bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of Electronic versus Paper-Based Recording before EHR Implementation on Health Care Professionals' Perceptions of EHR Use, Data Quality, and Data Reuse
Authors: Joukes Erik , de Keizer Nicolette , de Bruijne Martine , Abu-Hanna Ameen , Cornet Ronald
Published: March 2019

Background The implementation of an electronic health record (EHR) with structured and standardized recording of patient data can improve data quality and reusability. Whether and how users perceive these advantages may depend on the preimplementation situation.

Objective To determine whether the influence of implementing a structured and standardized EHR on perceived EHR use, data quality, and data reuse differed for users working with paper-based records versus a legacy EHR before implementation.

Methods We used an electronic questionnaire to measure users' perception before implementation (2014), expected change, and perceived change after implementation (2016) on three themes. We included all health care professionals in two university hospitals in the Netherlands. Before jointly implementing the same structured and standardized EHR, one hospital used paper-based records and the other a legacy EHR. We compared perceptions before and after implementation for both centers. Additionally, we compared expected benefit with perceived benefit.

Results We received 7,611 responses (4,537 before and 3,074 after implementation) of which 5,707 (75%) were from professionals reading and recording patient data. A total of 975 (13%) professionals responded to both before and after implementation questionnaires. In the formerly paper-based center staff perceived improvement in all themes after implementation. The legacy EHR center experienced deterioration of perceived EHR use and data reuse, and only one improvement in EHR use. In both centers, for half of the aspects at least 45% of responders experienced results worse than expected preimplementation.

Conclusion Our results indicate that the preimplementation recording practice impacts the perceived effect of the implementation of a structured and standardized EHR. For almost half of the respondents the new EHR did not meet their expectations. Especially legacy EHR centers need to investigate the expectations as these might be different and less clear cut than those in paper-based centers. These expectations need to be addressed appropriately to achieve a successful implementation.
Pediatric Residency Graduates Preparedness for Neonatal-Perinatal Medicine Fellowship: The Perspective of First-Year Fellows
Authors: Korbel Lindsey , Backes Carl H. , Rivera Brian K. , Mitchell Courtney C. , Carbajal Melissa M. , Reber Kristina , Bonachea Elizabeth M.
Published: March 2019

Objective This study aimed to report on Neonatal-Perinatal Medicine (NPM) fellows' views of self-preparedness upon starting postresidency training.

Study Design We conducted a national survey of first-year NPM fellows in the United States. The validated survey had five major areas: professionalism, psychomotor ability, independence/graduated responsibility, clinical evaluation, and academia. Survey responses were analyzed using descriptive statistics, and the free-text answers were categorized.

Results Of 228 potential first-year NPM fellows, 140 (61%) initially responded to the survey. Overall, the fellows perceived themselves positively in professionalism and independence/graduated responsibility domains. Marked variability was observed in perceived preparedness in psychomotor ability, with confidence in neonatal intubation and arterial line placement of 86 and 49%, respectively. Lack of confidence in performing neonatal intubation procedures correlates with lack of attempts. The majority (75%) of fellows reported being interested in academia, but less than half felt capable of writing an article.

Conclusion First-year NPM fellows identified deficiencies in the domains of psychomotor ability and academia. Residency and fellowship programs should partner to address these deficiencies.
Incremental Cost of Prematurity by Week of Gestational Age
Authors: Walsh Eileen , Li Sherian , Black Libby , Kuzniewicz Michael
Published: March 2019

Objective This study was aimed to compare health care costs and utilization at birth through 1 year, between preterm and term infants, by week of gestation.

Methods A cross-sectional study of infants born at ≥ 23 weeks of gestational age (GA) at Kaiser Permanente Northern California facilities between 2000 and 2011, using outcomes data from an internal neonatal registry and cost estimates from an internal cost management database. Adjusted models yielded estimates for cost differences for each GA group.

Results Infants born at 25 to 37 weeks incur significantly higher birth hospitalization costs and experience significantly more health care utilization during the initial year of life, increasing progressively for each decreasing week of gestation, when compared with term infants. Among all very preterm infants (≤ 32 weeks), each 1-week decrease in GA is associated with incrementally higher rates of mortality and major morbidities.

Conclusion We provide estimates of potential cost savings that could be attributable to interventions that delay or prevent preterm delivery. Cost differences were most extreme at the lower range of gestation (≤ 30 weeks); however, infants born moderately preterm (31–36 weeks) also contribute substantially to the burden, as they represent a higher proportion of total births.
Ion-induced nanopatterning of silicon: Toward a predictive model
Authors: Norris Scott A. , Aziz Michael J.
Published: March 2019

We review recent progress toward the development of predictive models of ion-induced pattern formation on room-temperature silicon, with a particular emphasis on efforts to eliminate fit parameters in the linear regime by means of experimental measurements or atomistic simulations. Analytical approaches considered include “mechanistic” models of the impact-induced collision cascade, the Crater Function Framework, and continuum treatments of ion-induced stress and viscous flow. Parameter evaluation methods include molecular dynamics and binary collision approximation simulations, as well as wafer curvature measurements and grazing incidence small-angle x-ray scattering. Mathematical detail is provided in the context of key results from pattern formation theory, which are also briefly summarized.
Flexible radiofrequency filters based on highly conductive graphene assembly films
Authors: Zhou Wenqing , Liu Chengguo , Song Rongguo , Zeng Xianci , Li Bao-Wen , Xia Wei , Zhang Jingwei , Huang Guan-Long , Wu Zhi Peng , He Daping
Published: March 2019

We demonstrate a flexible radiofrequency filter based on graphene assembly films with a high conductivity up to 106 S/m and a thickness of 10 μm. The flexible high-conductivity graphene film (HCGF) used in the filter has a fifth-order low-pass Chebyshev frequency response, and it operates at 3.6 GHz with a 0.82 dB in-band maximum insertion loss and 26.21 dB insertion loss at 5 GHz. Such performance observed in the HCGF-based flexible filters is comparable to that of commercial copper-based filters in passband and roll-off. The HCGF exhibits good mechanical flexibility even after 200 cycles of bending. Nearly no mechanical failure or performance degradation occurs during 20 cycles of 0°–50° bending for the flexible HCGF filter. Our results suggest that the flexible HCGF filter has good repetitive bending stability. This makes this type of filter suitable for future applications in flexible wireless communication.
Enhanced permeability dielectric FeCo/Al2O3 multilayer thin films with tailored properties deposited by magnetron sputtering on silicon
Authors: Falub Claudiu V. , Pietambaram Srinivas V. , Yildirim Oguz , Meduňa Mojmír , Caha Ondrej , Hida Rachid , Zhao Xue , Ambrosini Jan , Rohrmann Hartmut , Hug Hans J.
Published: March 2019

We have studied the structural and magnetic properties of enhanced-permeability-dielectric FeCo/Al2O3-multilayer thin films deposited on 8"-Si wafers in an industrial magnetron sputtering system. The EPD-multilayers consist of 25 periods of alternating nanometer-thick FeCo-layers deposited by DC sputtering from a Fe60Co40 target and Al2O3-interlayers deposited by RF sputtering from an Al2O3 target. We tuned the magnetic properties of these thin films by varying the thickness of FeCo-layers from 1.1nm to 2.1nm, while the thickness of Al2O3-interlayers remained unchanged (3.5nm). The formation of layers of disconnected FeCo-nanoparticles separated by an Al2O3-matrix was revealed by grazing incidence small angle X-ray-scattering. Further insight into the microstructure of these layers was obtained from X-ray-reflectivity, highly asymmetric-X-ray-diffraction and non-coplanar grazing-incidence-diffraction. The Fe/Co ratio in the FeCo-layers obtained from X-ray-fluorescence measurements was (59±1)/(41±1), which is in very good agreement with the nominal value in the Fe60Co40 target. Using the standing wave technique we found that most of the Fe and Co atoms were located inside the polycrystalline grains, except for a small fraction that diffused into the Al2O3-matrix, and that the thinner the FeCo-layers thickness the higher the fraction of diffused atoms with respect to those in the grains. Zero-field-cooled, field-cooled, and hysteresis (B-H) and (M-H) measurements showed that the FeCo/Al2O3-multilayers with FeCo-layers thinner than 1.7–1.8 nm exhibit superparamagnetic behavior (no coercivity and remanence) at room temperature with peak relative low-field permeability up to 887. By exceeding this critical thickness, the neighboring FeCo-aggregates started to coalesce, and this led to the ferromagnetic behavior revealed by a finite coercivity and remanence in the hysteresis loops.
Phosphorus-doped (113) CVD diamond: A breakthrough towards bipolar diamond devices
Authors: Pinault-Thaury Marie-Amandine , Temgoua Solange , Gillet Rémi , Bensalah Hakima , Stenger Ingrid , Jomard François , Issaoui Riadh , Barjon Julien
Published: March 2019

Among wide bandgap semiconductors, diamond presents physical properties particularly suited for high performance power electronic devices. Growth and doping of chemical vapor deposited (CVD) diamond have been mainly optimized in the conventional (100) crystal orientation, highly studied on (111) surfaces and recently initiated on (113). This last orientation seems very promising, as is shown for intrinsic and p-type doped diamonds. In this work, we report the growth of CVD phosphorus doped diamond films on (113)-oriented substrates. The (113) homoepitaxial layers present a phosphorus content in the range of 7.2 × 1016 up to 4.5 × 1019 at/cm3 for thicknesses between 0.6 μm and 4 μm. The high quality and the full incorporation of phosphorus into donor sites found for the (113) crystal orientation open new architecture possibilities for bipolar diamond devices.
FORC study of the ferromagnetic impurities in Na and K feldspars of “El Realejo” mine
Authors: Montiel-Anaya Jose Antonio , Franco Victorino
Published: March 2019

Feldspar is a Na-K-Ca-Al tectosilicate, generally poor in iron or other elements with large magnetic moments. Being the most abundant constituent minerals in Earth’s crust, feldspars are technologically used in a broad variety of applications, which include glass-manufacturing, fabrication of ceramics elements, fillers in paintings, enamels, floors, etc. However, most applications require the absence (or minimization) of Fe inclusions, being this a very relevant factor that controls the price of the mineral. Typically, Fe content in the mineral produced at a mine is determined by chemical analysis, which implies an off-site test and small sampling volume. Separation of magnetic inclusions is usually made by crushing the rocks and applying a magnetic field gradient that, in combination with gravity, guides the magnetic particles out from the production line. In this work we use FORC to determine the content of the magnetic phases and show that the conventional separation methods used in the mine, which indirectly affect the final price of the product, are selective in the extraction of magnetic particles, as evidenced by the different FORC distribution of the natural rock and that of the separated particles.
Identification of divacancy and silicon vacancy qubits in 6H-SiC
Authors: Davidsson Joel , Ivády Viktor , Armiento Rickard , Ohshima Takeshi , Son N. T. , Gali Adam , Abrikosov Igor A.
Published: March 2019

Point defects in semiconductors are relevant for use in quantum technologies as room temperature qubits and single photon emitters. Among suggested defects for these applications are the negatively charged silicon vacancy and the neutral divacancy in SiC. The possible nonequivalent configurations of these defects have been identified in 4H-SiC, but for 6H-SiC, the work is still in progress. In this paper, we identify the different configurations of the silicon vacancy and the divacancy defects to each of the V1-V3 and the QL1-QL6 color centers in 6H-SiC, respectively. We accomplish this by comparing the results from ab initio calculations with experimental measurements for the zero-phonon line, hyperfine tensor, and zero-field splitting.
Refinement of thermostated molecular dynamics using backward error analysis
Authors: Silveira Ana J. , Abreu Charlles R. A.
Published: March 2019

Kinetic energy equipartition is a premise for many deterministic and stochastic molecular dynamics methods that aim at sampling a canonical ensemble. While this is expected for real systems, discretization errors introduced by the numerical integration may lead to deviations from equipartition. Fortunately, backward error analysis allows us to obtain a higher-order estimate of the quantity that is actually subject to equipartition. This is related to a shadow Hamiltonian, which converges to the specified Hamiltonian only when the time-step size approaches zero. This paper deals with discretization effects in a straightforward way. With a small computational overhead, we obtain refined versions of the kinetic and potential energies, whose sum is a suitable estimator of the shadow Hamiltonian. Then, we tune the thermostatting procedure by employing the refined kinetic energy instead of the conventional one. This procedure is shown to reproduce a canonical ensemble compatible with the refined system, as opposed to the original one, but canonical averages regarding the latter can easily be recovered by reweighting. Water, modeled as a rigid body, is an excellent test case for our proposal because its numerical stability extends up to time steps large enough to yield pronounced discretization errors in Verlet-type integrators. By applying our new approach, we were able to mitigate discretization effects in equilibrium properties of liquid water for time-step sizes up to 5 fs.
Upgrade to the MAPS neutron time-of-flight chopper spectrometer
Authors: Ewings R. A. , Stewart J. R. , Perring T. G. , Bewley R. I. , Le M. D. , Raspino D. , Pooley D. E. , Škoro G. , Waller S. P. , Zacek D. , Smith C. A. , Riehl-Shaw R. C.
Published: March 2019

The MAPS direct geometry time-of-flight chopper spectrometer at the ISIS pulsed neutron and muon source has been in operation since 1999, and its novel use of a large array of position-sensitive neutron detectors paved the way for a later generations of chopper spectrometers around the world. Almost two decades of experience of user operations on MAPS, together with lessons learned from the operation of new generation instruments, led to a decision to perform three parallel upgrades to the instrument. These were to replace the primary beamline collimation with supermirror neutron guides, to install a disk chopper, and to modify the geometry of the poisoning in the water moderator viewed by MAPS. Together, these upgrades were expected to increase the neutron flux substantially, to allow more flexible use of repetition rate multiplication and to reduce some sources of background. Here, we report the details of these upgrades and compare the performance of the instrument before and after their installation as well as to Monte Carlo simulations. These illustrate that the instrument is performing in line with, and in some respects in excess of, expectations. It is anticipated that the improvement in performance will have a significant impact on the capabilities of the instrument. A few examples of scientific commissioning are presented to illustrate some of the possibilities.
Hybrid improper ferroelectricity and possible ferroelectric switching paths in Sr3Hf2O7
Authors: Liu X. Q. , Lu J. J. , Chen B. H. , Zhang B. H. , Chen X. M.
Published: March 2019

Hybrid improper ferroelectricity, which is induced by the coupling of oxygen octahedral rotation and tilt in oxide materials, has great potential to create single-phase multiferroic materials with intrinsic electric field-controlled magnetism. Based on previous experiments with bi-layered Ruddlesden-Popper Sr-based materials, hybrid improper ferroelectricity in Sr3Hf2O7 was investigated by first-principle calculations in the present work. The results show that the ferroelectric A21am phase has the lowest energy among all possible phases, indicating that it is the ground state. The spontaneous polarization calculated by the Berry phase approach and Born effective charge model is approximately 4.6 μC/cm2, in agreement with those reported for other Sr-based compounds. Compared to Ca3Ti2O7, the smaller polarization of Sr3Hf2O7 is attributed to the negative contribution of the HfO2 layer to global polarization. The possible ferroelectric switching path was determined using the nudged elastic band method. The energy barriers of the two four-step paths across the non-polar Pbnm and Pnab phases are almost the same, and they are the lowest energies among all possible paths. Competition between these paths can help us understand complex phase transitions in analogous compounds. In summary, hybrid improper ferroelectricity was predicted in Sr3Hf2O7 for the first time, and the possible ferroelectric switching paths were determined.
High-frequency V-doped ZnO/SiC surface acoustic wave devices with enhanced electromechanical coupling coefficient
Authors: Fu Sulei , Wang Weibiao , Li Qi , Lu Zengtian , Chen Zhenglin , Luo Jingting , Shen Junyao , Wang Rui , Song Cheng , Zeng Fei , Pan Feng
Published: March 2019

The rapid development of large-volume and high-speed mobile communication systems has increased the demand for high-frequency and wide-band surface acoustic wave (SAW) devices. In this work, ZnO films and V-doped ZnO (V:ZnO) films with (0002) orientation were grown on SiC substrates using a magnetron sputtering method. High-frequency SAW resonators with the resonant frequency ranging from 4 GHz to 6 GHz were fabricated on the above structures. V:ZnO/SiC SAW resonators exhibited a significantly increased electromechanical coupling coefficient (K2) in the range of 2.80%–5.12%, in a wide normalized thickness range, which is more than a 75% increase compared to that of ZnO-based SAW resonators. Besides, the high quality factor Q ranging from 431 to 593 and an improvement in the figure of merit value were observed for the V:ZnO/SiC SAW resonators operating at 4–6 GHz. Finally, 4.58 GHz SAW filters using V:ZnO films with a larger bandwidth and a lower insertion loss were achieved. This work clearly shows that the ZnO/SiC SAW properties can be improved by V doping, and the V:ZnO/SiC structures have great potential for application in high-frequency and wide-band SAW filters.
Preparation and application of solid polymer electrolyte based on deep eutectic solvent
Authors: Luo Rubai , Jiang Haiying , Du Bin , Zhou Shisheng , Zhu Yuxiang
Published: March 2019

Deep eutectic solvent (DES) was prepared from choline chloride/1,3-butanediol (CHCl/BG). DES, 1-methyl-2-pyrrolidone (NMP) and poly-vinylidene fluoride (PVDF) was cross-linked and mixed to prepare a solid polymer electrolyte (SPE). The SPE was characterized by Fourier transform infrared spectroscopy (FTIR) and X-ray photoelectron spectroscopy (XPS). The goal was to identify major functional group and element composition. Results showed that SPE contained the C-N, C-O, C-H, C-Cl, C-F, N-C=O functional groups and oxygen atom, nitrogen atom, carbon atom, chlorine atom, fluorine atom. The DES was characterized by Transmission electron microscopy (TEM). The goal was to identify microscopic morphology. Results showed that DES is dominated by amorphous. The SPE was characterized by Scanning electron microscopy (SEM). The goal was to identify pore structure. Results showed that pore structure is dominated by amorphous. The SPE was characterized by X-ray diffraction (XRD) and Differential scanning calorimetry (DSC). The goal was to analyze the crystallinity of SPE. Results showed that heat treatment temperature and time increase resulted in a significant increase in crystallinity. Cyclic voltammetric measurements (CV) showed that the SPE has relatively good stability. The results demonstrated that when the weight ratio of CHCl: BG was 1:1, the conductivity of DES is best. Studies had shown that when the weight ratio of DES: PVDF: NMP was 1:1:4, the conductivity of SPE is best. Studies had shown that it optimum treatment temperature for SPE was 90°C for 6 minutes. The SPE had been applied to NO2 gas sensor.
Structural analysis of cubic boron nitride (111) films heteroepitaxially grown on diamond (111) substrates
Authors: Hirama Kazuyuki , Taniyasu Yoshitaka , Yamamoto Hideki , Kumakura Kazuhide
Published: March 2019

We investigate the structural properties of cubic boron nitride (c-BN) (111) films heteroepitaxially grown on diamond (111) substrates by ion-beam-assisted molecular beam epitaxy (MBE). Microstructures of the c-BN films depend on the growth temperature (Tg). At Tg above 750 °C, the single-domain epitaxial c-BN (111) films are formed. Higher Tg is effective for improving the surface flatness and suppressing stacking-fault formation on the (11-1) plane. The single-domain c-BN (111) films have nitrogen polarity, implying that C-B bonds are preferentially formed at the c-BN/diamond heterointerface. On the other hand, at low Tg, the c-BN films have a multi-domain structure with epitaxial and rotated domains. We propose a model for the single-domain formation of the heteroepitaxial c-BN (111) films.
Emergent dynamics of coordinated cells with time delays in a tissue
Authors: Pan Chiyu , Jiang Yuanren , Zhu Qunxi , Lin Wei
Published: March 2019

In this article, we investigate the emergence of tissue dynamics with time delays of diffusion. Such emergent dynamics, describing the tissue homeostasis, usually correspond to particular tissue functions, which are attracting a tremendous amount of attention from both communities of mathematical modeling and systems biology. Specifically, in addition to the within-cell genome dynamics and the diffusion among the cells, we consider several types of time delays of diffusion present in the coordinated cells. We establish several generalized versions of the “monotonicity condition” (MC), whose traditional version [I. Rajapakse and S. Smale, Proc. Natl. Acad. Sci. U.S.A. 114, 1462–1467 (2017)] guaranteed the stability of the equilibrium in a system of coordinated cells without time delay. Indeed, we find that one generalized MC we establish still guarantees the stability of the time-delayed system’s equilibrium, which corresponds to a formation of tissue functions depending primarily on individual genome dynamics but less on interacting structures and time delays of diffusion. We also find that, when the generalized MC is further relaxed, the system is able to sustain periodic oscillations, whose periods are verified to have delicate dependence with the selected time delays. These produced oscillations usually represent realistic behaviors of “alive” cells. We use several representative examples to demonstrate the usefulness of the established analytical conditions to the understanding of the emergent dynamics observed in computational models and in real systems as well.
Fast scrambling on sparse graphs
Authors: Bentsen Gregory , Gu Yingfei , Lucas Andrew
Published: March 2019

Significance

Are there bounds on quantum information processing and thermalization in many-body quantum systems? The fast-scrambling conjecture states that quantum information processing times must grow at least logarithmically with the number of degrees of freedom. We derive this result for generic systems. We discuss the nonuniversal relationship between scrambling and many-body quantum chaos, which is often used as a diagnostic for fast scrambling. We also find explicit examples of sparsely connected quantum systems which are fast scramblers, suggesting additional routes to experimentally testing the fast-scrambling conjecture in cold atomic gases. These results clarify for which information-processing tasks quantum black holes may be the fastest quantum systems.
A minimal-length approach unifies rigidity in underconstrained materials
Authors: Merkel Matthias , Baumgarten Karsten , Tighe Brian P. , Manning M. Lisa
Published: March 2019

Significance

What do a guitar string and a balloon have in common? They are both floppy unless rigidified by geometric incompatibility. The same kind of rigidity transition in underconstrained materials has more recently been discussed in the context of disordered biopolymer networks and models for biological tissues. Here, we propose a general approach to quantitatively describe such transitions. Based on a minimal length function, which scales linearly with intrinsic fluctuations in the system and quadratically with shear strain, we make concrete predictions about the elastic response of these materials, which we verify numerically and which are consistent with previous experiments. Finally, our approach may help develop methods that connect macroscopic elastic properties of disordered materials to their microscopic structure.
Connectional architecture of a mouse hypothalamic circuit node controlling social behavior
Authors: Lo Liching , Yao Shenqin , Kim Dong-Wook , Cetin Ali , Harris Julie , Zeng Hongkui , Anderson David J. , Weissbourd Brandon
Published: March 2019

Significance

How hypothalamic cellular heterogeneity maps onto circuit connectivity, and the relationship of this anatomical mapping to behavioral function, remain poorly understood. Here we systematically map the connectivity of estrogen receptor-1–expressing neurons in the ventromedial hypothalamus (VMHvl
Esr1
), which control aggression and related social behaviors, using multiple viral-genetic tracers. Rather than a simple feed-forward sensory-to-motor processing stream, we find high convergence (fan-in) and divergence (fan-out) in VMHvl
Esr1
inputs and projections, respectively, with massive feedback. However, outputs are split into two subpopulations that project either posteriorly, to premotor structures, or anteriorly back to the amygdala and hypothalamus. This fan-in/-out system architecture is consistent with “antenna” and “broadcasting” functions for VMHvl
Esr1
neurons, with the feedback pathway possibly controlling behavioral decisions and internal state.
Gliogenesis in the outer subventricular zone promotes enlargement and gyrification of the primate cerebrum
Authors: Rash Brian G. , Duque Alvaro , Morozov Yury M. , Arellano Jon I. , Micali Nicola , Rakic Pasko
Published: March 2019

Significance

The formation of cortical convolutions of primates, including humans, is one of the most important subjects in developmental neuroscience, but the underlying mechanisms—considered mostly solved toward the end of the 20th century—have become controversial in the last decade. Recent studies suggest that a stem cell zone called the outer subventricular zone (oSVZ) induces gyri to form directly through neurogenesis. Here, we provide evidence in macaque monkey demonstrating that oSVZ neurogenesis is actually complete before gyrification begins and that a major function of the oSVZ is to produce the glial cells associated with the rapid expansion and folding of the cortical surface.
Imaging flow cytometry facilitates multiparametric characterization of extracellular vesicles in malignant brain tumours
Authors: Ricklefs Franz L. , Maire Cecile L. , Reimer Rudolph , Dührsen Lasse , Kolbe Katharina , Holz Mareike , Schneider Enja , Rissiek Anne , Babayan Anna , Hille Claudia , Pantel Klaus , Krasemann Susanne , Glatzel Markus , Heiland Dieter Henrik , Flitsch Jörg , Martens Tobias , Schmidt Nils Ole , Peine Sven , Breakefield Xandra O. , Lawler Sean , Chiocca E. Antonio. , Fehse Boris , Giebel Bernd , Görgens André , Westphal Manfred , Lamszus Katrin
Published: March 2019

Cells release heterogeneous nano‐sized vesicles either as exosomes, being derived from endosomal compartments, or through budding from the plasma membrane as so‐called microvesicles, commonly referred to as extracellular vesicles (EVs). EVs are known for their important roles in mammalian physiology and disease pathogenesis and provide a potential biomarker source in cancer patients. EVs are generally often analysed in bulk using Western blotting or by bead‐based flow‐cytometry or, with limited parameters, through nanoparticle tracking analysis. Due to their small size, single EV analysis is technically highly challenging. Here we demonstrate imaging flow cytometry (IFCM) to be a robust, multiparametric technique that allows analysis of single EVs and the discrimination of distinct EV subpopulations. We used IFCM to analyse the tetraspanin (CD9, CD63, CD81) surface profiles on EVs from human and murine cell cultures as well as plasma samples. The presence of EV subpopulations with specific tetraspanin profiles suggests that EV‐mediated cellular responses are tightly regulated and dependent on cell environment. We further demonstrate that EVs with double positive tetraspanin expression (CD63+/CD81+) are enriched in cancer cell lines and patient plasma samples. In addition, we used IFCM to detect tumour‐specific GFP‐labelled EVs in the blood of mice bearing syngeneic intracerebral gliomas, indicating that this technique allows unprecedented disease modelling. In summary, our study highlights the heterogeneous and adaptable nature of EVs according to their marker profile and demonstrates that IFCM facilitates multiparametric phenotyping of EVs not only in vitro but also in patient plasma at a single EV level, with the potential for future functional studies and clinically relevant applications.

Abbreviation: EDTA = ethylenediamine tetraacetic acid
Linearity of photovoltaic devices: quantitative assessment with N-lamp method
Authors: Müllejans Harald , Salis Elena
Published: March 2019

The short-circuit current output of photovoltaic (PV) reference device is typically used to determine the incident irradiance of natural or simulated sunlight. Normally the PV reference device is calibrated at standard test conditions and other irradiances are calculated based on a proportionality assumption (termed linearity) between short-circuit current output and incident irradiance. Here the linearity of PV devices is newly defined including a quantitative correction for non-linearity (NL) when measuring incident irradiance. Linearity can be determined experimentally by the flux addition principle such as in the two-lamp method. The latter provides information about linearity between two irradiance levels which differ by a factor of two, but no information on linearity inside this interval. Here this concept is extended to the N-lamp method. It is shown that this provides more detailed linearity information with low uncertainty. Measurements were made with an 11-lamp steady-state solar simulator and showed a NL deviation of 2% in the irradiance range from 100 W m−2 to 1100 W m−2 for the PV reference cell tested. The method is easily implemented, provides detailed quantitative linearity assessment at low cost and can be considered a primary method for linearity assessment, as it does not require any reference device.
Critical fields of Nb3Sn prepared for superconducting cavities
Authors: Keckert S , Junginger T , Buck T , Hall D , Kolb P , Kugeler O , Laxdal R , Liepe M , Posen S , Prokscha T , Salman Z , Suter A , Knobloch J
Published: March 2019

Nb3Sn is currently the most promising material other than niobium for future superconducting radiofrequency cavities. Critical fields above 120 mT in pulsed operation and about 80 mT in CW have been achieved in cavity tests. This is large compared to the lower critical field as derived from the London penetration depth, extracted from low field surface impedance measurements. In this paper direct measurements of the London penetration depth from which the lower critical field and the superheating field are derived are presented. The field of first vortex penetration is measured under DC and RF fields. The combined results confirm that Nb3Sn cavities are indeed operated in a metastable state above the lower critical field but are currently limited to a critical field well below the superheating field.
Energy-optimal strokes for multi-link microswimmers: Purcell's loops and Taylor's waves reconciled
Authors: Alouges François , DeSimone Antonio , Giraldi Laetitia , Or Yizhar , Wiezel Oren
Published: March 2019

Micron-scale swimmers move in the realm of negligible inertia, dominated by viscous drag forces. In this paper, we formulate the leading-order dynamics of a slender multi-link (N-link) microswimmer assuming small-amplitude undulations about its straight configuration. The energy-optimal stroke to achieve a given prescribed displacement in a given time period is obtained as the largest eigenvalue solution of a constrained optimal control problem. Remarkably, the optimal stroke is an ellipse lying within a two-dimensional plane in the (N – 1)-dimensional space of joint angles, where N can be arbitrarily large. For large N, the optimal stroke is a traveling wave of bending, modulo edge effects. If the number of shape variables is small, we can consider the same problem when the prescribed displacement in one time period is large, and not attainable with small variations of the joint angles. The fully nonlinear optimal control problem is solved numerically for the cases N = 3 (Purcell’s three-link swimmer) and N = 5 showing that, as the prescribed displacement becomes small, the optimal solutions obtained using the small-amplitude assumption are recovered. We also show that, when the prescribed displacements become large, the picture is different. For N = 3 we recover the non-convex planar loops already known from previous studies. For N = 5 we obtain non-planar loops, raising the question of characterizing the geometry of complex high-dimensional loops.
On-chip integration of single solid-state quantum emitters with a SiO2 photonic platform
Authors: Böhm Florian , Nikolay Niko , Pyrlik Christoph , Schlegel Jan , Thies Andreas , Wicht Andreas , Tränkle Günther , Benson Oliver
Published: March 2019

One important building block for future integrated nanophotonic devices is the scalable on-chip interfacing of single photon emitters and quantum memories with single optical modes. Here we present the deterministic integration of a single solid-state qubit, the nitrogen-vacancy (NV) center, with a photonic platform consisting exclusively of SiO2 grown thermally on a Si substrate. The platform stands out by its ultra-low fluorescence and the ability to produce various passive structures such as high-Q microresonators and mode-size converters. By numerical analysis an optimal structure for the efficient coupling of a dipole emitter to the guided mode could be determined. Experimentally, the integration of a preselected NV emitter was performed with an atomic force microscope and the on-chip excitation of the quantum emitter as well as the coupling of single photons to the guided mode of the integrated structure could be demonstrated. Our approach shows the potential of this platform as a robust nanoscale interface of on-chip photonic structures with solid-state qubits.
Hankel-total positivity of some sequences
Authors: Zhu Bao-Xuan
Published: March 2019

The aim of this paper is to develop analytic techniques to deal with Hankel-total positivity of sequences.

We show two nonlinear operators preserving Stieltjes moment property of sequences. They actually both extend a result of Wang and Zhu that if

(

a
n

)

n
≥
0

(a_n)_{n\geq 0}

is a Stieltjes moment sequence, then so is

(

a

n
+
2

a

n

−

a

n
+
1

2

)

n
≥
0

(a_{n+2}a_{n}-a^2_{n+1})_{n\geq 0}

. Using complete monotonicity of functions, we also prove Stieltjes moment properties of the sequences
<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" alttext="left-parenthesis StartFraction normal upper Gamma left-parenthesis n 0 plus a i plus 1 right-parenthesis Over normal upper Gamma left-parenthesis k 0 plus b i plus 1 right-parenthesis normal upper Gamma left-parenthesis left-parenthesis n 0 minus k 0 right-parenthesis plus left-parenthesis a minus b right-parenthesis i plus 1 right-parenthesis EndFraction product Underscript j equals 0 Overscript m Endscripts StartFraction 1 Over d Subscript j Baseline i plus e Subscript j Baseline EndFraction right-parenthesis Subscript i greater-than-or-equal-to 0">

(

Γ
(

n

0

+
a
i
+
1
)

Γ
(

k

0

+
b
i
+
1
)

Γ
(
(

n
0

−

k
0

)
+
(
a
−
b
)
i
+
1
)

∏

j
=
0

m

1

d
j

i
+

e
j

)

i
≥
0

\left ( \frac {\Gamma (n_{0}+ai+1)}{{\Gamma (k_{0}+bi+1)} {\Gamma ((n_0-k_0)+(a-b)i+1)}}\prod _{j=0}^m\frac {1}{d_ji+e_j}\right )_{i\geq 0}

and
<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" alttext="left-parenthesis sigma-summation Underscript k greater-than-or-equal-to 0 Endscripts StartFraction alpha Subscript k Baseline Over lamda Subscript k Superscript n Baseline EndFraction right-parenthesis Subscript n greater-than-or-equal-to 0">

(

∑

k
≥
0

α
k

λ

k

n

)

n
≥
0

\left (\sum _{k\ge 0}\frac {\alpha _k}{\lambda _{k}^{n}}\right )_{n\geq 0}

. Particularly in a new unified manner our results imply the Stieltjes moment properties of binomial coefficients

(

p
n
+
r
−
1

n

)

\binom {pn+r-1}{n}

and Fuss-Catalan numbers

r

p
n
+
r

(

p
n
+
r

n

)

\frac {r}{pn+r}\binom {pn+r}{n}

proved by Mlotkowski, Penson, and Zyczkowski, and Liu and Pego, respectively, and also extend some results for log-convexity of sequences proved by Chen-Guo-Wang, Su-Wang, Yu, and Wang-Zhu, respectively.
Mitochondrial carrier protein overloading and misfolding induce aggresomes and proteostatic adaptations in the cytosol
Authors: Liu Yaxin , Wang Xiaowen , Coyne Liam P. , Yang Yuan , Qi Yue , Middleton Frank A. , Chen Xin Jie
Published: March 2019

Previous studies in yeast showed that mitochondrial stressors not directly targeting the protein import machinery can cause mitochondrial precursor overaccumulation stress (mPOS) in the cytosol independent of bioenergetics. Here, we demonstrate mPOS and stress responses in human cells. We show that overloading of mitochondrial membrane carrier, but not matrix proteins, is sufficient to induce cytosolic aggresomes and apoptosis. The aggresomes appear to triage unimported mitochondrial proteins. Interestingly, expression of highly unstable mutant variants of the mitochondrial carrier protein, Ant1, also induces aggresomes despite a greater than 20-fold reduction in protein level compared to wild type. Thus, overloading of the protein import machinery, rather than protein accumulation, is critical for aggresome induction. The data suggest that the import of mitochondrial proteins is saturable and that the cytosol is limited in degrading unimported mitochondrial proteins. In addition, we found that EGR1, eEF1a, and ubiquitin C are up-regulated by Ant1 overloading. These proteins are known to promote autophagy, protein targeting to aggresomes, and the processing of protein aggregates, respectively. Finally, we found that overexpression of the misfolded variants of Ant1 induces additional cytosolic responses including proteasomal activation. In summary, our work captured a profound effect of unimported mitochondrial proteins on cytosolic proteostasis and revealed multiple anti-mPOS mechanisms in human cells.
The Difference Between Unfixed and Postfixation Placental Weight
Authors: Tambouret Rosemary , Jeck William R , Roberts Drucilla J
Published: March 2019

Objectives

Reference values for placental weights correlated with gestational age are used in surgical pathology. Most reference values were established for fresh placentas. Some laboratories routinely fix all placentas, bringing into question the accuracy of the reference weight values. We wanted to determine the impact of fixation on placental weight.

Methods

One hundred placentas from uncomplicated pregnancies were weighed in the fresh state, after removal of the cord and membranes. After fixation in formalin for 1 day and 5 days, the placentas were reweighed. The change in weight for each placenta was analyzed by a two-tailed paired t test.

Results

Statistically, a small but significant gain in weight occurred after 24 hours (3.7%, P << .001), and there was no significant change identified in the additional 4 days (P = .51). Nine placentas lost weight with fixation; the weight of four was unchanged.

Conclusions

We consider formalin fixation to add a statistically significant but clinically negligible amount of weight to the placenta.
Ethnicity-Specific Changes in Cardiac Troponin T in Response to Acute Mental Stress and Ethnicity-Specific Cutpoints for the R Wave of the aVL Lead
Authors: Wentzel Annemarie , Malan Leoné , von Känel Roland , Malan Nicolaas T
Published: March 2019

Acute mental stressor–induced cardiac stress responses might contribute to excessive myocardial strain and resultant cardiovascular episode risk. We assessed ethnicity-specific acute cardiac stress (by measuring cardiac troponin T (cTnT) and N-terminal prohormone of brain natriuretic peptide) related to hemodynamic activity. The prospective Sympathetic Activity and Ambulatory Blood Pressure in Africans (SABPA) study was conducted during 2007–2008 in South Africa. In the cross-sectional phase of the SABPA study, 388 black and white participants underwent a 1-minute acute mental stressor, during which blood pressure was continuously measured. Fasting blood samples for cardiac stress markers were obtained before and 10 minutes after stress (% change). Resting 10-lead electrocardiogram measured the R wave of the aVL lead (RaVL). Black participants exhibited greater cardiac stress responses (P < 0.001), diastolic blood pressure, total peripheral resistance, and stroke volume compared with white participants, who displayed decreases in cardiac stress and increases in cardiac output. Prestress and stressor cTnT cutpoints of 4.2 pg/mL predicted 24-hour, daytime, and nighttime diastolic hypertension in black participants (P < 0.001). These cTnT cutpoints were associated with an ethnicity-specific RaVL cutpoint of 0.28 mV (odds ratio = 3.49, 95% confidence interval: 2.18, 5.83; P = 0.021). Acute mental stress elicited an α-adrenergic activation pattern and cardiac stress hyperreactivity only in black participants. Mental stress might increase the black population’s risk for ischemic episodes and heart disease.
Qatar Biobank Cohort Study: Study Design and First Results
Authors: Al Thani Asma , Fthenou Eleni , Paparrodopoulos Spyridon , Al Marri Ajayeb , Shi Zumin , Qafoud Fatima , Afifi Nahla
Published: March 2019

We describe the design, implementation, and results of the Qatar Biobank (QBB) cohort study for the first 10,000 participants. QBB is a prospective, population-based cohort study in Qatar, established in 2012. QBB’s primary goal was to establish a cohort accessible to the local and international scientific community, providing adequate health data and biological samples to enable evidence-based research. The study design is based on an agnostic hypothesis, collecting data using questionnaires, biological samples, imaging data, and -omics. QBB aims to recruit 60,000 participants, men and women, adult (aged ≥18 years) Qataris or long-term residents (≥15 years living in Qatar) and follow up with them every 5 years. Currently, QBB has reached 28% (n = 17,065) of the targeted enrollee population and more than 2 million biological samples. QBB is a multinational cohort including 33 different nationalities, with a relatively young population (mean age, 40.5 years) of persons who are highly educated (50% university-educated) and have high monthly incomes. The 4 main noncommunicable diseases found among the QBB population are dyslipidemia, diabetes, hypertension, and asthma with prevalences of 30.1%, 17.4%, 16.8%, and 9.1%, respectively. The QBB repository can provide data and biological samples sufficient to demonstrate valid associations between genetic and/or environmental exposure and disease development to scientists worldwide.
SArKS: de novo discovery of gene expression regulatory motif sites and domains by suffix array kernel smoothing
Authors: Wylie Dennis C , Hofmann Hans A , Zemelman Boris V
Published: March 2019

Motivation

We set out to develop an algorithm that can mine differential gene expression data to identify candidate cell type-specific DNA regulatory sequences. Differential expression is usually quantified as a continuous score—fold-change, test-statistic, P-value—comparing biological classes. Unlike existing approaches, our de novo strategy, termed SArKS, applies non-parametric kernel smoothing to uncover promoter motif sites that correlate with elevated differential expression scores. SArKS detects motif k-mers by smoothing sequence scores over sequence similarity. A second round of smoothing over spatial proximity reveals multi-motif domains (MMDs). Discovered motif sites can then be merged or extended based on adjacency within MMDs. False positive rates are estimated and controlled by permutation testing.

Results

We applied SArKS to published gene expression data representing distinct neocortical neuron classes in Mus musculus and interneuron developmental states in Homo sapiens. When benchmarked against several existing algorithms using a cross-validation procedure, SArKS identified larger motif sets that formed the basis for regression models with higher correlative power.

Availability and implementation

https://github.com/denniscwylie/sarks.

Supplementary information

Supplementary data are available at Bioinformatics online.