bluuebunny/crossref_metadata_2025 huggingface dataset:
Reversible Mitochondrial Fragmentation in iPSC-Derived Cardiomyocytes from Children with DCMA, a Mitochondrial Cardiomyopathy
Authors: Rohani Leili , Machiraju Pranav , Sabouny Rasha , Meng Guoliang , Liu Shiying , Zhao Tian , Iqbal Fatima , Ravandi Amir , Wu Joseph C. , Khan Aneal , Shutt Timothy , Rancourt Derrick , Greenway Steven C.
Published: August 2019

Background

The dilated cardiomyopathy with ataxia syndrome (DCMA) is an understudied autosomal recessive disease caused by loss-of-function mutations in the poorly characterized gene DNAJC19. Clinically, DCMA is commonly associated with heart failure and early death in affected children through an unknown mechanism. DCMA has been linked to Barth syndrome, a rare but well-studied disorder caused by deficient maturation of cardiolipin (CL), a key mitochondrial membrane phospholipid.

Methods

Peripheral blood mononuclear cells from two children with DCMA and severe cardiac dysfunction were reprogrammed into induced pluripotent stem cells (iPSCs). Patient and control iPSCs were differentiated into beating cardiomyocytes (iPSC-CMs) using a metabolic selection strategy and mitochondrial structure and CL content before and after incubation with the mitochondrially-targeted peptide SS-31 were quantified.

Results

Patient iPSCs carry the causative DNAJC19 mutation (rs137854888) found in the Hutterite population and the iPSC-CMs demonstrated highly fragmented and abnormally-shaped mitochondria associated with an imbalanced isoform ratio of the mitochondrial protein OPA1, an important regulator of mitochondrial fusion. These abnormalities were reversible by incubation with SS-31 for 24 hours. Differentiation of iPSCs into iPSC-CMs increased the number of CL species observed but consistent, significant differences in CL content were not seen between patients and control.

Conclusions

We describe a unique and novel cellular model that provides insight into the mitochondrial abnormalities present in DCMA and identifies SS-31 as a potential therapeutic for this devastating disease.
A probabilistic approach to explore signal execution mechanisms with limited experimental data
Authors: Kochen Michael A. , Lopez Carlos F.
Published: August 2019

Mathematical models of biochemical reaction networks are central to the study of dynamic cellular processes and hypothesis generation that informs experimentation and validation. Unfortunately, model parameters are often not available and sparse experimental data leads to challenges in model calibration and parameter estimation. This can in turn lead to unreliable mechanistic interpretations of experimental data and the generation of poorly conceived hypotheses for experimental validation. To address this challenge, we evaluate whether a Bayesian-inspired probability-based approach, that incorporates available information regarding reaction network topology and parameters, can be used to qualitatively explore hypothetical biochemical network execution mechanisms in the context of limited available data. We test our approach on a model of extrinsic apoptosis execution to identify preferred signal execution modes across varying conditions. Apoptosis signal processing can take place either through a mitochondria independent (Type I) mode or a mitochondria dependent (Type II) mode. We first show that in silico knockouts, represented by model subnetworks, successfully identify the most likely execution mode for specific concentrations of key molecular regulators. We then show that changes in molecular regulator concentrations alter the overall reaction flux through the network by shifting the primary route of signal flow between the direct caspase and mitochondrial pathways. Our work thus demonstrates that probabilistic approaches can be used to explore the qualitative dynamic behavior of model biochemical systems even with missing or sparse data.
A single cell atlas of the developingDrosophilaovary identifies follicle stem cell progenitors
Authors: Slaidina Maija , Banisch Torsten U. , Gupta Selena , Lehmann Ruth
Published: August 2019

Addressing the complexity of organogenesis at a system-wide level requires a complete understanding of adult cell types, their origin and precursor relationships. TheDrosophilaovary has been a model to study how coordinated stem cell units, germline and somatic follicle stem cells, maintain and renew an organ. However, lack of cell-type specific tools have limited our ability to study the origin of individual cell types and stem cell units. Here, we use a single cell RNA sequencing approach to uncover all known cell types of the developing ovary, reveal transcriptional signatures, and identify cell type specific markers for lineage tracing. Our study identifies a novel cell type corresponding to the elusive follicle stem cell precursors and predicts sub-types of known cell types. Altogether, we reveal a previously unanticipated complexity of the developing ovary, and provide a comprehensive resource for the systematic analysis of ovary morphogenesis.
Individualized ctDNA Fingerprints to Monitor Treatment Response and Recurrence in Multiple Cancer Types
Authors: Li Jiaping , Jiang Wei , Wei Jinwang , Zhang Jianwei , Cai Linbo , Luo Minjie , Wang Zhan , Sun Wending , Wang Chen , Dai Chun , Wang Guan , Xu Qiang , Deng Yanhong
Published: August 2019

Circulating tumor DNA (ctDNA) panels hold high promise of accurately predicting the therapeutic response of tumors while being minimally invasive and cost-efficient. However, their use has been limited to a small number of tumor types and patients. Here, we developed individualized ctDNA fingerprints suitable for most patients with multiple cancer types. The panels were designed based on individual whole-exome sequencing data in 521 Chinese patients and targeting high clonal population clusters of somatic mutations. Together, these patients represent 12 types of cancers and seven different treatments. The customized ctDNA panels have a median somatic mutation number of 19, most of which are patient-specific rather than cancer hotspot mutations; 66.8% of the patients were ctDNA-positive. We further evaluated the ctDNA content fraction (CCF) of the mutations, and analyzed the association between the change of ctDNA concentration and therapeutic response. We followed up 106 patients for clinical evaluation, demonstrating a significant correlation of changes in ctDNA with clinical outcomes, with a consistency rate of 93.4%. In particular, the median CCF increased by 204.6% in patients with progressive disease, decreased by 82.5% in patients with remission, and was relatively stable in patients with stable disease. Overall, 85% of the patients with a ctDNA-positive status experienced metastasis or relapse long before imaging detection, except for two patients who developed recurrence and metastasis almost simultaneously. The average lead time between the first ctDNA-positive finding and radiological diagnosis was 76 days in three patients that changed from a ctDNA-negative to -positive status. Our individualized ctDNA analysis can effectively monitor the treatment response, metastasis, and recurrence in multiple cancer types in patients with multiple treatment options, therefore offering great clinical applicability for improving personalized treatment in cancer.

One Sentence Summary

ctDNA fingerprint panels were customized to predict the treatment response for multiple cancer types from individual whole-exome sequencing data.
Comparing the utility of in vivo transposon mutagenesis approaches in yeast species to infer gene essentiality
Authors: Levitan Anton , Gale Andrew N. , Dallon Emma K. , Kozan Darby W. , Cunningham Kyle W. , Sharan Roded , Berman Judith
Published: August 2019

In vivo transposon mutagenesis, coupled with deep sequencing, enables large-scale genome-wide mutant screens for genes essential in different growth conditions. We analyzed six large-scale studies performed on haploid strains of three yeast species (Saccharomyces cerevisiae, Schizosaccaromyces pombe, and Candida albicans), each mutagenized with two of three different heterologous transposons (AcDs, Hermes, and PiggyBac). Using a machine-learning approach, we evaluated the ability of the data to predict gene essentiality. Important data features included sufficient numbers and distribution of independent insertion events. All transposons showed some bias in insertion site preference because of jackpot events, and preferences for specific insertion sequences and short-distance vs long-distance insertions. For PiggyBac, a stringent target sequence limited the ability to predict essentiality in genes with few or no target sequences. The machine learning approach also robustly predicted gene function in less well-studied species by leveraging cross-species orthologs. Finally, comparisons of isogenic diploid versus haploid S. cerevisiae isolates identified several genes that are haplo-insufficient, while most essential genes, as expected, were recessive. We provide recommendations for the choice of transposons and the inference of gene essentiality in genome-wide studies of eukaryotic haploid microbes such as yeasts, including species that have been less amenable to classical genetic studies.
Null results from a dimensional study of error-related negativity (ERN) and self-reported psychiatric symptoms
Authors: Seow T. X.F. , Benoit E. , Dempsey C. , Jennings M. , Maxwell A. , McDonough M. , Gillan C. M.
Published: August 2019

Alterations in error processing are implicated in a range of DSM-defined psychiatric disorders. For instance, obsessive-compulsive disorder (OCD) and generalised anxiety disorder show enhanced electrophysiological responses to errors – i.e. error-related negativity (ERN) – while others like schizophrenia have an attenuated ERN. However, as diagnostic categories in psychiatry are heterogeneous and also highly intercorrelated, the precise mapping of ERN enhancements and impairments is unclear. To address this, we recorded electroencephalograms (EEG) from 196 participants who performed the Flanker task and collected scores on 9 questionnaires assessing psychiatric symptoms to test if a dimensional framework could reveal specific transdiagnostic clinical manifestations of error processing dysfunctions. Contrary to our hypothesis, we found no association between ERN amplitude and symptom severity of OCD, trait anxiety, depression, social anxiety, impulsivity, eating disorders, alcohol addiction, schizotypy or apathy. A transdiagnostic approach did nothing to improve signal; there was no association between three transdiagnostic dimensions (anxious-depression, compulsive behaviour and intrusive thought and social withdrawal) and ERN magnitude. In these same individuals, we replicated a previously published transdiagnostic association between goal-directed learning and compulsive behaviour and intrusive thought. Associations between the ERN and psychopathology might be smaller than previously assumed and/or dependent on a greater level of symptom severity than other transdiagnostic cognitive biomarkers.
Cellular metabolic activity marker via selective turn-ON detection of serum albumin using an NBD-based fluoroprobe
Authors: Dutta Tanoy , Pal Kaushik , Koner Apurba Lal
Published: August 2019

A nitrobenzoxadiazole-based fluoroprobe (NBD-Bu) is designed to probe cellular metabolic activity in cancer and normal cells. NBD-Bu shows a significant fluorescence enhancement upon selective binding to serum albumin. The site specificity of NBD-Bu has been explored through a competitive displacement assay in the presence of site-specific markers such as warfarin and ibuprofen. Subsequently, high-resolution fluorescence microscopy results consolidated the potential of NBD-Bu for cellular imaging and detection of abnormal cellular metabolic activity.
BayICE: A hierarchical Bayesian deconvolution model with stochastic search variable selection
Authors: Tai An-Shun , Tseng George C. , Hsieh Wen-Ping
Published: August 2019

Gene expression deconvolution is a powerful tool for exploring the microenvironment of complex tissues comprised of multiple cell groups using transcriptomic data. Characterizing cell activities for a particular condition has been regarded as a primary mission against diseases. For example, cancer immunology aims to clarify the role of the immune system in the progression and development of cancer through analyzing the immune cell components of tumors. To that end, many deconvolution methods have been proposed for inferring cell subpopulations within tissues. Nevertheless, two problems limit the practicality of current approaches. First, all approaches use external purified data to preselect cell type-specific genes that contribute to deconvolution. However, some types of cells cannot be found in purified profiles and the genes specifically over- or under-expressed in them cannot be identified. This is particularly a problem in cancer studies. Hence, a preselection strategy that is independent from deconvolution is inappropriate. The second problem is that existing approaches do not recover the expression profiles of unknown cells present in bulk tissues, which results in biased estimation of unknown cell proportions. Furthermore, it causes the shift-invariant property of deconvolution to fail, which then affects the estimation performance. To address these two problems, we propose a novel deconvolution approach, BayICE, which employs hierarchical Bayesian modeling with stochastic search variable selection. We develop a comprehensive Markov chain Monte Carlo procedure through Gibbs sampling to estimate cell proportions, gene expression profiles, and signature genes. Simulation and validation studies illustrate that BayICE outperforms existing deconvolution approaches in estimating cell proportions. Subsequently, we demonstrate an application of BayICE in the RNA sequencing of patients with non-small cell lung cancer. The model is implemented in the R package “BayICE” and the algorithm is available for download.
Distinct microbial communities alter litter decomposition rates in a fertilized coastal plain wetland
Authors: Koceja Megan E. , Bledsoe Regina B. , Goodwillie Carol , Peralta Ariane L.
Published: August 2019

Abstract

Human activities have led to increased deposition of nitrogen (N) and phosphorus (P) into soils. Nutrient enrichment of soils is known to increase plant biomass and rates of microbial litter decomposition. However, interacting effects of hydrologic position and associated changes to soil moisture can constrain microbial activity and lead to unexpected nutrient feedbacks on microbial community structure-function relationships. Examining how feedbacks of nutrient enrichment on decomposition rates is essential for predicting microbial contributions to carbon (C) cycling as atmospheric deposition of nutrients persists. This study explores how long-term nutrient addition and contrasting litter chemical quality influence soil bacterial community structure and function. We hypothesize that long-term nutrient enrichment of low fertility soils alters bacterial community structure and leads to higher rates of litter decomposition with decreasing C:N ratio of litter; but low nutrient and dry conditions limit constrain microbial decomposition of high C:N ratio litter. We leverage a long-term fertilization experiment to test how nutrient enrichment and hydrologic manipulation (due to ditches) affects decomposition and soil bacterial community structure in a nutrient poor coastal plain wetland. We conducted a litter bag experiment and characterized litter-associated and bulk soil microbiomes using 16S rRNA bacterial sequencing and quantified litter mass losses and soil physicochemical properties. Results revealed that distinct bacterial communities were involved in decomposing higher C:N ratio litter more quickly in fertilized compared to unfertilized especially under drier soil conditions, while decomposition rates of green tea litter (lower C:N ratio) were similar between fertilized and unfertilized plots. Bacterial community structure in part explained litter decomposition rates, and long-term fertilization and drier hydrologic status affected bacterial diversity and increased decomposition rates. However, community composition associated with high C:N litter was similar in wetter plots with available nitrate detected, regardless of fertilization treatment. This study provides insight into long-term fertilization effects on soil bacterial diversity and composition, decomposition, and the increased potential for soil C loss as nutrient enrichment and hydrology interact to affect historically low nutrient ecosystems.
X-ray dynamical diffraction analogues of the integer and fractional Talbot effects
Authors: Balyan Minas K.
Published: August 2019

The X-ray integer and fractional Talbot effect is studied under two-wave dynamical diffraction conditions in a perfect crystal, for the symmetrical Laue case of diffraction. The fractional dynamical diffraction Talbot effect is studied for the first time. A theory of the dynamical diffraction integer and fractional Talbot effect is given, introducing the dynamical diffraction comb function. An expression for the dynamical diffraction polarization-sensitive Talbot distance is established. At the rational multiple depths of the Talbot depth the wavefield amplitude for each dispersion branch is a coherent sum of the initial distributions, shifted by rational multiples of the object period and having its own phases. The simulated dynamical diffraction Talbot carpet for the Ronchi grating is presented.
The effects of personality, culture and store stimuli on impulsive buying behavior
Authors: Miao Miao , Jalees Tariq , Qabool Sahar , Zaman Syed Imran
Published: August 2019

Purpose

The purpose of this paper is to examine the relationship between personality factors (i.e. neuroticism, agreeableness, extroversion, conscientiousness and openness), cultural factors (individualism and collectivism) and store stimuli (window display and sales promotion) on impulsive buying behavior.

Design/methodology/approach

The sample size for the study was 350 with a response rate of 96 percent. The questionnaire was adapted from the established scale and measures. SmartPLS was used for statistical analysis. After reliability and validity analysis, the structural model was tested, and it fitted very well.

Findings

Of the nine hypotheses, five were accepted, and the other four were rejected. The results suggest that neuroticism, openness, individualism, collectivism and sales promotion significantly affect impulsive buying behavior. Marketers can use these results in developing appropriate marketing strategies.

Research limitations/implications

Implications for managers were drawn from the results. In this study, only two cultural factors were considered. Future studies could use all the cultural factors in their model. Additionally, the developed model can be extended for comparative studies.

Originality/value

Impulsive buying behavior, on the one hand, is problematic for consumers, but, on the other hand, is used as a tool by retailers for increasing sales. Comparatively, this study examined the effects of personality factors, cultural factors and store stimuli on impulsive buying behavior. These three factors have rarely been used together in one study.
Symbiotic care between residents in service-integrated housing
Authors: Meyer Desneige , Martin Wanda , Funk Laura M.
Published: August 2019

Purpose

Sustainable solutions for meeting the physical, emotional and social health care needs of individuals may be realized by shifting the care landscape; for instance, through innovative models of service-integrated housing (SIH). By diversifying populations in these settings, care recipients can choose to engage their skills and abilities toward assisting co-residents, and vice versa as a form of symbiosis. The purpose of this paper is to define attributes of the concept and practice of symbiotic care.

Design/methodology/approach

The authors drew on firsthand field experience and secondary data from a literature review to conduct a conceptual derivation and analysis, using Walker and Avant’s methodology. The term symbiotic mutualism was derived from the field of biology as an analogy for care exchanged between non-peer co-residents. Attributes, antecedents and consequences of symbiotic care were identified and illustrated using model, borderline and contrary case descriptions.

Findings

Four defining attributes of symbiotic care were identified: first, cohabitation: care recipients live closely together in SIH settings. Second, non-peer: co-residents have distinct, complementary needs and abilities. Third, mutualism: co-residents experience mutually significant benefits as a result of the activities of their co-residents. Fourth, agency-sponsored: the professional SIH agency or organization attends to unmet resident needs.

Research limitations/implications

Symbiotic care is a relatively rare phenomenon for which little research exists. This analysis provides a starting point for empirical research, policy and program development and critical evaluation.

Originality/value

This paper fills a wide gap in the research literature and offers important terminology. It is the first to define the attributes of symbiotic care.
An integrated approach for building sustainable Islamic social finance ecosystems
Authors: Tahiri Jouti Ahmed
Published: August 2019

Purpose

Bringing more impact seems to be a real issue for social initiatives and organizations requiring the adoption of new approaches. The paper aims to define an integrated approach for building, maintaining and upgrading Islamic social finance and sustainable ecosystems.

Design/methodology/approach

The paper presents a conceptual framework based on case studies and literature review describing the methodology and the necessary steps to build sustainable ecosystems.

Findings

The paper shows the impact of building social finance ecosystems on tackling social issues. It emphasizes the idea that solving social issues is everybody’s business – from governments to businesses – and that those initiatives require sufficient Sharīʿah-compliant funding to achieve sustainability goals.

Research limitations/implications

The paper does not focus on the Islamic world experiences in building ecosystems serving social causes.

Practical implications

The paper gives an overview on how collaboration between the different social oriented organisations can enhance the social impact of the different initiatives. The aim is to ensure adequate financing to all the ecosystem components during the whole lifecycle.

Social implications

The suggested approach of building sustainable ecosystems can serve as a way to assess the existing social initiatives and practices to find relevant combinations targeting more impact.

Originality/value

In the social sphere, the idea of building ecosystems has been explored in different ways but never in a way that gathers all the components including finance providers, coordinators and the different types of initiatives. The paper adapts the ecosystem concept to the Islamic finance specificities.
Life calculation of angular contact ball bearings for industrial robot RV reducer
Authors: Deng Fukang , Li Kangchun , Hu Xiongfeng , Jiang Haifu , Huang Fuchuan
Published: August 2019

Purpose

The purpose of this paper is to analyze the force and basic rating life of angular contact ball bearings of RV reducer under the actual operating condition.

Design/methodology/approach

Force analysis of angular contact ball bearing under the actual operating condition, calculate the axial, radial load and internal load distribution, calculate the basic rating life of angular contact ball bearing under variable load conditions.

Findings

The external load has a great influence on the radial load of angular contact ball bearing, further affecting the basic rating life of angular contact ball bearing, which is a great influence on the overall life of RV reducer under the condition of high frequency and heavy load.

Originality/value

This paper provides important ideas for the design and manufacture of RV reducer in theory and experiment technology.
Linear extended state observer-based control of active lubrication for active hydrostatic journal bearing by monitoring bearing clearance
Authors: Ur Rehman Waheed , Guiyun Jiang , Yuan Xin Luo , Yongqin Wang , Iqbal Nadeem , UrRehman Shafiq , Bibi Shamsa
Published: August 2019

Purpose

This paper’s aim is modeling and simulation of an advanced controller design for a novel mechatronics system that consists of a hydrostatic journal bearing with servo control. The proposed mechatronic system has more worth in tribology applications as compared to the traditional hydrostatic bearing which has limited efficiency and poor performance because of lower stiffness and load-carrying capacity. The proposed mechatronic system takes advantage of active lubrication to improve stiffness, rotor’s stability and load-carrying capacity.

Design/methodology/approach

The current work proposes extended state observer-based controller to control the active lubrication for hydrostatic journal bearing. The advantage of using observer is to estimate unknown state variables and lumped effects because of unmodeled dynamics, model uncertainties, and unknown external disturbances. The effectiveness of the proposed mechatronic system is checked against the traditional hydrostatic bearing.

Findings

Proposed mechatronics active hydrostatic journal bearing system is checked against traditional hydrostatic journal bearing. It is found that novel active hydrostatic journal bearing with servo control has good tribology performance factors such as stiffness, less rotor vibration, no wear and friction under starting conditions and high load-carrying capacity under different conditions of spindle speed, temperature, initial oil pressure and external disturbance. The result shows that proposed mechatronics system has more worth in rotary tribology applications.

Originality/value

The current manuscript designs a novel active hydrostatic journal bearing system with servo control. The mathematical model has advantages in term of estimating unknown state variables and lumped effects because of unmodeled dynamics, model uncertainties and unknown external disturbances. The result shows improvement in dynamic characteristics of a hydrostatic journal bearing under different dynamic conditions.
Numerical investigation of tubular structures generated by cutting method and pattern scale factor (PSF) method
Authors: Ren Xin , Liu Fang Cheng , Zhang Xiang Yu , Xie Yi Min
Published: August 2019

Purpose

This paper aims to study the tensile performance, deformation characteristics, auxeticity and stability of different auxetic tubular structures generated by cutting method and pattern scale factor (PSF) method using validated finite element analysis.

Design/methodology/approach

Two types of auxetic tubular structures were designed by a coordinate transformation method and the PSF adjustment method, respectively. ABAQUS/explicit solver was used for the large deformation analysis and the displacement of key nodes was extracted to calculate Poisson’s ratio value and evaluate the deformation of tubular structures.

Findings

The random cut method was not suitable for designing auxetic tubular structures. Vertical and horizontal cut approach was suitable, but the change of the tubular diameter was lower than the tubular structures generated by the PSF adjustment method.

Research limitations/implications

Simple ways to generate auxetic tubular structure, which can be made into intelligent and foldable equipment, such as annuloplasty rings, angioplasty stents and oesophageal stents. By combined with shape memory polymer, various smart tubular materials and structures with various functions can be designed, especially in medical scaffold and other medical equipment fields.

Originality/value

The auxetic characteristic of tubular structure designed by using random cut method has been investigated for the first time. The outcome of this study would be very useful design tubular structures with better mechanical properties.
Modeling for prediction of surface roughness in milling medium density fiberboard with a parallel robot
Authors: Ayyildiz Mustafa
Published: August 2019

Purpose

This paper aims to discuss the utilization of artificial neural networks (ANNs) and multiple regression method for estimating surface roughness in milling medium density fiberboard (MDF) material with a parallel robot.

Design/methodology/approach

In ANN modeling, performance parameters such as root mean square error, mean error percentage, mean square error and correlation coefficients (R2) for the experimental data were determined based on conjugate gradient back propagation, Levenberg–Marquardt (LM), resilient back propagation, scaled conjugate gradient and quasi-Newton back propagation feed forward back propagation training algorithm with logistic transfer function.

Findings

In the ANN architecture established for the surface roughness (Ra), three neurons [cutting speed (V), feed rate (f) and depth of cut (a)] were contained in the input layer, five neurons were included in its hidden layer and one neuron was contained in the output layer (3-5-1).Trials showed that LM learning algorithm was the best learning algorithm for the surface roughness. The ANN model obtained with the LM learning algorithm yielded estimation training valuesR2(97.5 per cent) and testing valuesR2(99 per cent). TheR2for multiple regressions was obtained as 96.1 per cent.

Originality/value

The result of the surface roughness estimation model showed that the equation obtained from the multiple regressions with quadratic model had an acceptable estimation capacity. The ANN model showed a more dependable estimation when compared with the multiple regression models. Hereby, these models can be used to effectively control the milling process to reach a satisfactory surface quality.
A new measurement for yaw estimation of land vehicles using MARG sensors
Authors: Shi Gang , Li Xisheng , Wang Zhe , Liu Yanxia
Published: August 2019

Purpose

The magnetometer measurement update plays a key role in correcting yaw estimation in fusion algorithms, and hence, the yaw estimation is vulnerable to magnetic disturbances. The purpose of this study is to improve the ability of the fusion algorithm to deal with magnetic disturbances.

Design/methodology/approach

In this paper, an adaptive measurement equation based on vehicle status is derived, which can constrain the yaw estimation from drifting when vehicle is running straight. Using this new measurement, a Kalman filter-based fusion algorithm is constructed, and its performance is evaluated experimentally.

Findings

The experiments results demonstrate that the new measurement update works as an effective supplement to the magnetometer measurement update in the present of magnetic disturbances, and the proposed fusion algorithm has better yaw estimation accuracy than the conventional algorithm.

Originality/value

The paper proposes a new adaptive measurement equation for yaw estimation based on vehicle status. And, using this measurement, the fusion algorithm can not only reduce the weight of disturbed sensor measurement but also utilize the character of vehicle running to deal with magnetic disturbances. This strategy can also be used in other orientation estimation fields.
Virtual sensor for real-time estimation of the vehicle sideslip angle
Authors: Singh Kanwar Bharat
Published: August 2019

Purpose

The vehicle sideslip angle is an important state of vehicle lateral dynamics and its knowledge is crucial for the successful implementation of advanced driver-assistance systems. Measuring the vehicle sideslip angle on a production vehicle is challenging because of the exorbitant price of a physical sensor. This paper aims to present a novel framework for virtually sensing/estimating the vehicle sideslip angle. The desired level of accuracy for the estimator is to be within +/− 0.2 degree of the actual sideslip angle of the vehicle. This will make the precision of the proposed estimator at par with expensive commercially available sensors used for physically measuring the vehicle sideslip angle.

Design/methodology/approach

The proposed estimator uses an adaptive tire model in conjunction with a model-based observer. The performance of the estimator is evaluated through experimental tests on a rear-wheel drive vehicle.

Findings

Detailed experimental results show that the developed system can reliably estimate the vehicle sideslip angle during both steady state and transient maneuvers, within the desired accuracy levels.

Originality/value

This paper presents a novel framework for vehicle sideslip angle estimation. The presented framework combines an adaptive tire model, an unscented Kalman filter-based axle force observer and data from tire mounted sensors. Tire model adaptation is achieved by making extensions to the magic formula, by accounting for variations in the tire inflation pressure, load, tread-depth and temperature. Predictions with the adapted tire model were validated by running experiments on the Flat-Trac® machine. The benefits of using an adaptive tire model for sideslip angle estimation are demonstrated through experimental tests. The performance of the observer is satisfactory, in both transient and steady state maneuvers. Future work will focus on measuring tire slip angle and road friction information using tire mounted sensors and using that information to further enhance the robustness of the vehicle sideslip angle observer.
Caspase‐1 inflammasome activity in patients with Staphylococcus aureus bacteremia
Authors: Rasmussen Gunlög , Idosa Berhane Asfaw , Bäckman Anders , Monecke Stefan , Strålin Kristoffer , Särndahl Eva , Söderquist Bo
Published: August 2019

The inflammasome is a multiprotein complex that mediates caspase‐1 activation with subsequent maturation of the proinflammatory cytokines IL‐1β and IL‐18. The NLRP3 inflammasome is known to be activated by Staphylococcus aureus, one of the leading causes of bacteremia worldwide. Inflammasome activation and regulation in response to bacterial infection have been found to be of importance for a balanced host immune response. However, inflammasome signaling in vivo in humans initiated by S. aureus is currently sparsely studied. This study therefore aimed to investigate NLRP3 inflammasome activity in 20 patients with S. aureus bacteremia (SAB), by repeated measurement during the first week of bacteremia, compared with controls. Caspase‐1 activity was measured in monocytes and neutrophils by flow cytometry detecting FLICA (fluorescent‐labeled inhibitor of caspase‐1), while IL‐1β and IL‐18 was measured by Luminex and ELISA, respectively. As a measure of inflammasome priming, messenger RNA (mRNA) expression of NLRP3, CASP1 (procaspase‐1), and IL1B (pro‐IL‐1β) was analyzed by quantitative PCR. We found induced caspase‐1 activity in innate immune cells with subsequent release of IL‐18 in patients during the acute phase of bacteremia, indicating activation of the inflammasome. There was substantial interindividual variation in caspase‐1 activity between patients with SAB. We also found an altered inflammasome priming with low mRNA levels of NLRP3 accompanied by elevated mRNA levels of IL1B. This increased knowledge of the individual host immune response in SAB could provide support in the effort to optimize management and treatment of each individual patient.
Intentional Homicide: A Fifteen‐Year Study (2000–2014) at the Department of Forensic Medicine, University of Rome “Sapienza”
Authors: Cipolloni Luigi , Besi Livia , Baldari Benedetta , La Russa Raffaele , Frati Paola , Fineschi Vittorio
Published: August 2019

This study analyzes postmortem records from 260 homicide cases autopsied by the Department of Forensic Medicine in Rome from 2000 to 2014. The victims were mainly males (74%) and young (61% aged from 21 to 50 years). Although the victims were mostly Italians, the number of foreign victims (33%) has increased since 1990, primarily due to immigration. The offenders frequently used firearms (39%), particularly in multiple murders. An increase in blunt (20%) and sharp force (32%) weapons was also seen. The primary crime scene was residential (42%), and the head was the most frequently injured body region. Male victims occurred frequently in the context of organized crime (7.6%). In family or intimate‐sexual relationships, women were the majority of victims (8%). Forensic pathologists play an important role during investigation. They should consider all the information available to them, including autopsy information, crime scene information, and crime investigation data.
Plasma galectin‐3 levels do not differ in systemic lupus erythematosus patients
Authors: Zhao Chan‐Na , Mao Yan‐Mei , Liu Li‐Na , Wu Qian , Dan Yi‐Lin , Pan Hai‐Feng
Published: August 2019

Objective

To investigate the plasma galectin‐3 levels in systemic lupus erythematosus (SLE) patients and its relations with clinical and laboratory features.

Methods

A total of 180 subjects with 90 patients with SLE (8 male, 82 female, mean age 37.86 ± 13.98 years) and 90 healthy controls (8 male, 82 female, mean age 36.54 ± 10.89 years) were included. Plasma galectin‐3 levels were detected by enzyme‐linked immunosorbent assay (ELISA).

Results

There was no significant difference in age and gender distribution between SLE patients and healthy controls (both P > .05). Plasma galectin‐3 level was not significantly different between SLE patients and controls (P = .982) (P > .05). No significant difference was found regarding galectin‐3 levels between SLE with nephritis and those without nephritis (P > .05); no significant difference was found between less active SLE and more active SLE (P > .05). Galectin‐3 levels were inversely related to immune globulin M (r = −.303, P < .05), while no significant correlation between galectin‐3 levels and other quantitative laboratory parameters were observed (all P > .05).

Conclusions

In summary, plasma galectin‐3 level was not significantly different between SLE patients and controls (P = .982). Further studies are needed to elucidate the role of galectin‐3 in SLE.
Early birth is a key factor in educational disadvantage of twins: A data linkage study
Authors: Zeltzer Justin , Shand Antonia W. , Kelly Patrick , Hopper John L. , Scurrah Katrina J. , Nassar Natasha
Published: August 2019

Aim

To assess educational outcomes of twins and quantify the degree this is mediated by gestational age and other perinatal factors.

Methods

We conducted a population‐based record‐linkage cohort study of all live births ≥24 weeks gestation in New South Wales, Australia with a corresponding standardised school test result for grade 3 in 2008‐2014. The primary outcome was whether a child met the National Minimum Standard (NMS) cut‐off in literacy and numeracy domains. Robust multivariable Poisson models were used to obtain adjusted relative risks (aRRs), and mediation analysis conducted to assess contributing factors on the causal pathway.

Results

Of 351 791 liveborn infants, 10 365 (2.9%) were twins. After adjusting for maternal covariates and compared with singletons, twins had an increased risk of not meeting the NMS for all five literacy and numeracy domains (aRR 1.27‐1.45, P < .001). Gestational age alone mediated up to 73% of aRRs and small for gestational age further attenuated these effects with only minimal risk remaining after adjusting for all mediators (aRR 0.94‐1.07).

Conclusion

Almost all of the educational disadvantage experienced by twins, compared with singletons, is attributable to the risk associated with shorter gestational age, and partly by poor foetal growth. These findings support efforts to prolong gestation of twin pregnancies.
Desired vancomycin trough concentration to achieve an AUC0‐24/MIC ≥400 in Chinese children with complicated infectious diseases
Authors: Zhang Tao , Cheng Hua , Pan Zhenyu , Mi Jie , Dong Yuzhu , Zhang Ying , Sun Dan , Du Qian , Cheng Xiaoliang , Dong Yalin
Published: August 2019

A vancomycin steady‐state trough concentration (Cmin) of 15‐20 mg/L is recommended for achieving a ratio of the 24‐hour area under the curve to the minimum inhibitory concentration (AUC0‐24/MIC) of ≥400 in adults. Since few paediatric data are available, our objectives were to (a) measure the pharmacokinetic indices of vancomycin and (b) determine the correlation between Cmin and AUC0‐24/MIC in paediatric patients. Population‐based pharmacokinetic modelling was performed for paediatric patients to estimate the individual parameters. The relationship between Cmin and the calculated AUC0‐24/MIC was explored using linear regression and a probabilistic framework. A sensitivity analysis was also conducted using Monte Carlo simulations. Body‐weight significantly influenced the pharmacokinetics of vancomycin. Based on real data and simulations, Cmin ranges of 5.0‐5.9 and 9.0‐12.9 mg/L were associated with AUC0‐24/MIC ≥400 for MIC values of ≤0.5 and ≤1 mg/L, respectively. Vancomycin regimens of 10 and 15 mg/kg every 6 hours achieved a Cmin of 5.0‐5.9 mg/L and AUC0‐24/MIC ≥400 in >90% of the children when MIC was ≤0.5 mg/L. At a MIC of ≤1 mg/L, vancomycin at 15 mg/kg every 6 hours achieved Cmin of 9.0‐12.9 mg/L and AUC0‐24/MIC ≥400 in 2.0‐ and 1.6‐fold as many children compared to a dose of 10 mg/kg every 6 hours, respectively. Vancomycin Cmin values of 5.0‐12.9 mg/L were strongly predictive of achieving AUC0‐24/MIC ≥400, and rational dosing regimens of 10‐15 mg/kg q6h were required in paediatric patients, depending on the pathogen.
The prostacyclin analogue treprostinil in the treatment of pulmonary arterial hypertension
Authors: Lindegaard Pedersen Mia , Krüger Marcus , Grimm Daniela , Infanger Manfred , Wehland Markus
Published: August 2019

Pulmonary arterial hypertension (PAH) is a rare but life‐threatening disease that progresses rapidly and is currently without a cure. Pharmacological treatments aim to slow down disease progression and to reduce symptoms by targeting the prostacyclin, the endothelin or the nitric oxide pathway. Drugs targeting the prostacyclin pathway have been shown to be favourable for PAH patients by causing vasodilatative, anti‐proliferative as well as anti‐inflammatory effects, but tend to be underused, partially due to adverse effects and difficulties associated with their intravenous administration. Treprostinil, a stable prostacyclin analogue, was FDA‐approved in 2002 to improve exercise capacity in PAH patients and is available in intravenous, subcutaneous, inhaled and oral form. The four different possible ways of administration, a long half‐life and its stability at room temperature give treprostinil an advantage over epoprostenol, iloprost and selexipag, the three other FDA‐approved drugs targeting the prostacyclin pathway. In clinical trials, treprostinil improved exercise capacity, quality of life (QOL), functional class and clinical status. While the different forms of treprostinil lead to specific complications, its general adverse effects are dizziness, nausea, pain in the jaw and extremities, diarrhoea, flushing and headache. This MiniReview will assess the benefits and drawbacks of treprostinil in the treatment of PAH by examining its specific mechanism of action and pharmacological properties, such as pharmacokinetics, pharmacodynamics, adverse effects and interactions. In addition, we will analyse and discuss results from different clinical trials, comparing treprostinil's four different forms to each other as well as to other drugs targeting the prostacyclin pathway.
Biological characterization of new inhibitors of microsomal PGE synthase‐1 in preclinical models of inflammation and vascular tone
Authors: Larsson Karin , Steinmetz Julia , Bergqvist Filip , Arefin Samsul , Spahiu Linda , Wannberg Johan , Pawelzik Sven‐Christian , Morgenstern Ralf , Stenberg Patric , Kublickiene Karolina , Korotkova Marina , Jakobsson Per‐Johan
Published: August 2019

Background and Purpose

Microsomal PGE synthase‐1 (mPGES‐1), the inducible synthase that catalyses the terminal step in PGE2 biosynthesis, is of high interest as therapeutic target to treat inflammation. Inhibition of mPGES‐1 is suggested to be safer than traditional NSAIDs, and recent data demonstrate anti‐constrictive effects on vascular tone, indicating new therapeutic opportunities. However, there is a lack of potent mPGES‐1 inhibitors lacking interspecies differences for conducting in vivo studies in relevant preclinical disease models.

Experimental Approach

Potency was determined based on the reduction of PGE2 formation in recombinant enzyme assays, cellular assay, human whole blood assay, and air pouch mouse model. Anti‐inflammatory properties were assessed by acute paw swelling in a paw oedema rat model. Effect on vascular tone was determined with human ex vivo wire myography.

Key Results

We report five new mPGES‐1 inhibitors (named 934, 117, 118, 322, and 323) that selectively inhibit recombinant human and rat mPGES‐1 with IC50 values of 10–29 and 67–250 nM respectively. The compounds inhibited PGE2 production in a cellular assay (IC50 values 0.15–0.82 μM) and in a human whole blood assay (IC50 values 3.3–8.7 μM). Moreover, the compounds blocked PGE2 formation in an air pouch mouse model and reduced acute paw swelling in a paw oedema rat model. Human ex vivo wire myography analysis showed reduced adrenergic vasoconstriction after incubation with the compounds.

Conclusion and Implications

These mPGES‐1 inhibitors can be used as refined tools in further investigations of the role of mPGES‐1 in inflammation and microvascular disease.
Reevaluation of genetic variants previously associated with arrhythmogenic right ventricular cardiomyopathy integrating population‐based cohorts and proteomics data
Authors: Ye Johan Z. , Delmar Mario , Lundby Alicia , Olesen Morten S.
Published: August 2019

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is one of the most common causes of sudden cardiac death in young people. Patients diagnosed with ARVC may experience increased likelihood of development of anxiety and depression, emphasizing the need for accurate diagnosis. To assist future genetic diagnosis and avoidance of misdiagnosis, we evaluated the reported monogenic disease‐causing variants in ARVD/C Genetic Variants Database, Human Gene Mutation Database, and ClinVar. Within the aforementioned databases, 630 monogenic disease‐causing variants from 18 genes were identified. In the genome Aggregation Database, 226 of these were identified; 68 of which were found at greater than expected prevalence. Furthermore, 37/226 genetic variants were identified amongst the 409 000 UK biobank participants, 23 were not associated with ARVC. Among the 14 remaining variants, 13 were previously found with greater than expected prevalence for a monogenic variant. Nevertheless, they were associated with serious cardiac phenotypes, suggesting that these 13 variants may be disease‐modifiers of ARVC, rather than monogenic disease‐causing. In summary, more than 10% of variants previously reported to cause ARVC were found unlikely to be associated with highly penetrant monogenic forms of ARVC. Notably, all variants in OBSCN and MYBPC3 were found, making these unlikely to be monogenic causes of ARVC.