bluuebunny/crossref_metadata_2025 huggingface dataset:
Integrated design method for LCL‐type filter and current controller to improve inverter adaptability to grid impedance
Authors: Zheng Chen , Liu Yajuan , Li Qionglin , Liu Shuming , Zhang Bo , Wang Yi , Mao Mingxuan
Published: August 2019

To characterise the grid‐connected inverter with strong robustness against grid impedance, this study proposes an integrated design approach of LCL‐type filter and controller parameters. In the approach, the inherent relation between LCL‐type filter and controller in regarding to inverter robustness is revealed and utilised to realise the optimised match between LCL‐type‐filter parameters and controller parameters. To facilitate the analysis of stability and robustness, a parameter normalisation scheme is also proposed. With the scheme, relevant normalisation parameters can be designed succinctly according to the required stability and robustness. Additionally, the LCL‐type parameter and controller parameter can be achieved immediately by restoring normalisation parameters. Based on the approach parameter constraints and design guidelines for robust grid‐connected inverter design are also derived in the study to facilitate its application in practice. The proposed inverter design method can guarantee the inverter stability and robustness simultaneously without needing the complicated iterative computations, which cannot be avoided for conventional design methods. Simulation and experimental results are presented to validate the performance and demonstrate the merits of the integrated design method.
Review and analysis of SiC MOSFETs’ ruggedness and reliability
Authors: Wang Jun , Jiang Xi
Published: August 2019

SiC MOSFETs (silicon carbide metal‐oxide semiconductor field‐effect transistors) are replacing Si insulated gate bipolar transistors in many power conversion applications due to their superior performance. However, ruggedness and reliability of SiC MOSFETs are still big concern for their widespread applications in the market, especially in safety‐critical applications. The objective of this study is to provide a comprehensive picture on the ruggedness and reliability of commercial SiC MOSFETs, discover their failure or degradation mechanism, and propose some possible mitigation methods through both literature survey and in‐depth analysis. The ruggedness of SiC MOSFETs discussed here includes short‐circuit (SC) ruggedness, avalanche ruggedness, and their failure mechanism. The reliability issues include gate oxide reliability, degradation under high‐temperature bias stress, repetitive SC stress, avalanche stress, power cycling stress, body diode's surge current stress, and their degradation mechanism. Furthermore, this study discusses methods and solutions to improve their ruggedness and reliability.
Equivalent input disturbance observer‐based ripple‐free deadbeat control for voltage regulation of a DC–DC buck converter
Authors: Yuan Hai‐Bo , Kim Young‐Bae
Published: August 2019

In this research, voltage regulation of a DC–DC buck converter is realised via the ripple‐free deadbeat control (RFDBC) with the equivalent input disturbance observer (EIDO). A small‐signal state‐space model is constructed for the RFDBC design of a converter. Faced with mismatched models, unknown parameter perturbation, and time‐varying voltage source and load demands, augmented disturbance state is constructed and extended state observer is utilised to estimate this augmented model accurately. Based on this model, EIDO is proposed to evaluate the equivalent input disturbance affecting on the input channel. Disturbance compensation is analysed in theory, and the simulation model of the proposed EIDO‐based RFDBC is created to illustrate the control performance in MATLAB/Simulink. Finally, a LabVIEW‐based FPGA experimental rig is set up for the voltage regulation of a DC–DC buck converter. Two other controllers, RFDBC without EIDO and active disturbance rejection control are also designed for performance comparison. The performance comparison result of transient tracking indicates the outstanding characteristics of the proposed controller.
Demonstration of distributed digital array radar experiment system
Authors: Wang Lu , Li Yingjun , An Zhengshuai , Xie Huanhuan
Published: August 2019

The distributed array radar (DAR) increases the aperture size of radar by coherently synthesising distributed sub‐arrays. These sub‐arrays form a long baseline, large array, and are capable of improving the angular resolution and detection range of targets. The DAR brings more freedom in the designing of large physical aperture array radar. This study demonstrates a distributed digital array radar experimental system, which can be used for the DAR principle experiment and performance test. This system combines the advantages of ultra‐wideband antenna and digital array radar, and enables the array aperture to be reconstructed flexibly in both horizontal and vertical. The system can be used to optimise DAR systems for different array size requirements. A description of system design is demonstrated, while the key performance is briefly analysed.
Polar format algorithm of synthetic aperture radar imaging on spiral trajectory
Authors: Li Feng , Yang Wengu , Wang Zhou , Yao Di
Published: August 2019

A novel polar format algorithm is proposed for spiral trajectory. The synthetic aperture radar (SAR) signal model of spiral trajectory platform is firstly established, then the sector‐by‐sector phase compensation method of spiral trajectory SAR is proposed. With the descending of the flight platform, the slant range also decreases, thus the sector‐by‐sector phase compensation is required to correct the quadratic terms of the Range Cell Migration to expand the effective imaging range and eliminate the defocus of the target at the edge of the scene. The 2D‐NUFFT is used to transform the 2D wavenumber domain instead of the traditional nearest interpolation method, which decreases the calculation. Finally, the algorithm is validated by simulation.
Study on the simulation of simultaneous full AT‐POLINSAR
Authors: Zhang Peng , Yan Penghao , Yao Jialun , Zhao Xuan , Zhang Qi , Liu Tao
Published: August 2019

With the maturity of the instantaneous full‐polarisation measurement, the instantaneous full‐polarimetric system is becoming an important development direction of the polarimetric synthetic aperture radar (POLSAR); however, as an important research branch of the synthetic aperture radar (SAR), the along‐track interferometry (ATI) technology for the ground moving target indication (GMTI) is still largely confined to be single polarimetric. In order to facilitate the study of GMTI using a full‐polarimetric along‐track interferometric SAR (AT‐POLINSAR), this study first models the transmitting and receiving signals of AT‐POLINSAR and points out its realisability in the existing technical condition of POLSAR. Then, the 6D vector interferometric model for the full‐polarimetric echoes is established, where the differences of data processing with the single‐polarimetric ATI are analysed. Finally, two simulation methods of the AT‐POLINSAR images are given for the generation of signal‐level and image‐level data, where the results have shown that both the data quality of the interferometric system and its detection performance for moving targets can be improved by the introduction of full polarisation.
Fast signal reconstruction and recognition algorithm based on cascading redundant dictionary and block sparsity for compressed sensing radar receiver
Authors: Zhang Chaozhu , Qiu Peipei , Xu Hongyi
Published: August 2019

The compressed sensing (CS) radar receiver based on the theory of CS has a great advantage in receiving wide‐band signal and can receive high‐frequency radar signal at a sampling rate far lower than the traditional receiver. However, in order to obtain the information of the target signal, the parameters of the reconstructed signal still need to be measured by conventional methods. In order to make full use of the compressed sampling and the characteristics of radar signals, this study proposed a cascading dictionary matching pursuit algorithm based on block‐sparsity (BS‐CDMP) to achieve fast identification and reconstruction of received signals. First, a signal‐level redundant dictionary is constructed for quickly identifying the signal in which the authors are interested in. Then, they study the feasibility of cascading the signal‐level redundant dictionary and the DFT basis as a whole sparsity dictionary. Finally, the block sparsity is introduced for the selection of different parts of the dictionary during greedy iteration. Experimental results show that their proposed algorithm has considerable and universal reconfiguration performance and can directly perform fast reconstruction and recognition of the target signal.
Microstrip antenna with L‐shaped slots for circularly polarised satellite applications
Authors: Abo El‐Hassan May , Hussein Khalid Fawzy A. , Awadalla Kamal H.
Published: August 2019

A novel compact design of a circularly polarised corner‐slotted microstrip antenna for satellite and synthetic aperture radar (SAR) applications is presented. A single‐feed is used to excite a single‐square patch with two L‐shaped slots added at the upper right corner and at the opposite lower left corner (or at the other two corners) to achieve circular polarisation (CP) radiation. The proposed antenna has a simple shape, straightforward fabrication, and low cost. The impedance bandwidth (10 dB return loss) is ∼600 MHz at 8.1 GHz. An axial ratio bandwidth of 170 MHz is realised. The importance of the axial ratio 3 dB bandwidth is emphasised. In addition, an analysis for the direction of rotation of the CP is given. The experimental results have a reasonable agreement with the simulation.
Synthetic observations of dust emission and polarisation of Galactic cold clumps
Authors: Juvela Mika , Padoan Paolo , Ristorcelli Isabelle , Pelkonen Veli-Matti
Published: August 2019

Context. The Planck Catalogue of Galactic Cold Clumps (PGCC) contains over 13 000 sources that are detected based on their cold dust signature. They are believed to consist of a mixture of quiescent, pre-stellar, and already star-forming objects within molecular clouds.

Aims. We extracted PGCC-type objects from cloud simulations and examined their physical and polarisation properties. The comparison with the PGCC catalogue helps to characterise the properties of this large sample of Galactic objects and, conversely, provides valuable tests for numerical simulations of large volumes of the interstellar medium and the evolution towards pre-stellar cores.

Methods. We used several magnetohydrodynamical simulation snapshots to define the density field of our model clouds. Sub-millimetre images of the surface brightness and polarised signal were obtained with radiative transfer calculations. We examined the statistics of synthetic cold clump catalogues extracted with methods similar to the PGCC. We also examined the variations of the polarisation fraction p in the clumps.

Results. The clump sizes, aspect ratios, and temperatures in the synthetic catalogue are similar to the PGCC. The fluxes and column densities of synthetic clumps are smaller by a factor of a few. Rather than with an increased dust opacity, this could be explained by increasing the average column density of the model by a factor of two to three, close to N(H2) = 1022 cm−2. When the line of sight is parallel to the mean magnetic field, the polarisation fraction tends to increase towards the clump centres, which is contrary to observations. When the field is perpendicular, the polarisation fraction tends to decrease towards the clumps, but the drop in p is small (e.g. from p ~8% to p ~7%).

Conclusions. Magnetic field geometry reduces the polarisation fraction in the simulated clumps by only Δp ~1% on average. The larger drop seen towards the actual PGCC clumps therefore suggests some loss of grain alignment in the dense medium, such as predicted by the radiative torque mechanism. The statistical study is not able to quantify dust opacity changes at the scale of the PGCC clumps.
Dominant modes in hydromagnetic stability of channel flow with porous walls
Authors: Lamine M. , Hifdi A.
Published: August 2019

A linear stability analysis of a plane channel flow with porous walls under a uniform cross-flow and an external transverse magnetic field is explored. The physical problem is governed by a system of combined equations of the hydrodynamic and those of Maxwell. The perturbed problem of base state leads to a modified classical Orr-Sommerfeld equation which is solved numerically using the Chebyshev spectral collocation method. The combined eﬀects of the cross-flow Reynolds number and the Hartmann number on the dangerous mode of hydromagnetic stability are investigated.The study shows that, the magnetic field tends to suppress the instability occurred by cross-flow. This stabilizing eﬀect becomes perceptible when the magnetic field produces a mode transition from walls mode to that of the center.
Statistical analysis of locomotives traction motors performance
Authors: Gorobchenko Oleksander , Tkachenko Victor
Published: August 2019

In this article the authors quoted results of traction motors speed performance variations statistical analysis and wage wheels bands diameters deviations according to operation data. The authors of this publication offered the method of determining the non-uniformities of current distribution in the power circuit of the locomotive, based on probabilistic approach, and also performed its comparison with classic computation approach. The next statistical performance of the continuous current locomotives traction drive is as follows: mathematical expectation of the motors magnetic flux; mean square deviation of magnetic flux; statistical dispersion and average square deviation of wage wheels bands diameters. With help of the received data it became possible to improve determination of non-uniformities currents deviations on traction motors during loading of the electric locomotives.
Phenylethanoid glycosides from Paraboea martinii protect rat pheochromocytoma (PC12) cells from hydrogen peroxide-induced cell injury
Authors: Gong Xue , Xu Yan , Ren Kai , Bai Xiaorong , Zhang Chunhong , Li Minhui
Published: August 2019

In this study, we isolated eight phenylethanoid glycosides from Paraboea martinii for the first time, and evaluated the mechanism underlying their neuroprotective effects against H2O2-induced injury in PC12 cells. The MTS method was utilized to screen the phenylethanoid glycosides for protective ability. Next, qRT-PCR and western blotting analysis were used to detect the transcription levels of HO-1 and GCLC, which are regulated by Nrf2. The inhibitor ZnPP was used to analyze the involvement of Nrf2 in HO-1 expression. Analyses showed that caleolarioside B, paraboside B, and paraboside II also upregulated the expression of HO-1, but showed no obvious effect on GCLC. Pretreatment with ZnPP significantly reduced the neuroprotective effects. Thus, phenylethanoid glycosides isolated from P. martinii protected PC12 cells from H2O2-induced damage by upregulating HO-1. The results provided evidence that P. martinii might be a potential therapeutic agent for the treatment of neurodegenerative diseases.
Micro Methods for Megafauna: Novel Approaches to Late Quaternary Extinctions and Their Contributions to Faunal Conservation in the Anthropocene
Authors: Swift Jillian A , Bunce Michael , Dortch Joe , Douglass Kristina , Faith J Tyler , Fellows Yates James A , Field Judith , Haberle Simon G , Jacob Eileen , Johnson Chris N , Lindsey Emily , Lorenzen Eline D , Louys Julien , Miller Gifford , Mychajliw Alexis M , Slon Viviane , Villavicencio Natalia A , Waters Michael R , Welker Frido , Wood Rachel , Petraglia Michael , Boivin Nicole , Roberts Patrick
Published: August 2019

Drivers of Late Quaternary megafaunal extinctions are relevant to modern conservation policy in a world of growing human population density, climate change, and faunal decline. Traditional debates tend toward global solutions, blaming either dramatic climate change or dispersals of Homo sapiens to new regions. Inherent limitations to archaeological and paleontological data sets often require reliance on scant, poorly resolved lines of evidence. However, recent developments in scientific technologies allow for more local, context-specific approaches. In the present article, we highlight how developments in five such methodologies (radiocarbon approaches, stable isotope analysis, ancient DNA, ancient proteomics, microscopy) have helped drive detailed analysis of specific megafaunal species, their particular ecological settings, and responses to new competitors or predators, climate change, and other external phenomena. The detailed case studies of faunal community composition, extinction chronologies, and demographic trends enabled by these methods examine megafaunal extinctions at scales appropriate for practical understanding of threats against particular species in their habitats today.
Processing automatic seismic event detections: an iterative sorting algorithm improving earthquake hypocentres using interevent cross-correlation
Authors: Wagner F , Tryggvason A , Roberts R , Gudmundsson Ó
Published: August 2019

We present an iterative classification scheme using interevent cross-correlation to update an existing earthquake catalogue with similar events from a list of automatic seismic event detections. The algorithm automatically produces catalogue quality events, with improved hypocentres and reliable P- and S-arrival time information.

Detected events are classified into four event categories with the purpose of using the top category, with the highest assessed event quality and highest true-to-false ratio, directly for local earthquake tomography without additional manual analysis. The remaining categories have varying proportions of lower quality events, quality being defined primarily by the number of observed phase onsets, and can be viewed as different priority groups for manual inspection to reduce the time spent by a seismic analyst.

A list of 3348 event detections from the geothermally active volcanic region around Hengill, southwest Iceland, produced by our migration and stack detector (Wagner et al. 2017), was processed using a reference catalogue of 1108 manually picked events from the same area.

P- and S-phase onset times were automatically determined for the detected events using correlation time lags with respect to manually picked phase arrivals from different multiple reference events at the same station. A significant improvement of the initial hypocentre estimates was achieved after relocating the detected events using the computed phase onset times. The differential time data set resulting from the correlation was successfully used for a double-difference relocation of the final updated catalogue.

The routine can potentially be implemented in real-time seismic monitoring environments in combination with a variety of seismic event/phase detectors.
Evaluating Efficacy, Safety, and Pharmacokinetics After Switching From Infliximab Originator to Biosimilar CT-P13: Experience From a Large Tertiary Referral Center
Authors: Bronswijk Michiel , Moens Annick , Lenfant Matthias , Tops Sophie , Compernolle Griet , Van Assche Gert , Vermeire Séverine , Gils Ann , Ferrante Marc
Published: August 2019

Background

The use of infliximab biosimilar CT-P13 has increased in patients with inflammatory bowel disease. Nevertheless, doubts about switching from infliximab originator to biosimilar still exist among patients and health care professionals.

Methods

Our tertiary referral center underwent a mandatory switch from infliximab originator to CT-P13 in 2017. We investigated pharmacokinetics, efficacy, and safety of this switch. The primary endpoint was infliximab discontinuation within 6 months of switching. Secondary endpoints included loss of clinical remission, need for treatment optimization, adverse events, evolution of patient-reported outcome, C-reactive protein, infliximab trough levels, and antidrug-antibodies.

Results

A total of 361 patients (54.0% male, 70.0% Crohn’s disease, 55.6% in clinical remission) were enrolled. Infliximab discontinuation within 6 months was observed in 4%. Loss of clinical remission, adverse events, and antidrug-antibodies were identified in only 2.0%, 2.2%, and 1.1% of patients, respectively. C-reactive protein concentrations and infliximab trough levels remained stable. Independent factors associated with remission at 6 months were lower PRO2 at switch (HR 6.024; 95% CI, 4.878–8.000; P < 0.0001) and higher hemoglobin levels (HR 1.383; 95% CI, 1.044–2.299; P = 0.018).

Conclusions

Switching from infliximab originator to CT-P13 was not associated with an increased risk of treatment discontinuation, loss of clinical remission, or adverse events. No significant changes in infliximab trough levels or immunogenicity could be identified.
Nutrient content changes from steaming or soaking timothy-alfalfa hay: effects on feed preferences and acute glycemic response in Standardbred racehorses1
Authors: Owens Tiana G , Barnes Madeline , Gargano Vanessa M , Julien Louise , Mansilla Wilfredo D , Devries Trevor J , Mcbride Brian W , Merkies Katrina , Shoveller Anna K
Published: August 2019

Soaking hay and steaming hay are strategies that are used to reduce respirable dust particles for horses but may result in variable nutrient losses, including nonstructural carbohydrates (NSC) and minerals. Since these losses have not been quantified in Canadian hay yet, the first aim of this study was to identify nutrient losses from first-cut timothy-alfalfa hay grown in southern Ontario, Canada, after soaking for 30 min or steaming for 60 min. It is uncertain whether horses prefer hay when it is dry, soaked, or steamed. To address this, 13 Standardbred racehorses were offered 2 of these hays side by side for 30 min on 6 consecutive occasions until all possible combinations had been offered. Quantity of hay eaten was determined and horses were video recorded during feedings to assess time spent eating and investigating hay. Additionally, consumption of feeds with differing NSC levels has been observed to influence glycemic response in horses; however, this has not been measured in horses consuming steamed hay before and the results from soaked hay studies have been inconclusive. As such, the final aim of this study was to examine acute glycemic response in horses after being fed dry, soaked, and steamed hays. Blood glucose was measured every 30 min from 9 Standardbred racehorses for 6 h following a meal of 0.5% of their body weight of treatment hay on a dry matter basis (DMB). Soaked, but not steamed, hay had lower concentrations of soluble protein, NSC, and potassium in contrast to the same dry hay (P < 0.05). Peak glucose, average blood glucose, total area under the curve, and time to peak did not differ among treatments (P > 0.05). We conclude that acute glycemic response of racehorses was not influenced by soaking or steaming hay. Horses also consumed less soaked hay (DMB) than dry or steamed hay (P < 0.05) and spent less time eating soaked hay than dry or steamed hay (P < 0.05).
Histopathological Changes of Organs (Lungs, Liver, Kidney, and Brain) After Using Two Types of AgiCoat and Acticoat Nanosilver Dressings on Deep Second-Degree Burn in Rat
Authors: Karimi Hamid , Latifi Noor-Ahmad , Mehrjerdi Ali Zare , Jafarnejad Babak , Karimi Ali-Mohammad
Published: August 2019

Prevention of infections is a very important issue in treating the burn wounds. The nanosilver dressings have many promising advantages, but absorption of silver ions and its adverse effects to the body were always a question. The aim of this study was to compare Silver serum levels and acute toxic effects of nanosilver on histopathology of organs (lungs, liver, kidney, spleen, and brain) in two types of AgiCoat and Acticoat (nanosilver) dressings on second-degree deep burn in rat. This is an experimental study conducted in our animal laboratory. We divided 24 Sprague–Dawley male rats weighing 300 to 350 randomly into two groups. After anesthesia, a second deep-degree burn was made over dorsal skins of rats by standard method. For group A, Agicoat and, for group B, Acticoat dressings were used. The dressings were changed every 3 days with AgiCoat and Acticoat, respectively. After 14 days, we got blood samples and tissue samples taken from heart, liver, kidneys, spleen, lungs, and brain and a sample from dorsal skin of the rat for histopathological examinations. The results showed that the levels of serum silver in both groups were significantly higher than the standard level (1.22 part per million (PM); AgiCoat, P = .017; Acticoat, P = .000), but there was no significant difference between the groups (P = .551). Examination of the relationship between the level of serum silver and histopathological changes in liver showed that hepatotoxicity of AgiCoat was higher compared with Acticoat and the difference was significant (P = .002). There were no pathological changes in brain, kidneys, spleen, heart, and lungs. Wound healing was faster in Acticoat group. The nanosilver dressings can cause toxicity in liver but not in kidney, brain, spleen, heart, and lungs. Liver pathology and hepatotoxicity were more prominent in AgiCoat group. Wound healing was faster in Acticoat group.
A Review of the Most Impactful Published Pharmacotherapy-Pertinent Literature of 2017 and 2018 for Clinicians Caring for Patients with Burn or Inhalation Injuries
Authors: Hill David M , Pape Kate O , Zavala Sarah , Boyd Allison N , Gayed Rita M , Reger Melissa , Adams Beatrice , Voycik Meaghan , Carter Kristen E , Quan Asia , Jones Kendrea M , Walroth Todd A
Published: August 2019

Staying current and evaluating literature related to pharmacotherapy in burn or inhalation injury can be difficult as burn care teams are multidisciplinary and pertinent content can be spread across a plethora of journals. The goal of this review is to critically evaluate recently published pharmacotherapy-pertinent literature, assist practitioners staying current, and better identify potential future research targets. Twelve board-certified clinical pharmacists with experience caring for patients with burn and inhalation injuries reviewed and graded scientific literature published in 2017 and 2018. An MeSH-based search revealed 1158 articles related to burns, which were published during the 2-year period. One-hundred fifty one were determined to be potentially related to pharmacotherapy. After exclusions, only 82 (7%) remained for scoring, and the top 10 comprehensively presented. More than half of the reviewed manuscripts were assessed as lacking a significant impact on pharmacotherapy. There is a need for higher impact literature to support pharmacotherapy-pertinent treatment of such complex patients.
Toronto Workshop on Late Recurrence in Estrogen Receptor-Positive Breast Cancer: Part 2: Approaches to Predict and Identify Late Recurrence, Research Directions
Authors: Dowling Ryan J O , Sparano Joseph A , Goodwin Pamela J , Bidard Francois-Clement , Cescon David W , Chandarlapaty Sarat , Deasy Joseph O , Dowsett Mitch , Gray Robert J , Henry N Lynn , Meric-Bernstam Funda , Perlmutter Jane , Sledge George W , Thorat Mangesh A , Bratman Scott V , Carey Lisa A , Chang Martin C , DeMichele Angela , Ennis Marguerite , Jerzak Katarzyna J , Korde Larissa A , Lohmann Ana Elisa , Mamounas Eleftherios P , Parulekar Wendy R , Regan Meredith M , Schramek Daniel , Stambolic Vuk , Whelan Timothy J , Wolff Antonio C , Woodgett Jim R , Kalinsky Kevin , Hayes Daniel F
Published: August 2019

Late disease recurrence (more than 5 years after initial diagnosis) represents a clinical challenge in the treatment and management of estrogen receptor-positive breast cancer (BC). An international workshop was convened in Toronto, Canada, in February 2018 to review the current understanding of late recurrence and to identify critical issues that require future study. The underlying biological causes of late recurrence are complex, with the processes governing cancer cell dormancy, including immunosurveillance, cell proliferation, angiogenesis, and cellular stemness, being integral to disease progression. These critical processes are described herein as well as their role in influencing risk of recurrence. Moreover, observational and interventional clinical trials are proposed, with a focus on methods to identify patients at risk of recurrence and possible strategies to combat this in patients with estrogen receptor-positive BC. Because the problem of late BC recurrence of great importance, recent advances in disease detection and patient monitoring should be incorporated into novel clinical trials to evaluate approaches to enhance patient management. Indeed, future research on these issues is planned and will offer new options for effective late recurrence treatment and prevention strategies.
Simulation Modeling to Extend Clinical Trials of Adjuvant Chemotherapy Guided by a 21-Gene Expression Assay in Early Breast Cancer
Authors: Jayasekera Jinani , Sparano Joseph A , Gray Robert , Isaacs Claudine , Kurian Allison , O’Neill Suzanne , Schechter Clyde B , Mandelblatt Jeanne
Published: August 2019

Purpose

The Trial Assigning Individualized Options for Treatment (TAILORx) found chemotherapy could be omitted in many women with hormone receptor–positive, HER2-negative, node-negative breast cancer and 21-gene recurrence scores (RS) 11–25, but left unanswered questions. We used simulation modeling to fill these gaps.

Methods

We simulated women eligible for TAILORx using joint distributions of patient and tumor characteristics and RS from TAILORx data; treatment effects by RS from other trials; and competing mortality from the Surveillance, Epidemiology, and End Results program database. The model simulations replicated TAILORx design, and then tested treatment effects on 9-year distant recurrence-free survival (DRFS) in 14 new scenarios: eight subgroups defined by age (≤50 and >50 years) and 21-gene RS (11–25/16–25/16–20/21–25); six different RS cut points among women ages 18–75 years (16–25, 16–20, 21–25, 26–30, 26–100); and 20-year follow-up. Mean hazard ratios SD, and DRFS rates are reported from 1000 simulations.

Results

The simulation results closely replicated TAILORx findings, with 75% of simulated trials showing noninferiority for chemotherapy omission. There was a mean DRFS hazard ratio of 1.79 (0.94) for endocrine vs chemoendocrine therapy among women ages 50 years and younger with RS 16–25; the DFRS rates were 91.6% (0.04) for endocrine and 94.8% (0.01) for chemoendocrine therapy. When treatment was randomly assigned among women ages 18–75 years with RS 26–30, the mean DRFS hazard ratio for endocrine vs chemoendocrine therapy was 1.60 (0.83). The conclusions were unchanged at 20-year follow-up.

Conclusions

Our results confirmed a small benefit in chemotherapy among women aged 50 years and younger with RS 16–25. Simulation modeling is useful to extend clinical trials, indicate how uncertainty might affect results, and power decision tools to support broader practice discussions.
On Parfit’s Wide Dual Person-Affecting Principle
Authors: Masny Michal
Published: August 2019

In the posthumously published ‘Future People, the Non-Identity Problem, and Person-Affecting Principles’ (2017), Derek Parfit presents a novel axiological principle which he calls the Wide Dual Person-Affecting Principle and claims that it does not imply the Repugnant Conclusion. This paper shows that even the best version of Parfit's principle cannot avoid this conclusion. That said, accepting such a principle makes embracing the Repugnant Conclusion more justifiable. This paper further addresses important questions which Parfit left unanswered concerning: the relative importance of individual and collective goodness, comparisons involving unequal outcomes, how to understand individual goodness, and whether incomparability at the level of individual goodness implies incomparability at the level of overall goodness.
Association between the ACE I/D gene polymorphism and progressive renal failure in autosomal dominant polycystic kidney disease: A meta-analysis
Authors: Pabalan Noel , Tharabenjasin Phuntila , Parcharoen Yardnapar , Tasanarong Adis
Published: August 2019

Objective

The angiotensin converting enzyme insertion/deletion (ACE I/D) gene polymorphism is involved in a wide range of clinical outcomes. This makes ACE I/D an important genetic marker. Updating the genetic profile of ACE I/D and raising the evidence for its role in renal disease is therefore needed. Reported associations of ACE I/D with progressive renal failure (PRF) in autosomal dominant polycystic kidney disease (ADPKD) have been inconsistent, prompting a meta-analysis to obtain more precise estimates.

Methods

Multi-database search yielded 18 articles for inclusion in the meta-analysis. Risks (odds ratios [ORs] and 95% confidence intervals) were estimated by comparing the ACE genotypes (heterozygote ID, homozygotes DD and II). Heterogeneous (random-effects) pooled associations were subjected to outlier treatment which yielded fixed-effects outcomes and split the findings into pre- (PRO) and post- (PSO) outlier status. Subgroup analysis was based on ethnicity (Asian/Caucasian) and minor allele frequency (maf). The ≥ 0.50 maf subgroup indicates higher frequency of the variant II genotype over that of the common DD genotype, otherwise, the subgroup is considered < 0.50 maf. Stability of the associative effects was assessed with sensitivity treatment. Temporal trend of association was examined with cumulative meta-analysis.

Results

In the PSO analysis, overall effects were null (ORs 0.99-1.02) but not in the subgroups (Asian and ≥ 0.50 maf), where in presence of the D allele (DD/ID) and the I allele (II), increased (ORs 1.63-5.62) and reduced (OR 0.22) risks were observed, respectively. Of these pooled effects, the Asian and ≥ 0.50 maf homozygous DD genotypes had high ORs (5.01-5.63) indicating elevated magnitude of effects that were highly significant (Pa < 10−5) and homogeneous (I2 = 0%), in addition to their robustness. In contrast, the Caucasian and < 0.50 maf subgroup effects were: (i) non-heterogeneous (fixed-effects) at the outset, which did not require outlier treatment and (ii) non-significant (ORs 0.91-1.10, Pa = 0.15-0.79). Cumulative meta-analysis revealed increased precision of effects over time.

Conclusions

PRF in ADPKD impacted the Asian and ≥ 0.50 maf subgroups where DD homozygote carriers were up to 6-fold susceptible. The high magnitude of these effects were highly significant, homogeneous and robust indicating strong evidence of association.
The Effects of Metronome Frequency Differentially Affects Gait on a Treadmill and Overground in People with Parkinson’s Disease
Authors: Wygand Madelon , Chawla Guneet , Browner Nina , Lewek Michael D
Published: August 2019

Objective

To determine the effect of different metronome cue frequencies on spatiotemporal gait parameters when walking overground compared to walking on a treadmill in people with Parkinson’s disease

Design

Repeated-measures, within-subject design

Setting

Research laboratory

Participants

Twenty-one people with Parkinson’s disease (Hoehn & Yahr stage 1-3)

Interventions

Participants walked overground and on a treadmill with and without metronome cues of 85%, 100%, and 115% of their baseline cadence for one minute each.

Main Outcome Measures

Gait speed, step length, and cadence

Results

An interaction effect between cue frequency and walking environment revealed that participants took longer steps during the 85% condition on the treadmill only. When walking overground, metronome cues of 85% and 115% of baseline cadence yielded decreases and increases, respectively, in both cadence and gait speed with no concomitant change in step length.

Conclusions

These data suggest that people with PD are able to alter spatiotemporal gait parameters immediately when provided the appropriate metronome cue and walking environment. We propose to target shortened step lengths by stepping to the beat of slow frequency auditory cues while walking on a treadmill, whereas the use of fast frequency cues during overground walking can facilitate faster walking speeds.
Increasing Heroin, Cocaine, and Buprenorphine Arrests Reported to the Maine Diversion Alert Program
Authors: Simpson Kevin J , Moran Matthew T , McCall Kenneth L , Herbert John , Foster Michelle , Simoyan Olapeju M , Shah Dipam T , Desrosiers Clare , Nichols Stephanie D , Piper Brian J
Published: August 2019

Background

The opioid overdose crisis is especially pronounced in Maine. The Diversion Alert Program (DAP) was developed to combat illicit drug use and prescription drug diversion by facilitating communication between law enforcement and healthcare providers with the goal of limiting drug-related harms and criminal behaviors. Our objectives in this report were to analyze 2014-2017 DAP for: 1) trends in drug arrests and, 2) differences in arrests by offense, demographics (sex and age) and by region.

Methods

Drug charges (N = 8,193, 31.3% female, age = 33.1 ± 9.9) reported to the DAP were examined by year, demographics, and location.

Results

The most common substances of the 10,064 unique arrests reported were heroin (N = 2,203, 21.9%), crack/cocaine (N = 945, 16.8%), buprenorphine (N = 812, 8.1%), and oxycodone (N = 747, 7.4%). While the overall number of arrests reported to the DAP declined in 2017, the proportion of arrests involving opioids (heroin, buprenorphine, or fentanyl) and stimulants (cocaine/crack cocaine, or methamphetamine), increased (p < .05). Women had significantly increased involvement in arrests involving sedatives and miscellaneous pharmaceuticals (e.g. gabapentin) while men had an elevation in stimulant arrests. Heroin accounted for a lower percentage of arrests among individuals age > 60 (6.6%) relative to young-adults (18-29, 22.3%, p < .0001). Older-adults had significantly more arrests than younger-adults for oxycodone, hydrocodone, and marijuana.

Conclusion

Heroin had the most arrests from 2014-2017. Buprenorphine, fentanyl and crack/cocaine arrests increased appreciably suggesting that improved treatment is needed to prevent further nonmedical use and overdoses. The Diversion Alert Program provided a unique data source for research, a harm-reduction tool for health care providers, and an informational resource for law enforcement.
Pyntheon: A Functional Analysis Framework for Protein Modifications and Mutations of 83 Model Organisms
Authors: Arslan Ahmed
Published: August 2019

Motivation

Posttranslational modifications (PTMs) modulate proteins activity depending on the dynamics of cellular conditions, in the highly regulated processes that control the reversible nature of these modifications and a cellular state. Due to the unique importance of PTMs, a number of resources are available to analyze the protein modification data for different organisms. These databases are quite informative on a limited number of popular organisms, mostly human and yeast. However there has not been a single database to date that makes it possible to analyze the modified protein residue data for up to 83 model organisms. Moreover, there are limited resources that rely on both protein mutations and modifications in evaluating a phenotype.

Results

I am presenting a comprehensive python toolPyntheonthat enables users to analyze protein modifications and mutations data. This resource can be used in different ways to know: (i) if the proteins of interest have modifications and (ii) if the modified residues overlap with mutated sites. Additional functions include, analyzing if a PTM-site is present in a functional protein region, like domain and structural regions. In summary, Pyntheon makes it possible for a larger community of researchers to evaluate their curated proteomics data and interpret the impact of mutations on phenotypes.

Conclusion

Pyntheon has multifold functions that can help analyzing the protein mutations impact on the modified residues for a large number of popular model organisms.

Code-Availability

https://github.com/AhmedArslan/pyntheon

Contact

aarslan@stanford.edu
In situ Fucosylation for Modulating Wnt Signaling in Live Cells
Authors: Hong Senlian , Feng Lei , Jiang Hao , Hou Xiaomeng , Guo Peng , Marlow Florence L. , Stanley Pamela , Wu Peng
Published: August 2019

Wnt/β-catenin signaling, also known as canonical Wnt signaling, regulates critical, context-dependent transcription in numerous (patho) physiological events. Amongst the well-documented mechanisms of canonical Wnt signaling, modification of N-glycans by L-fucose (Fuc) is the newest and the least understood. Using a combination of Chinese Hamster Ovary (CHO) cell mutants with different fucosylation levels andin situcell-surface Fuc editing (ISF), we report that α(1-3)-fucosylation of N-acetylglucosamine in the LacNAc (Galβ(1-4)-GlcNAc) sequences of complex N-glycans modulates Wnt signaling by regulating the endocytosis of low density lipoprotein receptor-related protein 6 (LRP6). Pulse-chase experiments reveal that increasing N-glycan LacNAc fucosylation elevates endocytosis of lipid-raft-localized LRP6, leading to the suppression of Wnt-β-catenin signaling. Inhibiting endocytosis by inhibiting dynamin 1, a GTPase responsible for endocytosis in eukaryotic cells, partially rescues Wnt signaling. Remarkably, inhibition of Wnt signaling by N-glycan LacNAc fucosylation is fully rescued by the addition of free Fuc to the medium, suggesting that endocytosis of N-glycan fucosylated LRP6 may be mediated by a receptor that recognizes the bound α(1-3)-Fuc. This work provides the first evidence thatin situcell-surface fucosylation can be exploited to regulate a specific signaling pathway via endocytosis, revealing a novel regulatory mechanism linking glycosylation of a cell surface receptor with its intracellular signaling.
Histone ChIP-Seq identifies differential enhancer usage during chondrogenesis as critical for defining cell-type specificity
Authors: Cheung Kathleen , Barter Matthew J. , Falk Julia , Proctor Carole , Reynard Louise N. , Young David A.
Published: August 2019

Epigenetic mechanisms are known to regulate gene expression during chondrogenesis. In this study, we have characterised the epigenome during in vitro differentiation of human mesenchymal stem cells (hMSCs) into chondrocytes. Chromatin immunoprecipitation followed by next-generation sequencing (ChIP-seq) was used to assess a range of N-terminal post-transcriptional modifications (marks) to histone H3 lysines (H3K4me3, H3K4me1, H3K27ac, H3K27me3 and H3K36me3) in both hMSCs and differentiated chondrocytes. Chromatin states were characterised using histone ChIP-seq and cis-regulatory elements were identified in chondrocytes. Chondrocyte enhancers were associated with chondrogenesis related gene ontology (GO) terms. In silico analysis and integration of DNA methylation data with chondrogenesis chromatin states revealed that enhancers marked by histone marks H3K4me1 and H3K27ac were de-methylated during in vitro chondrogenesis. Similarity analysis between hMSC and chondrocyte chromatin states defined in this study with epigenomes of cell-types defined by the Roadmap Epigenomics project revealed that enhancers are more distinct between cell-types compared to other chromatin states. Motif analysis revealed that the transcription factor SOX9 is enriched in chondrocyte enhancers. Luciferase reporter assays confirmed that chondrocyte enhancers characterised in this study exhibited enhancer activity which may be modulated by inducing DNA methylation and SOX9 overexpression. Altogether, these integrated data illustrate the cross-talk between different epigenetic mechanisms during chondrocyte differentiation.

Human mesenchymal stem cells are able to differentiate into chondrocytes, the cell type found in cartilage, making them an accessible system to study gene regulation during this process. Epigenetic mechanisms such as histone modifications and DNA methylation together with transcription factor binding play a role in activating and repressing gene expression. In this study, we investigated the genome-wide histone modification changes during chondrocyte differentiation. Integration of this data with DNA methylation and SOX9 transcription factor ChIP-seq revealed epigenetic changes at gene enhancer elements. Regions of the genome that transition from non-enhancers to enhancers in chondrocytes are enriched for SOX9 transcription factor binding sites. Luciferase reporter assays revealed that enhancer activity may be modulated by manipulating DNA methylation and SOX9 expression. This study has defined important regulatory elements in chondrocytes which could serve as targets for future mechanistic studies.
Prioritizing persistent microbiome members in the common bean rhizosphere: an integrated analysis of space, time, and plant genotype
Authors: Stopnisek Nejc , Shade Ashley
Published: August 2019

The full potential of managing microbial communities to support plant health is yet-unrealized, in part because it remains difficult to ascertain which members are most important for the plant. However, microbes that consistently associate with a plant species across varied field conditions and over plant development likely engage with the host or host environment. Here, we applied abundance-occupancy concepts from macroecology to quantify the core membership of bacterial/archaeal and fungal communities in the rhizosphere of the common bean (Phaseolus vulgaris). Our study investigated the microbiome membership that persisted over multiple dimensions important for plant agriculture, including major growing regions, plant development, annual plantings, and divergent genotypes, and also included re-analysis of public data. We found 48 core bacterial taxa that were consistently detected in all samples, inclusive of all datasets and dimensions. This suggests reliable enrichment of these taxa to the plant environment and time-independence of their association with the plant. More generally, this work provides a robust approach for systematically prioritizing core microbiome memberships in any host or system.
3D mapping of host-parasite-microbiome interactions reveals metabolic determinants of tissue tropism and disease tolerance in Chagas disease
Authors: Hossain Ekram , Khanam Sharmily , Wu Chaoyi , Lostracco-Johnson Sharon , Thomas Diane , Katemauswa Mitchelle , Gosmanov Camil , Li Danyang , Woelfel-Monsivais Christine , Sankaranarayanan Krithivasan , McCall Laura-Isobel
Published: August 2019

Chagas disease (CD) is a parasitic infection caused by Trypanosoma cruzi protozoa. Over 8 million people worldwide are T. cruzi-positive, 20-30% of which will develop cardiomyopathy, megaoesophagus and/or megacolon. The mechanisms leading to gastrointestinal (GI) symptom development are however poorly understood. To address this issue, we systematically characterized the spatial impact of experimental T. cruzi infection on the microbiome and metabolome across the GI tract. The largest microbiota perturbations were observed in the proximal large intestine in both acute and chronic disease, with chronic-stage effects also observed in the cecum. Strikingly, metabolomic impact of acute-to-chronic stage transition differed depending on the organ, with persistent large-scale effects of infection primarily in the oesophagus and large intestine, providing a potential mechanism for GI pathology tropism in CD. Infection particularly affected acylcarnitine and lipid metabolism. Building on these observations, treatment of infected mice with carnitine-supplemented drinking water prevented acute-stage mortality with no changes in parasite burden. Overall, these results identified a new mechanism of disease tolerance in CD, with potential for the development of new therapeutic regimens. More broadly, these results highlight the potential of spatially-resolved metabolomic approaches to provide insight into disease pathogenesis, with translational applications for infectious disease drug development.