortality, and cost overruns in critically ill patients. Early intervention with antibiotics improves survival in septic patients. However, no clinically validated system exists for real-time prediction of sepsis onset. We aimed to develop and validate an Artificial Intelligence Sepsis Expert algorithm for early prediction of sepsis.

Design:

Observational cohort study.

Setting:

Academic medical center from January 2013 to December 2015.

Patients:

Over 31,000 admissions to the ICUs at two Emory University hospitals (development cohort), in addition to over 52,000 ICU patients from the publicly available Medical Information Mart for Intensive Care-III ICU database (validation cohort). Patients who met the Third International Consensus Definitions for Sepsis (Sepsis-3) prior to or within 4 hours of their ICU admission were excluded, resulting in roughly 27,000 and 42,000 patients within our development and validation cohorts, respectively.

Interventions:

None.

Measurements and Main Results:

High-resolution vital signs time series and electronic medical record data were extracted. A set of 65 features (variables) were calculated on hourly basis and passed to the Artificial Intelligence Sepsis Expert algorithm to predict onset of sepsis in the proceeding T hours (where T = 12, 8, 6, or 4). Artificial Intelligence Sepsis Expert was used to predict onset of sepsis in the proceeding T hours and to produce a list of the most significant contributing factors. For the 12-, 8-, 6-, and 4-hour ahead prediction of sepsis, Artificial Intelligence Sepsis Expert achieved area under the receiver operating characteristic in the range of 0.83–0.85. Performance of the Artificial Intelligence Sepsis Expert on the development and validation cohorts was indistinguishable.

Conclusions:

Using data available in the ICU in real-time, Artificial Intelligence Sepsis Expert can accurately predict the onset of sepsis in an ICU patient 4–12 hours prior to clinical recognition. A prospective study is necessary to determine the clinical utility of the proposed sepsis prediction model.
Fractional microablative CO2 laser in breast cancer survivors affected by iatrogenic vulvovaginal atrophy after failure of nonestrogenic local treatments: a retrospective study
Authors: Pagano Tiziana , De Rosa Pasquale , Vallone Roberta , Schettini Francesco , Arpino Grazia , Giuliano Mario , Lauria Rossella , De Santo Irene , Conforti Alessandro , Gallo Alessandra , Nazzaro Giovanni , De Placido Sabino , Locci Mariavittoria , De Placido Giuseppe
Published: December 2017

Objective:

Vulvovaginal atrophy (VVA) is a condition frequently observed in menopause. Its symptoms can significantly affect the quality of life of patients. Since VVA is related to estrogen deficiency, chemotherapy and hormone therapy for breast cancer (BC) might cause VVA by inducing menopause. Given the lack of effective treatment for VVA in BC survivors, we retrospectively evaluated the efficacy and tolerability of fractional microablative CO2 laser therapy in these patients.

Methods:

We treated 82 BC survivors with three cycles of CO2 laser after failure of topical nonestrogenic therapy. The severity of symptoms was assessed with a visual analog scale (VAS) at baseline and after completion of laser therapy. Differences in mean VAS scores of each symptom before and after treatment were assessed with multiple t tests for pairwise comparisons. Multivariate analyses were used to adjust the final mean scores for the main confounding factors.

Results:

Pre versus post-treatment differences in mean VAS scores were significant for sensitivity during sexual intercourse, vaginal dryness, itching/stinging, dyspareunia and dysuria (P < 0.001 for all), bleeding (P = 0.001), probe insertion (P = 0.001), and movement-related pain (P = 0.011). Multivariate analyses confirmed that results were significant, irrespective of patients’ age and type of adjuvant therapy.

Conclusion:

This study shows that CO2 laser treatment is effective and safe in BC patients with iatrogenic menopause. However, the optimal number of cycles to administer and the need for retreatment remain to be defined. Prospective trials are needed to compare CO2 laser therapy with therapeutic alternatives.
Efficacy of Tensed and Straight Free Jejunum Transfer for the Reduction of Postoperative Dysphagia
Authors: Tachibana Satsuki , Miyamoto Shimpei , Goto Takahiro , Ishida Katsuhiro , Iida Takuya , Okazaki Mutsumi , Yoshida Sei , Nomura Shogo , Hayashi Ryuichi , Sakuraba Minoru
Published: December 2017

Background:

Free jejunal transfer (FJT) is a standard method of reconstruction after total pharyngo-laryngo-cervical esophagectomy (TPLE) in patients with advanced head and neck cancer. However, it is related to various degrees of postoperative swallowing dysfunction. This study aimed to assess whether the tensed and straight FJT method results in a reduced rate of postoperative dysphagia compared with historical controls.

Methods:

Patients who were undergoing FJT after TPLE for squamous cell carcinoma of the hypopharynx or cervical esophagus were enrolled. The primary endpoint was the rate of not developing dysphagia within 6 months of the surgery, and we compared this value with that obtained from historical data of patients who underwent FJT. The secondary endpoint was the rate of developing surgical complications.

Results:

Although 128 patients were registered between August 2012 and July 2015, 7 were excluded based on the exclusion criteria. Of the remaining 121 patients, FJT with the craniocaudally tensed and straight method was performed in all patients. The rate of not developing dysphagia and its 95% confidence interval (CI) were 66.1% and 57.0–74.5%, respectively. The lower limit of the CI was higher than the prespecified threshold value of 50.0%. The rate of developing complications of total necrosis of the jejunum was 3.3%, cervical infection was 9.9%, and major anastomotic leakage was 4.1%.

Conclusions:

Our findings revealed that the proportion of postoperative dysphagia decreased in patients who underwent tensed and straight FJT. This method may become the standard surgical method in reconstruction of defects after TPLE.
Myelofibrosis‐Related Anemia
Authors: Naymagon Leonard , Mascarenhas John
Published: December 2017

Myelofibrosis (MF) is a clonal hematopoietic stem cell disorder characterized by pathological myeloproliferation and aberrant cytokine production resulting in progressive fibrosis, inflammation, and functional compromise of the bone marrow niche. Patients with MF develop splenomegaly (due to extramedullary hematopoiesis), hypercatabolic symptoms (due to overexpression of inflammatory cytokines), and anemia (due to bone marrow failure and splenic sequestration). MF remains curable only with allogeneic hematopoietic stem cell transplantation (ASCT), a therapy that few MF patients are deemed fit to undergo. The goals of treatment are thus often palliative. The approval of the JAK inhibitor ruxolitinib has done much to address the burden of splenomegaly and constitutional symptoms of patients with MF; however, therapy‐related anemia is often an anticipated downside. Anemia thus remains a challenge in the management of MF and represents a major unmet need. Intractable anemia depresses quality of life, portends poor outcomes, and can act to restrict access to palliative JAK inhibition in some patients. While therapies for MF‐related anemia do exist, they are limited in their efficacy, durability, and tolerability. Therapies currently in development promise improved anemia‐specific outcomes; however, are still early in the pathway to regulatory approval and regular clinical use. In this review, we will discuss established and emerging treatments for MF‐related anemia. We will give particular attention to developmental therapies which herald significant progress in the understanding and management of MF‐related anemia.
Cost Analysis of a Student-Run, Free Physical Therapy Clinic
Authors: Stickler Kellie , Sabus Carla , Denney Linda
Published: December 2017

Introduction.

Within many physical therapy education programs, service learning is essential to student development and often complements the institutional priorities of serving the community. Service learning experiences vary from local, institution-hosted clinics to international experiences. Although the benefits of service learning to the students and community have been widely reported, it is also important to appreciate the cost to implement and support a service learning clinic within an academic department. The purpose of this study was to determine the cost of running a student-run free physical therapy clinic for estimated labor costs calculated as wage opportunity cost, quantify equipment and infrastructure cost per patient, estimate facility cost, and derive an estimated cost of care delivery per patient.

Methods.

This retrospective study reviewed patient charts and clinic data from a student-run free clinic between January 2013 and December 2014. Both total outgoing cost and potential total cost were determined for this study. The total outgoing cost was determined by calculating equipment cost and cost of liability insurance. The potential total cost was determined by calculating volunteer hours, facility cost, and outgoing clinic costs.

Results.

In the 2-year study period, the clinic incurred a potential total cost of $68,405.40. However, the total outgoing cost of the clinic was $1,993.23 for 253 patient visits, which gives the clinic an average cost per visit of $7.64.

Discussion/Conclusion.

This study demonstrates the feasibility of a student-run, free physical therapy clinic through monetized gain for the community while enhancing students' skills. Furthermore, this study demonstrates a method to capture quantifiable monetary cost and benefit to program stakeholders and the community.
Impact of New Medications and $4 Generic Programs on Overactive Bladder Treatment Among Older Adults in the United States, 2000–2015
Authors: Kinlaw Alan C. , Jonsson Funk Michele , Conover Mitchell M. , Pate Virginia , Markland Alayne D. , Wu Jennifer M.
Published: December 2017

Background:

Despite several new medications being Food and Drug Administration-approved for overactive bladder (OAB) and new prescription drug payment programs, there are limited population-based data regarding OAB medication use among older adults.

Objectives:

To examine: (1) impacts of new medications and $4 generic programs on time trends for OAB-related medication dispensing for older adults in the United States; (2) differences by age and sex; and (3) temporal changes in OAB-related medication payments.

Methods:

Using Truven Health Analytics’ Medicare Supplemental Database (2000–2015), we analyzed OAB-related medication claims for 9,477,061 Medigap beneficiaries age 65–104. We estimated dispensing rates (per 1000 person-months), assessed dispensing trends using interrupted time-series methods, compared dispensing rates by age and sex, and summarized payment trends.

Results:

From 2000 to 2015, 771,609 individuals filled 13,863,998 OAB-related prescriptions. During 2000–2007, 3 new extended-release medications became available (tolterodine, darifenacin, solifenacin), leading to increases in overall OAB-related dispensing rates by 19.1 (99% confidence interval, 17.0–21.2), a 92% increase since 2000; overall rates remained stable during 2008–2015. By 2015, the most common medications were oxybutynin (38%), solifenacin (20%), tolterodine (19%), and mirabegron (12%). Dispensing rates peaked at age 90 (rate, 53.4; 99% confidence interval, 53.1–53.7). Women had higher rates than men at all ages (average ratewomen−ratemen, 22.0). The gap between upper and lower percentiles of medication payments widened between 2008–2015; by 2015, 25% of reimbursed dispensed prescriptions had total payments exceeding $250.

Conclusions:

Medication-specific dispensing rates for OAB changed when new alternatives became available. Recent changes in utilization and cost of OAB medications have implications for clinical guidelines, pharmacoepidemiologic studies, and payment policies.
In vitro study of dentin hypersensitivity treated by whitlockite glass-ceramics
Authors: Juraski Amanda C.
Published: December 2017

The aim of this study is to evaluate the potential of a bioactive glass based on the 3CaO.P2O5-SiO2MgO-system and its glassceramics containing whitlockite on the remineralization of dentin as a possible treatment to dentin hypersensitivity. For that, 40 third molar human teeth were artificially demineralized and randomly distributed in 4 groups (n = 10): G1 - Negative Control (no treatment), G2 - Positive Control (treated by Bioglass® 45S5), G3 – BG (treated by bioactive glass based on 3CaO.P2O5-SiO2-MgOsystem), and G4 – BGC (treated by bioactive whitlockite glass-ceramics). After treatment, the samples were emerged in artificial saliva and stored for 7 days in a controlled temperature of 37ºC. After that, scanning electron microscopy (SEM) and atomic force microscopy (AFM) was used to evaluate samples morphology. The analysis confirmed the formation of hydroxyapatite on the surface of all the biomaterials studied, that in the dentine specimens treated by bioactive glass and whitlockite glas-ceramic most of the dentinal tubules were completely occluded.
Confidence modulates exploration and exploitation in value-based learning
Authors: Boldt Annika , Blundell Charles , De Martino Benedetto
Published: December 2017

Uncertainty is ubiquitous in cognitive processing, which is why agents require a precise handle on how to deal with the noise inherent in their mental operations. Previous research suggests that people possess a remarkable ability to track and report uncertainty, often in the form of confidence judgments. Here, we argue that humans use uncertainty inherent in their representations of value beliefs to arbitrate between exploration and exploitation. Such uncertainty is reflected in explicit confidence judgments. Using a novel variant of a multi-armed bandit paradigm, we studied how beliefs were formed and how uncertainty in the encoding of these value beliefs (belief confidence) evolved over time. We found that people used uncertainty to arbitrate between exploration and exploitation, reflected in a higher tendency towards exploration when their confidence in their value representations was low. We furthermore found that value uncertainty can be linked to frameworks of metacognition in decision making in two ways. First, belief confidence drives decision confidence—that is people’s evaluation of their own choices. Second, individuals with higher metacognitive insight into their choices were also better at tracing the uncertainty in their environment. Together, these findings argue that such uncertainty representations play a key role in the context of cognitive control.
False discovery rate estimation and heterobifunctional cross-linkers
Authors: Fischer Lutz , Rappsilber Juri
Published: December 2017

False discovery rate (FDR) estimation is a cornerstone of proteomics that has recently been adapted to cross-linking/mass spectrometry. Here we demonstrate that heterobifunctional cross-linkers, while theoretically different from homobifunctional cross-linkers, need not be considered separately in practice. We develop and then evaluate the impact of applying a correct FDR formula for use of heterobifunctional cross-linkers and conclude that there are minimal practical advantages. Hence a single formula can be applied to data generated from the many different non-cleavable cross-linkers.
Endogenous tagging reveals differential regulation of Ca2+channels at single AZs during presynaptic homeostatic potentiation and depression
Authors: Gratz Scott J. , Goel Pragya , Bruckner Joseph J. , Hernandez Roberto X. , Khateeb Karam , Macleod Gregory T. , Dickman Dion , O’Connor-Giles Kate M.
Published: December 2017

Neurons communicate through Ca2+-dependent neurotransmitter release at presynaptic active zones (AZs). Neurotransmitter release properties play a key role in defining information flow in circuits and are tuned during multiple forms of plasticity. Despite their central role in determining neurotransmitter release properties, little is known about how Ca2+channel levels are modulated to calibrate synaptic function. We used CRISPR to tag theDrosophilaCaV2 Ca2+ channel Cacophony (Cac) and investigated the regulation of endogenous Ca2+channels during homeostatic plasticity in males in which all endogenous Cac channels are tagged. We found that heterogeneously distributed Cac is highly predictive of neurotransmitter release probability at individual AZs and differentially regulated during opposing forms of presynaptic homeostatic plasticity. Specifically, Cac levels at AZ are increased during chronic and acute presynaptic homeostatic potentiation (PHP), and live imaging during acute expression of PHP reveals proportional Ca2+channel accumulation across heterogeneous AZs. In contrast, endogenous Cac levels do not change during presynaptic homeostatic depression (PHD), implying that the reported reduction in Ca2+influx during PHD is achieved through functional adaptions to pre-existing Ca2+channels. Thus, distinct mechanisms bi-directionally modulate presynaptic Ca2+levels to maintain stable synaptic strength in response to diverse challenges, with Ca2+channel abundance providing a rapidly tunable substrate for potentiating neurotransmitter release over both acute and chronic timescales.