bluuebunny/crossref_metadata_2025 huggingface dataset:
Spawning season movements of transported landlocked Atlantic salmon in a newly restored river habitat
Authors: Hatanpää Aurora , Huuskonen Hannu , Janhunen Matti , Kortet Raine , Piironen Jorma
Published: October 2020

Certain spawning areas of the critically endangered Lake Saimaa landlocked Atlantic salmon (Salmo salar m. sebago) have been recently restored by excavator- and helicopter-scattered gravel, but the success of applied methodologies has remained open. Here, we monitored the spawning-related movements and redds occurrence of transported semi-wild and hatchery-reared salmon in the restored River Ala-Koitajoki, eastern Finland, using radiotelemetry and snorkeling. Nearly all fish accepted the newly restored spawning habitats in the river that maintains a low flow rate (only 4 m3·s−1). The movements of females released up to 2 weeks before spawning time were restricted mainly to the closest rapids from the release site, and most of the movements were directed downstream. Semi-wild and hatchery background fish exhibited similar mobility, which was more variable among males. A majority of redds were found in restored areas, and both helicopter- and excavator-scattered gravels were accepted as spawning substrates. Our results indicate that natural reproduction of the studied landlocked salmon population can be successfully returned to its original spawning river by restoration of habitats and transfer of spawners.
HL-LHC and ILC sensitivities in the hunt for heavy Higgs bosons
Authors: Bahl Henning , Bechtle Philip , Heinemeyer Sven , Liebler Stefan , Stefaniak Tim , Weiglein Georg
Published: October 2020

The prediction of additional Higgs bosons is one of the key features of physics beyond the Standard Model (SM) that gives rise to an extended Higgs sector. We assess the sensitivity of the Large Hadron Collider (LHC) in the high luminosity (HL) run alone and in combination with a possible future International Linear Collider (ILC) to probe heavy neutral Higgs bosons. We employ the Minimal Supersymmetric Standard Model (MSSM) as a framework and assume the light$$\mathcal {CP}$$CP-even MSSM Higgs boson to be the Higgs boson observed at$$125\,\mathrm{GeV}$$125GeV. We discuss the constraints on the MSSM parameter space arising from the precision measurements of the rates of the detected signal at$$125\,\mathrm{GeV}$$125GeVand from direct searches for new heavy Higgs bosons in the$$\tau ^+\tau ^-$$τ+τ-,$$b\bar{b}$$bb¯and di-Higgs (hh) final states. A new benchmark scenario for heavy Higgs searches in the$$b\bar{b}$$bb¯channel is proposed in this context. For the future Higgs rate measurements at the HL-LHC and ILC two different scenarios are investigated, namely the case where the future rate measurements agree with the SM prediction and the case where the rates agree with the predictions of possible realizations of the MSSM Higgs sector in nature.
Highly accurate technique for studying some chaotic models described by ABC-fractional differential equations of variable-order
Authors: Khader M. M. , Al-Dayel Ibrahim
Published: October 2020

The propose of this paper is to introduce and investigate a highly accurate technique for solving the fractional Logistic and Ricatti differential equations of variable-order. We consider these models with the most common nonsingular Atangana–Baleanu–Caputo (ABC) fractional derivative which depends on the Mittag–Leffler kernel. The proposed numerical technique is based upon the fundamental theorem of the fractional calculus as well as the Lagrange polynomial interpolation. We satisfy the efficiency and the accuracy of the given procedure; and study the effect of the variation of the fractional-order [Formula: see text] on the behavior of the solutions due to the presence of ABC-operator by evaluating the solution with different values of [Formula: see text]. The results show that the given procedure is an easy and efficient tool to investigate the solution for such models. We compare the numerical solutions with the exact solution, thereby showing excellent agreement which we have found by applying the ABC-derivatives. We observe the chaotic solutions with some fractional-variable-order functions.
An unpublished theorem of Solovay on OD partitions of reals into two non-OD parts, revisited
Authors: Enayat Ali , Kanovei Vladimir
Published: October 2020

A definable pair of disjoint non-OD sets of reals (hence, indiscernible sets) exists in the Sacks and 𝔼0-large generic extensions of the constructible universe L. More specifically, if [Formula: see text] is either Sacks generic or 𝔼0-large generic real over L, then it is true in L[a] that there is a lightface [Formula: see text] equivalence relation [Formula: see text] on the [Formula: see text] set [Formula: see text] with exactly two equivalence classes, and both those classes are non-OD sets.
A Method to Estimate Dynamic Buckling Response of an Unstiffened Plate Elastically Restrained Along All Edges Under In-Plane Impact
Authors: Yang Bin , Fu Kunkun , Li Yan
Published: October 2020

Unstiffened plates in structures are usually welded or fastened to supporting members, providing rotational restraint stiffness to the plate. Previous studies have shown that neglect of rotational restraint stiffness at the edges of a plate in a structure can introduce deviations in the analysis of dynamic elastic buckling. In this study, the in-plane impact-induced dynamic elastic buckling responses of isotropic imperfect unstiffened plates with four elastically restrained edges are analytically investigated, based on the large-deflection theory of thin plate. The evolution of the peak deflection predicted by the proposed analytical method is found to be consistent with the responses available from the literature. Then the method is further used to estimate the deformation map of an unstiffened plate with four elastically restrained edges, and the effects of rotational restraint stiffness, initial geometric imperfection and shock duration on the dynamic buckling response of the plate are examined. The results show that the critical dynamic buckling load and the maximum deflection response of the plates are significantly influenced by the rotational restraint stiffness as well as the first-order initial geometric imperfection, and thus cannot be neglected in the analysis of dynamic buckling.
Structural Behaviors of Integrally-Jointed Plywood Columns with Knot Defects
Authors: Xin Zhuoyang , Gattas Joseph
Published: October 2020

Modern factory automation is enabling the economic production of timber building components with sophisticated integral mechanical joints. This paper investigates the governing compressive failure mechanisms of full-length integrally-jointed plywood box columns, and in particular seeks to understand the interaction between localized material knot defects, integral box joint capacity, and column strength. A new critical failure mechanism is identified based on experimental observations and numerical analysis of sections with varying sizes of knot defect, with column capacity governed by defect-induced transverse loading of integral box joints. Column capacity was shown to improve with localized joint strengthening in knot-defective regions, or with a defect-adaptive fabrication procedure that avoids identified defects during component plate machining. The new failure mechanism was also combined with prior understanding of plate buckling and pop-off failure mechanisms to propose an overall failure process for integrally-jointed plywood columns. Results from this paper can also inform development of other types of integrally-jointed thin-walled structures.
A Novel Method to Identify Golgi Protein Types Based on Hybrid Feature and SVM Algorithm
Authors: Ma Liang , Jiang Hailin , Yang Wanli , Zhu Quanjie
Published: October 2020

Accurate identification of Golgi protein types can provide useful clues to reveal the correlation between GA dysfunction and disease pathology and improve the ability to develop more effective treatments for the diseases. This paper introduces an effective and robust method to classify Golgi protein type with traditional machine learning algorithms. In which various features such as n-GDip, DCCA, psePSSM were used as training features and SVM with linear kernel was employed as a classifier. To solve the imbalance problem of the benchmark datasets, the oversampling technique SMOTE was adopted. To deal with the huge amount of features, the PCA algorithm and Fisher feature selection method were adopted to reduce feature dimensions and remove redundant features. The experimental results show that the proposed method had a further improvement compared with other traditional machine learning methods in 10-fold cross-validation, Jackknife cross-validation and independent testing, which means a further step for the clinical application of computational methods to predict the Golgi protein types.
Hybrid Finite Element Analysis of Heat Conduction in Orthotropic Media with Variable Thermal Conductivities
Authors: Qiu Wenkai , Wang Keyong , Li Peichao
Published: October 2020

A hybrid finite element method is proposed for the heat conduction analysis with variable thermal conductivities. A linear combination of fundamental solutions is employed to approximate the intra-element temperature field while standard one-dimensional shape functions are utilized to independently define the frame temperature field along the element boundary. The influence of variable thermal conductivities embeds in the intra-element temperature field via the fundamental solution. A hybrid variational functional, which involves integrals along the element boundary only, is developed to link the two assumed fields to produce the thermal stiffness equation. The advantage of the proposed method lies that the changes in the thermal conductivity are captured inside the element domain. Numerical examples demonstrate the accuracy and efficiency of the proposed method and also the insensitivity to mesh distortion.
Modeling of Damage Evolution in a Patient-Specific Stenosed Artery upon Stent Deployment
Authors: Rouhani Fatemeh , Fereidoonnezhad Behrooz , Zakerzadeh Mohammad Reza , Baghani Mostafa
Published: October 2020

Computational models provide a powerful tool for pre-clinical assessment of medical devices and early evaluation of potential risks to the patient in terms of plaque fragmentation and in-stent restenosis (ISR). Using a suitable constitutive model for arterial tissue is key for the development of a reliable computational model. Although some inelastic phenomena such as stress softening and permanent deformation likely occur due to the supra-physiological loading of arterial tissue during the stenting procedure, hyperelastic constitutive models have been employed in most of the previously developed computational models. This study presents a finite element model for stent deployment into a patient-specific stenosed artery while inelastic arterial behaviors due to supra-physiological loading of the tissue have been considered. Specifically, the maximum stress in the plaque and the arterial layers which is the main cause of plaque fracture during stent deployment and the surgically-induced injury (damage) in the arterial wall, as the main cause of ISR, are presented. The results are compared with the commonly-used hyperelastic behavior for arterial layers. Furthermore, the effects of arterial material parameter variation, analogues to different patients, are investigated. A higher amount of damage is predicted for the artery which shows a higher stress in a specific strain.
Additive Manufacturing Enabled Supply Chain in Combating COVID-19
Authors: Arora Ranjan , Arora Pawan K , Kumar Harish , Pant Meena
Published: October 2020

Additive manufacturing (AM) is a method in which three-dimensional structures are successively laid down to create a solid object. The inherent advantages of AM technology are successfully drafted and exploited by the different organization across the globe. During the time of pandemic i.e. COVID-19, 3D printing has come to rescue and has been used for manufacturing critical medical supplies. 3D printing has been used in manufacturing some of the critical items like ventilators valves, face shields, swabs, oxygen valves, hand sanitizer holders, 3-DP lung models, etc. The main reason for its success has been the ability of 3D printing to print locally by using digital designs and thus reducing the number of supply chain actors. Also, the ability of 3D printing to manufacture/print complex geometrical designs locally is the main reason for its successful adoption during COVID-19. In this paper, we have discussed how AM has come to the forefront in fighting this pandemic. Various AM techniques have played a critical role in bridging the supply chain gap in the medical industry and locally printing critical devices. There were certain apprehensions before the pandemic along with slow adoption but this pandemic has also increased the adoption of AM due to its ability to overcome the demand created by COVID-19.
Dr Dorothy Helen Rayner FGS (1912–2003): vertebrate palaeontologist and academic
Authors: Boylan Patrick J.
Published: October 2020

Dorothy Rayner was one of the first women to be appointed to a tenured academic post in any English university geology department, joining the Geology Department of the University of Leeds in 1939 and serving for 38 years to her retirement in 1977. She had two very important early influences in her life. The first was her family, with its tradition through several generations of doctors, scientists, engineers, mathematicians, radical politics and social activism. The other was her earlier education, particularly her 7 years at the very influential Bedales School, the first of what were to become known in the twentieth century as ‘progressive’ schools. After gaining a First at Girton College in the Cambridge Natural Sciences Tripos, she undertook ground-breaking research on the taxonomy and neural systems of Jurassic fishes, for which she was awarded a Cambridge PhD in 1938, soon after which she was appointed Assistant Lecturer in Geology at Leeds. In addition to an always very heavy teaching load, she continued with a broad range of research, including further work on fossil vertebrates, and the stratigraphy of first the north of England and then the whole of the British Isles. She was also an outstanding Editor, and then President, of the Yorkshire Geological Society.
Multiple Elimination of Base Classifiers in Ensemble Learning Using Accuracy and Diversity Comparisons
Authors: Jan Zohaib Md. , Verma Brijesh
Published: October 2020

When generating ensemble classifiers, selecting the best set of classifiers from the base classifier pool is considered a combinatorial problem and an efficient classifier selection methodology must be utilized. Different researchers have used different strategies such as evolutionary algorithms, genetic algorithms, rule-based algorithms, simulated annealing, and so forth to select the best set of classifiers that can maximize overall ensemble classifier accuracy. In this article, we present a novel classifier selection approach to generate an ensemble classifier. The proposed approach selects classifiers in multiple rounds of elimination. In each round, a classifier is given a chance to be selected to become a part of the ensemble, if it can contribute to the overall ensemble accuracy or diversity; otherwise, it is put back into the pool. Each classifier is given multiple opportunities to participate in rounds of selection and they are discarded only if they have no remaining chances. The process is repeated until no classifier in the pool has any chance left to participate in the round of selection. To test the efficacy of the proposed approach, 13 benchmark datasets from the UCI repository are used and results are compared with single classifier models and existing state-of-the-art ensemble classifier approaches. Statistical significance testing is conducted to further validate the results, and an analysis is provided.
Exploring mechanistic links between extracellular branched-chain amino acids and muscle insulin resistance: an in vitro approach
Authors: Crossland Hannah , Smith Kenneth , Idris Iskandar , Phillips Bethan E. , Atherton Philip J. , Wilkinson Daniel J.
Published: October 2020

Branched-chain amino acids (BCAAs) are essential for critical metabolic processes; however, recent studies have associated elevated plasma BCAA levels with increased risk of insulin resistance. Using skeletal muscle cells, we aimed to determine whether continued exposure of high extracellular BCAA would result in impaired insulin signaling and whether the compound sodium phenylbutyrate (PB), which induces BCAA metabolism, would lower extracellular BCAA, thereby alleviating their potentially inhibitory effects on insulin-mediated signaling. Prolonged exposure of elevated BCAA to cells resulted in impaired insulin receptor substrate 1/AKT signaling and insulin-stimulated glycogen synthesis. PB significantly reduced media BCAA and branched-chain keto acid concentrations and increased phosphorylation of AKT [+2.0 ± 0.1-fold; P < 0.001 versus without (−)PB] and AS160 (+3.2 ± 0.2-fold; P < 0.001 versus −PB); however, insulin-stimulated glycogen synthesis was further reduced upon PB treatment. Continued exposure of high BCAA resulted in impaired intracellular insulin signaling and glycogen synthesis, and while forcing BCAA catabolism using PB resulted in increases in proteins important for regulating glucose uptake, PB did not prevent the impairments in glycogen synthesis with BCAA exposure.
Role and mechanisms of exosomal miRNAs in IBD pathophysiology
Authors: Wani Sameena , Man Law Ivy Ka , Pothoulakis Charalabos
Published: October 2020

Exosomes represent secretory membranous vesicles used for the information exchange between cells and organ-to-organ communication. Exosome crosstalk mechanisms are involved in the regulation of several inflammatory bowel disease (IBD)-associated pathophysiological intestinal processes such as barrier function, immune responses, and intestinal flora. Functional biomolecules, mainly noncoding RNAs (ncRNAs), are believed to be transmitted between the mammalian cells via exosomes that likely play important roles in cell-to-cell communication, both locally and systemically. MicroRNAs (miRNAs) encapsulated in exosomes have generated substantial interest because of their critical roles in multiple pathophysiological processes. In addition, exosomal miRNAs are implicated in the gut health. MiRNAs are selectively and actively loaded into the exosomes and then transferred to the target recipient cell where they manipulate cell function through posttranscriptional silencing of target genes. Intriguingly, miRNA profile of exosomes differs from their cellular counterparts suggesting an active sorting and packaging mechanism of exosomal miRNAs. Even more exciting is the involvement of posttranscriptional modifications in the specific loading of miRNAs into exosomes, but the underlying mechanisms of how these modifications direct ncRNA sorting have not been established. This review gives a brief overview of the status of exosomes and exosomal miRNAs in IBD and also discusses potential mechanisms of exosomal miRNA sorting and delivering.
Compartment-specific transcriptomics of ozone-exposed murine lungs reveals sex- and cell type-associated perturbations relevant to mucoinflammatory lung diseases
Authors: Choudhary Ishita , Vo Thao , Paudel Kshitiz , Patial Sonika , Saini Yogesh
Published: October 2020

Ozone is known to cause lung injury, and resident cells of the respiratory tract (i.e., epithelial cells and macrophages) respond to inhaled ozone in a variety of ways that affect their survival, morphology, and functioning. However, a complete understanding of the sex-associated and the cell type-specific gene expression changes in response to ozone exposure is still limited. Through transcriptome profiling, we aimed to analyze gene expression alterations and associated enrichment of biological pathways in three distinct cell type-enriched compartments of ozone-exposed murine lungs. We subchronically exposed adult male and female mice to 0.8 ppm ozone or filtered air. RNA-Seq was performed on airway epithelium-enriched airways, parenchyma, and purified airspace macrophages. Differential gene expression and biological pathway analyses were performed and supported by cellular and immunohistochemical analyses. While a majority of differentially expressed genes (DEGs) in ozone-exposed versus air-exposed groups were common between both sexes, sex-specific DEGs were also identified in all of the three tissue compartments. As compared with ozone-exposed males, ozone-exposed females had significant alterations in gene expression in three compartments. Pathways relevant to cell division and DNA repair were enriched in the ozone-exposed airways, indicating ozone-induced airway injury and repair, which was further supported by immunohistochemical analyses. In addition to cell division and DNA repair pathways, inflammatory pathways were also enriched within the parenchyma, supporting contribution by both epithelial and immune cells. Further, immune response and cytokine-cytokine receptor interactions were enriched in macrophages, indicating ozone-induced macrophage activation. Finally, our analyses also revealed the overall upregulation of mucoinflammation- and mucous cell metaplasia-associated pathways following ozone exposure.
Expectant Management of Monochorionic-Triamniotic Triplets Complicated by Selective In Utero Growth Restriction: Report of 2 Cases
Authors: Carmant Laurence , Wavrant Sandrine , Codsi Elisabeth
Published: October 2020

The optimal management of monochorionic-triamniotic (MCTA) triplet pregnancies is not clearly established, and there is no literature to guide management of MCTA complicated with selective intrauterine growth restriction (sIUGR). This gap in knowledge and the concern for higher risk of severe complications have led some medical societies to recommend selective termination of nontrichorionic triplet pregnancies. We sought to report the favourable outcomes of two MCTA complicated by sIUGR expectantly managed at Sainte-Justine Hospital, Montreal, Canada. The first case is of a 42-year-old woman with spontaneous MCTA triplets diagnosed at 18 weeks with type II sIUGR who opted for expectant management. The second patient was a 22-year-old woman with a spontaneous MCTA triplet pregnancy diagnosed at 18 weeks with type III sIUGR. Our experience shows that close serial ultrasounds could potentially allow physicians to foresee fetal deterioration. In our opinion, expectant management should be considered as a management option for MCTA complicated by sIUGR.
Prevalence of Spina Bifida among Newborns in Africa: A Systematic Review and Meta-Analysis
Authors: Oumer Mohammed , Taye Molla , Aragie Hailu , Tazebew Ashenafi
Published: October 2020

Spina bifida is an abnormal closure of the neural tube during the fourth week of development. It is the major cause of fetal loss and considerable disabilities in newborns. The aim of this review is to determine the pooled prevalence of spina bifida among newborns in Africa. PubMed/Medline, Google Scholar, Science Direct, Joanna Briggs Institute (JBI) Library, Cochrane Library, Web of Science, African Journals Online, and Embase databases were systematically searched. Cochran Q test and I2 test statistics were applied to assess heterogeneity across studies. A random-effect model was applied to calculate the pooled prevalence of spina bifida. Forest plot and Galbraith’s plot were used to visualize heterogeneity. Subgroup, sensitivity, meta-regression, and meta-cumulative analyses were performed. All essential data were extracted using a standardized data extraction format, and the JBI quality appraisal checklist was used to assess the quality of studies. Egger’s test and Begg’s test were used in order to detect the publication bias. In the present systematic review and meta-analysis, 6,587,298 births in twenty-seven studies were included. The pooled birth prevalence of spina bifida in Africa was 0.13% with a range between 0.12% and 0.14%. In Africa, the highest burden of spina bifida was detected in Algeria (0.43%), Ethiopia (0.32%), Tanzania (0.26%), Cameron (0.12%), Egypt (0.10%), and South Africa (0.10%). The lowest burden of spina bifida was detected in Libya (0.006%) and Tunisia (0.009%). The high birth prevalence of spina bifida was detected in Africa. There was a significant variation in the prevalence of spina bifida among study countries in Africa. The authors recommend that special awareness creation with the help of health education intervention should be provided for mothers to focus on prevention in order to reduce the burden of spina bifida.
Modelling and Simulating the Novel Coronavirus with Implications of Asymptomatic Carriers
Authors: Benrhmach Ghassane , Namir Khalil , Bouyaghroumni Jamal
Published: October 2020

The World Health Organization declared that the total number of confirmed cases tested positive for SARS‐CoV‐2, affecting 210 countries, exceeded 3 million on 29 April 2020, with more than 207,973 deaths. In order to end the global COVID‐19 pandemic, public authorities have put in place multiple strategies like testing, contact tracing, and social distancing. Predictive mathematical models for epidemics are fundamental to understand the development of the epidemic and to plan effective control strategies. Some hosts may carry SARS‐CoV‐2 and transmit it to others, yet display no symptoms themselves. We propose applying a model (SELIAHRD) taking in consideration the number of asymptomatic infected people. The SELIAHRD model consists of eight stages: Susceptible, Exposed, Latent, Symptomatic Infected, Asymptomatic Infected, Hospitalized, Recovered, and Dead. The asymptomatic carriers contribute to the spread of disease, but go largely undetected and can therefore undermine efforts to control transmission. The simulation of possible scenarios of the implementation of social distancing shows that if we rigorously follow the social distancing rule then the healthcare system will not be overloaded.
Multistage Estimators for the Distributed Drive Articulated Steering Vehicle
Authors: Gao Guangzong , Wang Jixin , Ma Tao , Liu Wenzhong , Lei Tianlong
Published: October 2020

The distributed drive articulated steering vehicle (DDASV) has a broad application prospect in the field of special operations. It is essential to obtain accurate vehicle states for better effect of active control. DDASV dynamic model is presented. To improve robustness, an adaptive strong tracking algorithm is applied to the singular value decomposition unscented Kalman filter (SVDUKF). Divided by yaw rate sensors and the tire models, two multistage estimators are established for DDASVs. Stable steering condition is simulated to investigate the influence on the estimated accuracy about the sensors and tire models. The velocities and tire forces are the key parameters to be estimated. The performance of each estimator regarding the practicability and accuracy is compared. The results show that all estimators are practicable. However, the accuracy of the estimated velocities based on yaw rate sensors is better and the transient tire model can improve the accuracy of estimated lateral forces more effectively for the estimator established with yaw rate sensors.
Cognitive Reserve and Executive Functions in Adults with Type 2 Diabetes
Authors: Peña-González Paola , Mondragón-Maya Alejandra , Silva-Pereyra Juan , Roa-Rojas Paloma
Published: October 2020

Background. Adults with type two diabetes mellitus (DM2) show cognitive deficits within the executive function domain. The detrimental effects of DM2 over executive function (EF) performance may be mediated by factors such as cognitive reserve (CR). CR mediates cognitive performance by delaying the appearance of clinical symptoms from subjacent brain pathology or attenuating the severity of such symptoms. Our main goal was to study the effects of CR on executive functions of adults with DM2. Methods. Data from a total of 1,034 adults were included (362 women, 672 men). Subjects were categorized into four groups: subjects with DM2 and high CR (

n
=
235

), control subjects with high CR (

n
=
265

), subjects with DM2 and low CR (

n
=
298

), and control subjects with low CR (

n
=
236

). CR was quantified through 3 proxies: education, occupational complexity, and leisure activities. Executive functions were evaluated through visual scanning, verbal fluency, and backwards counting tasks. First, a series of four one-way ANOVAs was performed where group was included as a between-subject factor and executive function as a dependent variable. Second, a hierarchical multiple regression analysis was conducted to assess the weight of each CR proxy on EF performance. Results. CR level significantly affected all executive function scores independently of the diabetes status. Hierarchical regression analyses indicated that years of education accounted for most of the variance in the model for executive function performance. In this study, we found that there is a significant effect of CR on executive function performance of DM2 subjects and education is the most important CR proxy.
An Accelerated Conjugate Gradient Algorithm for Solving Nonlinear Monotone Equations and Image Restoration Problems
Authors: Feng Haishan , Li Tingting
Published: October 2020

Combining the three-term conjugate gradient method of Yuan and Zhang and the acceleration step length of Andrei with the hyperplane projection method of Solodov and Svaiter, we propose an accelerated conjugate gradient algorithm for solving nonlinear monotone equations in this paper. The presented algorithm has the following properties: (i) All search directions generated by the algorithm satisfy the sufficient descent and trust region properties independent of the line search technique. (ii) A derivative-free search technique is proposed along the direction to obtain the step length αk. (iii) If ϕk=−αkhk−hwkTdk>0, then an acceleration scheme is used to modify the step length in a multiplicative manner and create a point. (iv) If the point satisfies the given condition, then it is the next point; otherwise, the hyperplane projection technique is used to obtain the next point. (v) The global convergence of the proposed algorithm is established under some suitable conditions. Numerical comparisons with other conjugate gradient algorithms show that the accelerated computing scheme is more competitive. In addition, the presented algorithm can also be applied to image restoration.
Development of Kaolin Clay as a Cost-Effective Technology for Defluoridation of Groundwater
Authors: Ayalew Adane Adugna
Published: October 2020

Excessive fluoride in potable groundwater is a serious health problem in rural areas of many developing countries. The presence of a small amount of fluoride in potable water is beneficial to human health, but a high amount (>1.5 mg/L) has adverse effects. The present study is aimed to prepare a new cost-effective adsorbent of kaolin clay that can be used as a valuable defluoridating agent. Characterization of the prepared adsorbent was carried out using DSC, FTIR, TGA, and XRD. Also, the surface area of the adsorbent was measured by BET analysis. The clay was activated with concentrated H2SO4, and the effects of various experimental parameters such as temperature (25, 40, 50, and 60°C), pH (2, 4, 6, and 8), particle size (<0.075, 0.075–0.15, and 0.15–0.30 mm), contact time (30, 60, 90, 120, and 150 min), and dose of the adsorbents (0.5, 1, 1.5, 2.0, and 2.5 g) were investigated using a batch adsorption method. The specific surface area of raw and activated clay was found to be 10.598 m2/g and 5.258 m2/g, respectively. The optimum fluoride removal by both adsorbents was obtained at pH 4, temperature 50°C, particle size 0.075 mm, and 60 min. In both adsorbents, the degree of fluoride removal was increased with a decrease in the particle size of the adsorbent and increased contact time and dosage of the adsorbent. In all parameters, adsorption by activated clay was better than raw kaolin clay for retaining fluoride. The obtained data were well fitted with Freundlich and Langmuir isotherm models.
Numerical Analysis of the Blast Wave Propagation due to Various Explosive Charges
Authors: Figuli Lucia , Cekerevac Damjan , Bedon Chiara , Leitner Bohuš
Published: October 2020

Blast events and scenarios, as known, represent extreme phenomena that may result in catastrophic consequences, both for humans and structures. Accordingly, for engineering applications, the reliable description of expected blast waves is a crucial step of the overall design process. Compared to ideal theoretical formulations, however, real explosive events can be strongly sensitive to a multitude of parameters and first of all to the basic features (size, type, shape, etc.) of the charge. In this regard, several advanced computer codes can be used in support of design and research developments. Besides, the input parameters and solving assumptions of refined numerical methods are often available and calibrated in the literature for specific configurations only. In this paper, with the support of the ANSYS Autodyn program, special care is dedicated to the numerical analysis of the blast wave propagation in the air due to several charges. Five different explosives are taken into account in this study, including RDX, DAP‐2, DAP‐E, Polonit‐V, and homemade ANFO. The effects of different mixtures are thus emphasized in terms of the predicted blast wave, as a function of a given control point, direction, explosive mass, and composition. As shown, relatively scattered peak pressure estimates are collected for a given explosive. Comparative results are hence proposed towards selected experimental data of the literature, as well as based on simple analytical predictions. The collected overpressure peak values are thus discussed for the selected explosive charges.
Preclinical Comparison of the Blood–brain barrier Permeability of Osimertinib with Other EGFR TKIs
Authors: Colclough Nicola , Chen Kan , Johnström Peter , Strittmatter Nicole , Yan Yumei , Wrigley Gail L. , Schou Magnus , Goodwin Richard , Varnäs Katarina , Adua Sally J. , Zhao Minghui , Nguyen Don X. , Maglennon Gareth , Barton Peter , Atkinson James , Zhang Lin , Janefeldt Annika , Wilson Joanne , Smith Aaron , Takano Akihiro , Arakawa Ryosuke , Kondrashov Mikhail , Malmquist Jonas , Revunov Evgeny , Vazquez-Romero Ana , Moein Mohammad Mahdi , Windhorst Albert D. , Karp Natasha A. , Finlay M. Raymond V. , Ward Richard A. , Yates James W.T. , Smith Paul D. , Farde Lars , Cheng Zack , Cross Darren A.E.
Published: October 2020

Purpose:

Osimertinib is a potent and selective EGFR tyrosine kinase inhibitor (EGFR-TKI) of both sensitizing and T790M resistance mutations. To treat metastatic brain disease, blood–brain barrier (BBB) permeability is considered desirable for increasing clinical efficacy.

Experimental Design:

We examined the level of brain penetration for 16 irreversible and reversible EGFR-TKIs using multiple in vitro and in vivo BBB preclinical models.

Results:

In vitro osimertinib was the weakest substrate for human BBB efflux transporters (efflux ratio 3.2). In vivo rat free brain to free plasma ratios (Kpuu) show osimertinib has the most BBB penetrance (0.21), compared with the other TKIs (Kpuu ≤ 0.12). PET imaging in Cynomolgus macaques demonstrated osimertinib was the only TKI among those tested to achieve significant brain penetrance (Cmax %ID 1.5, brain/blood Kp 2.6). Desorption electrospray ionization mass spectroscopy images of brains from mouse PC9 macrometastases models showed osimertinib readily distributes across both healthy brain and tumor tissue. Comparison of osimertinib with the poorly BBB penetrant afatinib in a mouse PC9 model of subclinical brain metastases showed only osimertinib has a significant effect on rate of brain tumor growth.

Conclusions:

These preclinical studies indicate that osimertinib can achieve significant exposure in the brain compared with the other EGFR-TKIs tested and supports the ongoing clinical evaluation of osimertinib for the treatment of EGFR-mutant brain metastasis. This work also demonstrates the link between low in vitro transporter efflux ratios and increased brain penetrance in vivo supporting the use of in vitro transporter assays as an early screen in drug discovery.
Improved Survival Associated with Local Tumor Response Following Multisite Radiotherapy and Pembrolizumab: Secondary Analysis of a Phase I Trial
Authors: Luke Jason J. , Onderdonk Benjamin E. , Bhave Sandeep R. , Karrison Theodore , Lemons Jeffrey M. , Chang Paul , Zha Yuanyuan , Carll Tim , Krausz Thomas , Huang Lei , Martinez Carlos , Janisch Linda A. , Hseu Robyn D. , Moroney John W. , Patel Jyoti D. , Khodarev Nikolai N. , Salama Joseph K. , Ott Patrick A. , Fleming Gini F. , Gajewski Thomas F. , Weichselbaum Ralph R. , Pitroda Sean P. , Chmura Steven J.
Published: October 2020

Purpose:

Multisite stereotactic body radiotherapy followed by pembrolizumab (SBRT+P) has demonstrated safety in advanced solid tumors (ASTs). However, no studies have examined the relationships between irradiated tumor response, SBRT-induced tumor gene expression, and overall survival (OS).

Patients and Methods:

Patients with AST received SBRT (30–50 Gy in 3–5 fractions) to two to four metastases followed by pembrolizumab (200 mg i.v. every 3 weeks). SBRT was prescribed to a maximum tumor volume of 65 mL. Small metastases received the complete prescribed coverage (complete-Rx), while larger metastases received partial coverage (partial-Rx). Treated metastasis control (TMC) was defined as a lack of progression for an irradiated metastasis. Landmark analysis was used to assess the relationship between TMC and OS. Thirty-five biopsies were obtained from 24 patients: 19 pre-SBRT and 16 post-SBRT (11 matched) prior to pembrolizumab and were analyzed via RNA microarray.

Results:

Sixty-eight patients (139 metastases) were enrolled with a median follow-up of 10.4 months. One-year TMC was 89.5% with no difference between complete-Rx or partial-Rx. On multivariable analysis, TMC was independently associated with a reduced risk for death (HR, 0.36; 95% confidence interval, 0.17–0.75; P = 0.006). SBRT increased expression of innate and adaptive immune genes and concomitantly decreased expression of cell cycle and DNA repair genes in the irradiated tumors. Elevated post-SBRT expression of DNASE1 correlated with increased expression of cytolytic T-cell genes and irradiated tumor response.

Conclusions:

In the context of SBRT+P, TMC independently correlates with OS. SBRT impacts intratumoral immune gene expression associated with TMC. Randomized trials are needed to validate these findings.
Spatiotemporal Heterogeneity in Multiparametric Physiologic MRI Is Associated with Patient Outcomes in IDH-Wildtype Glioblastoma
Authors: Park Ji Eun , Kim Ho Sung , Kim NakYoung , Park Seo Young , Kim Young-Hoon , Kim Jeong Hoon
Published: October 2020

Purpose:

Heterogeneity in glioblastomas is associated with poorer outcomes, and physiologic heterogeneity can be quantified with noninvasive imaging. We developed spatial habitats based on multiparametric physiologic MRI and evaluated associations between temporal changes in these habitats and progression-free survival (PFS) after concurrent chemoradiotherapy (CCRT) in patients with glioblastoma.

Experimental Design:

Ninety-seven patients with isocitrate dehydrogenase (IDH)-wildtype glioblastoma were enrolled and two serial MRI examinations after CCRT were analyzed. Cerebral blood volumes and apparent diffusion coefficients were grouped using k-means clustering into three spatial habitats. Associations between temporal changes in spatial habitats and PFS were investigated using Cox proportional hazard modeling. The performance of significant predictors for PFS and overall survival (OS) was measured using a discrete increase of habitat (habitat risk score) in a temporal validation set from a prospective registry (n = 53, ClinicalTrials.gov NCT02619890). The site of progression was matched with the spatiotemporal habitats.

Results:

Three spatial habitats of hypervascular cellular, hypovascular cellular, and nonviable tissue were identified. A short-term increase in the hypervascular cellular habitat (HR, 40.0; P = 0.001) and hypovascular cellular habitat was significantly associated with shorter PFS (HR, 3.78; P < 0.001) after CCRT. Combined with clinical predictors, the habitat risk score showed a C-index of 0.79 for PFS and 0.74 for OS and stratified patients with short, intermediate, and long PFS (P = 0.016). An increase in the hypovascular cellular habitat predicted tumor progression sites.

Conclusions:

Hypovascular cellular habitats derived from multiparametric physiologic MRIs may be useful predictors of clinical outcomes in patients with posttreatment glioblastoma.
Dual Functional States of R406W-Desmin Assembly Complexes Cause Cardiomyopathy With Severe Intercalated Disc Derangement in Humans and in Knock-In Mice
Authors: Herrmann Harald , Cabet Eva , Chevalier Nicolas R. , Moosmann Julia , Schultheis Dorothea , Haas Jan , Schowalter Mirjam , Berwanger Carolin , Weyerer Veronika , Agaimy Abbas , Meder Benjamin , Müller Oliver J. , Katus Hugo A. , Schlötzer-Schrehardt Ursula , Vicart Patrick , Ferreiro Ana , Dittrich Sven , Clemen Christoph S. , Lilienbaum Alain , Schröder Rolf
Published: October 2020

Background:

Mutations in the human desmin gene cause myopathies and cardiomyopathies. This study aimed to elucidate molecular mechanisms initiated by the heterozygous R406W-desmin mutation in the development of a severe and early-onset cardiac phenotype.

Methods:

We report an adolescent patient who underwent cardiac transplantation as a result of restrictive cardiomyopathy caused by a heterozygous R406W-desmin mutation. Sections of the explanted heart were analyzed with antibodies specific to 406W-desmin and to intercalated disc proteins. Effects of the R406W mutation on the molecular properties of desmin were addressed by cell transfection and in vitro assembly experiments. To prove the genuine deleterious effect of the mutation on heart tissue, we further generated and analyzed R405W-desmin knock-in mice harboring the orthologous form of the human R406W-desmin.

Results:

Microscopic analysis of the explanted heart revealed desmin aggregates and the absence of desmin filaments at intercalated discs. Structural changes within intercalated discs were revealed by the abnormal organization of desmoplakin, plectin, N-cadherin, and connexin-43. Next-generation sequencing confirmed the
DES
variant c.1216C>T (p.R406W) as the sole disease-causing mutation. Cell transfection studies disclosed a dual behavior of R406W-desmin with both its integration into the endogenous intermediate filament system and segregation into protein aggregates. In vitro, R406W-desmin formed unusually thick filaments that organized into complex filament aggregates and fibrillar sheets. In contrast, assembly of equimolar mixtures of mutant and wild-type desmin generated chimeric filaments of seemingly normal morphology but with occasional prominent irregularities. Heterozygous and homozygous R405W-desmin knock-in mice develop both a myopathy and a cardiomyopathy. In particular, the main histopathologic results from the patient are recapitulated in the hearts from R405W-desmin knock-in mice of both genotypes. Moreover, whereas heterozygous knock-in mice have a normal life span, homozygous animals die at 3 months of age because of a smooth muscle-related gastrointestinal phenotype.

Conclusions:

We demonstrate that R406W-desmin provokes its severe cardiotoxic potential by a novel pathomechanism, where the concurrent dual functional states of mutant desmin assembly complexes underlie the uncoupling of desmin filaments from intercalated discs and their structural disorganization.
Coordination and Consonance Between Interacting, Improvising Musicians
Authors: Setzler Matthew , Goldstone Robert
Published: October 2020

Joint action (JA) is ubiquitous in our cognitive lives. From basketball teams to teams of surgeons, humans often coordinate with one another to achieve some common goal. Idealized laboratory studies of group behavior have begun to elucidate basic JA mechanisms, but little is understood about how these mechanisms scale up in more sophisticated and open-ended JA that occurs in the wild. We address this gap by examining coordination in a paragon domain for creative joint expression: improvising jazz musicians. Coordination in jazz music subserves an aesthetic goal: the generation of a collective musical expression comprising coherent, highly nuanced musical structure (e.g., rhythm, harmony). In our study, dyads of professional jazz pianists improvised in a “coupled,” mutually adaptive condition, and an “overdubbed” condition that precluded mutual adaptation, as occurs in common studio recording practices. Using a model of musical tonality, we quantify the flow of rhythmic and harmonic information between musicians as a function of interaction condition. Our analyses show that mutually adapting dyads achieve greater temporal alignment and produce more consonant harmonies. These musical signatures of coordination were preferred by independent improvisers and naive listeners, who gave higher quality ratings to coupled interactions despite being blind to condition. We present these results and discuss their implications for music technology and JA research more generally.
Interactive Worksheets for Teaching Atmospheric Aerosols and Cloud Physics
Authors: Petters Markus
Published: October 2020

Student-centered active learning pedagogies improve learning outcomes and increase the engagement of underrepresented groups. Implementing such pedagogies requires interactive tools for students to manipulate inputs and use the outputs to construct knowledge. This work introduces interactive worksheets for teaching about atmospheric aerosol and cloud physics and describes the toolchain to create and deliver the content. The material is appropriate for upper-level undergraduate and graduate instruction with pedagogy based on process-oriented guided inquiry learning. Students playfully interact with physical relationships and atmospheric models. Two examples are the interaction with an aerosol–cloud parcel model for simulating the early stage of cloud formation and the interaction with the Bowen model for simulating the formation of rain by coalescence. Photos, text, figures, and software associated with the project are free to be shared and free to be adapted. In addition to focusing on discipline-based learning objectives, the worksheets emphasize interacting with real-world data and practicing graph comprehension. Hosting the content in the cloud ensures reliable and scalable delivery to any device with a browser and Internet access. The worksheets are designed to be used in a student-centered active learning classroom but can also be used in an online setting.