bluuebunny/crossref_metadata_2025 huggingface dataset:
Rare germline genetic variants and risk of aggressive prostate cancer
Authors: Nguyen‐Dumont Tú , MacInnis Robert J. , Steen Jason A. , Theys Derrick , Tsimiklis Helen , Hammet Fleur , Mahmoodi Maryam , Pope Bernard J. , Park Daniel J. , Mahmood Khalid , Severi Gianluca , Bolton Damien , Milne Roger L. , Giles Graham G. , Southey Melissa C.
Published: April 2020

Few genetic risk factors have been demonstrated to be specifically associated with aggressive prostate cancer (PrCa). Here, we report a case‐case study of PrCa comparing the prevalence of germline pathogenic/likely pathogenic (P/LP) genetic variants in 787 men with aggressive disease and 769 with nonaggressive disease. Overall, we observed P/LP variants in 11.4% of men with aggressive PrCa and 9.8% of men with nonaggressive PrCa (two‐tailed Fisher's exact tests, P = .28). The proportion of BRCA2 and ATM P/LP variant carriers in men with aggressive PrCa exceeded that observed in men with nonaggressive PrCa; 18/787 carriers (2.3%) and 4/769 carriers (0.5%), P = .004, and 14/787 carriers (0.02%) and 5/769 carriers (0.01%), P = .06, respectively. Our findings contribute to the extensive international effort to interpret the genetic variation identified in genes included on gene‐panel tests, for which there is currently an insufficient evidence‐base for clinical translation in the context of PrCa risk.
Phase III randomized, double‐blind study of paclitaxel with and without everolimus in patients with advanced gastric or esophagogastric junction carcinoma who have progressed after therapy with a fluoropyrimidine/platinum‐containing regimen (RADPAC)
Authors: Lorenzen Sylvie , Knorrenschild Jorge Riera , Pauligk Claudia , Hegewisch‐Becker Susanna , Seraphin Jörg , Thuss‐Patience Peter , Kopp Hans‐Georg , Dechow Tobias , Vogel Arndt , Luley Kim Barbara , Pink Daniel , Stahl Michael , Kullmann Frank , Hebart Holger , Siveke Jens , Egger Matthias , Homann Nils , Probst Stephan , Goetze Thorsten Oliver , Al‐Batran Salah‐Eddin
Published: April 2020

The RADPAC trial evaluated paclitaxel with everolimus in patients with advanced gastroesophageal cancer (GEC) who have progressed after therapy with a fluoropyrimidine/platinum‐containing regimen. Patients were randomly assigned to receive paclitaxel (80 mg/m2) on day 1, 8 and 15 plus everolimus (10 mg daily, arm B) d1‐d28 or placebo (arm A), repeated every 28 days. Primary end point was overall survival (OS). Efficacy was assessed in the intention‐to‐treat population and safety in all patients who received at least one dose of treatment. This trial is registered with ClinicalTrials.gov, number NCT01248403. Between October 2011 and September 2015, 300 patients (median age: 62 years; median lines prior therapy: 2; 47.7% of patients had prior taxane therapy) were randomly assigned (arm A, 150, arm B, 150). In the intention to treat population, there was no significant difference in progression‐free survival (PFS; everolimus, 2.2 vs placebo, 2.07 months, HR 0.88, P = .3) or OS (everolimus, 6.1 vs placebo, 5.0 months, HR 0.93, P = .54). For patients with prior taxane use, everolimus improved PFS (everolimus, 2.7 vs placebo 1.8 months, HR 0.69, P = .03) and OS (everolimus, 5.8 vs placebo 3.9 months, HR 0.73, P = .07). Combination of paclitaxel and everolimus was associated with significantly more grade 3‐5 mucositis (13.3% vs 0.7%; P < .001). The addition of everolimus to paclitaxel did not improve outcomes in pretreated metastatic gastric/gastroesophageal junction (GEJ) cancer. Activity was seen in the taxane pretreated group. Additional biomarker studies are planned to look for subgroups that may have a benefit.
Characterization of Pre‐Dissociative Structures of the E6AP Trimer by All‐atom Unbiased Molecular Dynamics
Authors: Chaturvedi Navaneet , Nachliel Esther , Gutman Menachem
Published: April 2020

The activity of the E6AP protein, a member of the ubiquitin transfer system, is regulated through the association‐dissociation of its homo‐trimeric structure. Under physiologic conditions, this protein is in a mixture of mono, di and tri‐mere complexes, where the D543A mutation further destabilize the complex. These featured render this protein as an excellent model for a study of pre‐dissociation events that can be detected by applying a cluster analysis of the ∼200 ns long trajectories. The analysis of the WT complex revealed inherent divergence of the subunits, each exhibiting multiplicity of configurations that differ in their energy. Surprisingly, the trimer is more stable than the subunits. The D543A mutation caused the trimer complex to assume many equi‐potential configurations, rendering it more flexible than the subunits. The trimeric destabilization is not observed in a mutant that affects only the structure of the active site. We propose that the pre‐dissociation configurations can be identified much earlier than the structural disintegration of a proteinous complex.
Literacy Coaching With Teachers of Adolescent English Learners: Agency, Sustainability, and Transformation for Equity
Authors: Reichenberg Jennifer Sharples
Published: April 2020

As literacy coaching grows in popularity and schools grow in diversity, it is important to explore approaches to support sustainable and transformative teacher learning in complex settings. This seven‐month case study of the author’s coaching with two teachers of English learners (ELs) in an urban high school illustrates the use of a reflective framework with video to support agentive, sustainable, transformative literacy coaching. The reflective framework, developed by the author, begins with teachers’ own perplexity about literacy teaching and learning. Dialogue from coaching sessions shows how the framework capitalized on differing expertise of the EL teacher and literacy coach, providing key entry points for both professionals into the reflective conversation. Although one teacher chose to explore a perceived strength and the other teacher chose to explore a perceived weakness, coaching with the framework led to agency, sustainability, and transformation in both teachers, including thinking and practices that empowered ELs to take ownership of their literacy learning.
Change point estimation in panel data with time‐varying individual effects
Authors: Boldea Otilia , Drepper Bettina , Gan Zhuojiong
Published: April 2020

Existing panel data methods remove unobserved individual effects before change point estimation through data transformations such as first‐differencing. In this paper, we show that multiple change points can be consistently estimated in short panels via ordinary least squares. Since no data variation is removed before change point estimation, our method has better small‐sample properties compared to first‐differencing methods. We also propose two tests that identify whether the change points found by our method originate in the slope parameters or in the covariance of the regressors with individual effects. We illustrate our method via modeling the environmental Kuznets curve and the US house price expectations after the financial crisis.
Changes in soil cadmium concentrations with time following cessation of phosphorus fertilizer inputs
Authors: Gray Colin William , McDowell Richard William , Condron Leo Murtagh , McLenaghen Roger David
Published: April 2020

Cadmium (Cd) can accumulate in soil from the application of phosphorus fertilizer. However, there is little information on what happens to soil Cd concentrations when Cd inputs stop. This study used soil and pasture samples collected from a long‐term field trial to measure changes in Cd concentrations in soil for 22 yr after Cd inputs from fertilizer had stopped and assessed whether the application of nitrogen (N) (50 kg ha−1 yr−1) could increase plant uptake of Cd and reduce soil Cd concentrations. It was found that there was no significant change in total or labile soil Cd (1 M CaCl2 extractable) concentrations after Cd inputs stopped. The application of N did not significantly (P < .05) increase dry matter yield or increase Cd solubility. As a result, N did not enhance plant uptake of Cd. A mass balance that included Cd loss via plant uptake and Cd leaching confirmed they were insufficient to result in a detectable decrease in soil Cd concentration over the 22‐yr interval of the trial. It appears that even an acid soil with low amounts of carbon (2.67%), iron/aluminum oxides, and clay can still strongly retain Cd, preventing Cd depletion from the soil, despite stopping Cd inputs and trying to enhance plant uptake of Cd from the application of N fertilizer.
Climate change projections and extremes for Costa Rica using tailored predictors from CORDEX model output through statistical downscaling with artificial neural networks
Authors: Quesada‐Chacón Dánnell , Barfus Klemens , Bernhofer Christian
Published: April 2020

Despite intense research on climate change (CC), regional studies for Central America, which is considered a CC hot spot, remain scarce. The information provided by general circulation models (GCMs) is too coarse to accurately reproduce local‐scale climatic features, which are needed for impact assessment. Thus, downscaling techniques are employed to address this scale mismatch. Costa Rica is the present case study, for which suitable predictors were tailored for downscaling related to regional climatic characteristics, such as the Inter‐Tropical Convergence Zone, El Niño Southern Oscillation, the Caribbean Low‐Level Jet, and the Mid‐Summer Drought. Statistical downscaling models were calibrated for precipitation, maximum and minimum temperature, using the perfect prognosis methodology by means of station data, ERA‐INTERIM reanalysis and artificial neural networks, yielding satisfactory results. As found in several studies, the temperature models replicated more accurately the statistics of the observed datasets. However, here, through the implemented approach and the tailored predictors, the precipitation models conveyed an improvement compared to standard methods. Projected daily climate was obtained employing CORDEX data under the RCP8.5 scenario for the central region of the country. Overall, the changes in climate estimated by the end of the 21st century agree with coarser‐scale projections. Finally, projected climate extremes indices were calculated and rendered further details on the intensity of future CC by the end of the century.
Distinct temperature behavior of the local structure of (1‐x)PbTiO3‐xBiNi0.5Ti0.5O3 at the morphotropic phase boundary
Authors: Margaritescu Irina , Datta Kaustuv , Chen Jun , Mihailova Boriana
Published: April 2020

Temperature‐dependent Raman spectroscopy was used to study the composition‐ and temperature‐driven structural transformations in the (1‐x)PbTiO3‐xBiNi0.5Ti0.5O3 solid solution, exhibiting a morphotropic phase boundary (MPB) at xMPB∼0.55 and a relatively high Curie temperature (TC∼680 K at xMPB). The analyses were carried out on ceramic samples, covering a wide temperature range across TC (100–1100 K) and several compositions across xMPB (0–0.70). The results reveal the presence of local ferroic distortions in the paraelectric phase of all compounds and strong composition‐induced enhancement of the order‐disorder phenomena across the para‐to‐ferroelelctric phase transition. The MPB compound is distinct by the absence of any temperature dependence of the wavenumber of the lowest‐energy A‐cation vibrational mode as well as by an equal dynamical weight of BO6 octahedral distortions and tilts below TC. The former indicates that at the MPB, the local‐scale structural polarity associated with the A site is purely composition‐driven, while the latter reveals competing local‐scale polar and antiferodistortive orders related to the B‐site sublattice in the ferroelectric state, which do not vanish but become energetically indistinguishable in the paraelectric state.
Size development of tomatoes growing in trusses: linking time of fruit set to diameter
Authors: Tijskens L M M , van Mourik S , Dieleman J A , Schouten R E
Published: April 2020

BACKGROUND

Size of fruit is an important issue in determining yield at harvest. Even under controlled conditions, variation between fruit and trusses can be considerable. As an easy to measure indication of size, the diameter of tomatoes growing in trusses was assessed in three experiments with different number of tomatoes per truss, as well as cultivars, and also by varying the level of ions in the recirculated drain water.

RESULTS

By applying the von Bertalanffy growth model, more than 99% of the variation present could be explained by the time of fruit set for all tomatoes growing anywhere in the trusses. A linear relationship between time of fruit set and the biological shift factor, an indication of developmental age, was observed. Integrating this linear relationship in the analysis of the diameter data removed one stochastic variable (biological shift factor), effectively halving the number of parameters to be estimated.

CONCLUSION

The results of the present study indicate that the major part of the variation present in the diameter of tomatoes growing in trusses is the result of variation in the time of fruit set of individual fruits. The position within the greenhouse (i.e. local differences in assimilates supply) exerted only a minor effect on diameter development. Accordingly, the time of fruit set largely determines fruit size. Likely, growing conditions before fruit set are crucial for final fruit size. The time of fruit set of each tomato in the truss and the local growing conditions within the greenhouse that affect assimilate supply need to be assessed accurately for a reliable size prediction.
Probabilistic assessment of the daily intake of microelements and toxic elements via the consumption of rice with different degrees of polishing
Authors: Hensawang Supanad , Lee Byung‐Tae , Kim Kyoung‐Woong , Chanpiwat Penradee
Published: April 2020

BACKGROUND

The polishing process plays a key role in determining the beneficial quality of rice. However, the effects of polishing on human exposure to essential and toxic elements are not well reported. This study evaluated the effects of polishing on the levels of essential and toxic elements in rice grains and evaluated the status of their daily intake using probabilistic assessment.

RESULTS

The levels of essential elements decreased as the degree of polishing increased. The highest reduction percentages of essential elements [24% of copper (Cu), 26% of nickel (Ni), and 52% of manganese (Mn)] were found after the first polishing step. The highest zinc (Zn) reduction (15%) was found after the fourth polishing step. For toxic elements, polishing significantly reduced the arsenic (As) concentration (15–31%) from that of the whole grains, of which 26% was removed after the first step.

CONCLUSION

Polishing removed both essential and toxic elements from rice grains. The highest losses of Cu, Mn, Ni, and As were found after the first polishing step since these elements generally localize in the aleurone layers of rice grains. The last polishing step caused a significant Zn reduction from the grain. Polishing had no significant effect on the cadmium (Cd) concentration in grains. The consumption of all types of rice could not supply sufficient amounts of all microelements except Mn to maintain optimum health. Both As and Cd intake levels were lower than the benchmarks of toxic health effects. Thus, the potential health impacts of both of these elements in rice can be neglected. © 2020 Society of Chemical Industry
Bacillus mycoides A1 and Bacillus tequilensisA3 inhibit the growth of a member of the phytopathogen Colletotrichum gloeosporioides species complex in avocado
Authors: Guerrero‐Barajas Claudia , Constantino‐Salinas Erick A , Amora‐Lazcano Enriqueta , Tlalapango‐Ángeles Daniel , Mendoza‐Figueroa José S , Cruz‐Maya Juan A , Jan‐Roblero Janet
Published: April 2020

BACKGROUND

Avocado is affected by Colletotrichum gloeosporioides causing anthracnose. Antagonistic microorganisms against C. gloeosporioides represent an alternative for biological control. Accordingly, in the present study, we focused on the isolation and characterization of potential antagonist bacteria against a member of the C. gloeosporioides species complex with respect to their possible future application.

RESULTS

Samples of avocado rhizospheric soil were aquired from an orchard located in Ocuituco, Morelos, Mexico, aiming to obtain bacterial isolates with potential antifungal activity. From the soil samples, 136 bacteria were isolated and they were then challenged against a member of the C. gloeosporioides species complex; only three bacterial isolates A1, A2 and A3 significantly diminished mycelial fungal growth by 75%, 70% and 60%, respectively. Two of these isolates were identified by 16S rRNA as Bacillus mycoides (A1 and A2) and the third was identified as Bacillus tequilensis (A3). Bacillus mycoides bacterial cell‐free supernatant reduced the mycelial growth of a member of the C. gloeosporioides species complex isolated from avocado by 65%, whereas Bacillus tequilensis A3 supernatant did so by 25% after 3 days post inoculation. Bacillus tequilensis mycoides A1 was a producer of proteases, indolacetic acid and siderophores. Preventive treatment using a cell‐free supernatant of B. mycoides A1 diminished the severity of anthracnose disease (41.9%) on avocado fruit.

CONCLUSION

These results reveal the possibility of using B. mycoides A1 as a potential biological control agent. © 2020 Society of Chemical Industry
The Role of Impulsivity in the Association Between Posttraumatic Stress Disorder Symptom Severity and Substance Use in Male Military Veterans
Authors: Mahoney Colin T. , Cole Hannah E. , Gilbar Ohad , Taft Casey T.
Published: April 2020

High rates of posttraumatic stress disorder (PTSD) and comorbid substance use disorder (SUD) are prevalent in military veterans. However, few studies have investigated impulsivity as a risk factor for engaging in substance use behavior for individuals who are experiencing PTSD symptoms. The present study evaluated impulsivity as a moderator of the association between PTSD symptoms and alcohol/drug use. Male military veterans (N = 106) completed self‐report measures of alcohol use behavior, drug use behavior, and impulsivity. Participants also completed a structured diagnostic interview to assess for PTSD. The findings indicated that impulsivity moderated the relation between total PTSD symptoms and alcohol use, B = 0.01, p = .035, along with associations between alcohol use and two of the symptom clusters: PTSD reexperiencing symptoms, B = 0.01, p = .016; and PTSD avoidance/numbing symptoms, B = 0.01, p = .029. Veterans with high levels of impulsivity were at significantly higher risk of engaging in alcohol use than veterans with low‐to‐average levels. Impulsivity did not potentiate the relation between PTSD hyperarousal symptoms and alcohol use nor did it moderate the association between any of the PTSD variables and drug use. Impulsivity appears to serve as a significant risk factor for alcohol use, but not drug use, for male veterans experiencing PTSD symptoms. Future studies are necessary to replicate and expand upon these findings, particularly to facilitate the development of integrated evidence‐based treatments that target both alcohol use and impulsivity within the context of PTSD.
Single‐Layer Aberration‐Compensated Flat Lens for Robust Wide‐Angle Imaging
Authors: Hao Chenglong , Gao Shecheng , Ruan Qifeng , Feng Yuanhua , Li Ying , Yang Joel K.W. , Li Zhaohui , Qiu Cheng‐Wei
Published: April 2020

Metasurfaces are planarized and miniaturized versions of conventional optical elements. Subwavelength‐thick single‐layer metalenses have diffraction limited resolution for on‐axis imaging but relatively low resolution for off‐axis imaging due to off‐axial aberrations. The aberrations of planar single‐layer metalenses have been corrected by patterning two metasurfaces on both sides of a substrate to form metalens doublets with a thickness of hundreds of micrometers to millimeters. The multilevel diffractive lenses are demonstrated to achieve wide angle imaging with a thickness of several micrometers, however, the off‐axial aberrations are not compensated. Here, an epsilon‐greedy algorithm‐based scheme for achieving a planar wavelength‐thick single‐layer aberration‐compensated (SLAC) flat lens consisting of dielectric nanoring structures fabricated by 3D printing are proposed. The scheme is experimentally validated via a SLAC flat lens. This SLAC flat lens has a thickness of 1 µm, a numerical aperture of 0.45, a focal length of 1 mm, a full field of view (FOV) of 32° that enables aberration‐compensated imaging along the focal plane and monochromatic microscopic imaging with resolution better than 2.2 µm at a wavelength of 633 nm. This scheme can lead to ultrathin wide‐FOV flat lens designs as well as low‐cost mass production, which has various applications in miniscopes, mobile camera modules, and machine vision.
Self‐Adhesive Microneedles with Interlocking Features for Sustained Ocular Drug Delivery
Authors: Amer Maher , Chen Roland K.
Published: April 2020

The interests in sustained ocular drug delivery have grown rapidly in recent years, with hope to replace repeated intravitreal injections. Microneedles (MNs), which are minimally invasive, have been shown to be a feasible vehicle for sustained drug delivery. However, securing an MN patch in the eye remains challenging. In this study, a new design of hydrogel MNs with interlocking features to achieve self‐adhesion is proposed. Upon swelling, the swollen interlocking features help secure the MNs in place. A new molding process is developed to fabricate MNs with interlocking features that can cause issues when demolding using the regular micromolding process. MNs with two different interlocking feature designs are used in this study and are made with polyvinyl alcohol. MNs with the interlocking features show an 80% increase in adhesion strength and a small amount of increase in penetration force, in comparison to MNs without any feature. The experiments are performed using both a sclera‐mimicking phantom and ex vivo eyes harvested from rabbits and are shown to have comparable results. This study demonstrates the feasibility of incorporating interlocking features to MNs to achieve self‐adhesion that can enable sustained drug delivery via MNs.
Lattice points in bodies of revolution II
Authors: Chamizo Fernando , Pastor Carlos
Published: April 2020

In [3] it was shown that when a three‐dimensional smooth convex body has rotational symmetry around a coordinate axis one can find better bounds for the lattice point discrepancy than what is known for more general convex bodies. To accomplish this, however, it was necessary to assume a non‐vanishing condition on the third derivative of the generatrix. In this article we drop this condition, showing that the aforementioned bound holds for a wider family of revolution bodies, which includes those with analytic boundary. A novelty in our approach is that, besides the usual analytic methods, it requires studying some Diophantine properties of the Taylor coefficients of the phase on the Fourier transform side.
Application of Genetic Algorithm in Simultaneous Deconvolution: Case Studies of Ethylene/1‐Butene Copolymers with Direct and Inverse MW/CC Relationships
Authors: Khayanying Kett , Anantawaraskul Siripon
Published: April 2020

For multiple‐site‐type catalytic system, simultaneous deconvolution of molecular weight distribution and chemical composition distribution can be used to determine the number of site types and chain microstructures of polymers produced on each site type. In the conventional deconvolution with generalized reduced gradient (GRG) nonlinear algorithm, appropriate initial guesses are often required. In the case that the relationship between molecular weight and comonomer content (MW/CC) is not known, inadequate initial guesses can lead to inaccurate parameter estimation. In this work, genetic algorithm is considered as an alternative optimization tool during simultaneous deconvolution with the advantage that it can reach the global solution without relying on the adequate initial guesses. The proposed approach is validated with simulated data of model ethylene/1‐butene copolymers with inverse and direct MW/CC relationships and benchmarked with the conventional GRG technique.
Developing Structure–Process–Property Relationships Using Multivariate Analysis
Authors: Fiscus David M.
Published: April 2020

The properties of polymeric materials depend on their composition, resin molecular architecture, and fabrication conditions, all of which have been related by reaction engineering, polymer science, and resin processing theories. However, gaps in these theories limit their use, particularly in developing new resins with superior performance. Mulitvariate statistics can remove these limitations and unravel the relationships between variables. These methods are used to establish the structure–process–property relationships of commercial polyethylene blown film resins. The results are used to develop new resins with unique and superior balances of properties. Suggestions on how to apply the results to other blown film problems are provided, such as, adapting processing conditions to accommodate resin variation and resin scale‐up operations. The methodology can be applied to other materials and applications. Key concepts are explained and developed using chemometrics.
Intraindividual Neurofilament Dynamics in Serum Mark the Conversion to Sporadic Parkinson's Disease
Authors: Wilke Carlo , dos Santos Marcia Cristina Teixeira , Schulte Claudia , Deuschle Christian , Scheller Dieter , Verbelen Moira , Brockmann Kathrin , von Thaler Anna‐Katharina , Sünkel Ulrike , Roeben Benjamin , Bujac Sarah , Metzger Florian G. , Maetzler Walter , da Costa Andre Nogueira , Synofzik Matthis , Berg Daniela
Published: April 2020

Background and Objectives

With disease‐modifying treatment strategies on the horizon, stratification of individual patients at the earliest stages of Parkinson's disease (PD) is key—ideally already at clinical disease onset. Blood levels of neurofilament light chain (NfL) provide an easily accessible fluid biomarker that might allow capturing the conversion from prodromal to manifest PD.

Methods

We assessed longitudinal serum NfL levels in subjects converting from prodromal to manifest sporadic PD (converters), at‐risk subjects, and matched controls (72 participants with ≈4 visits), using single‐molecule array (Simoa) technique.

Results

While NfL levels were not increased at the prodromal stage, subjects converting to the manifest motor stage showed a significant intraindividual acceleration of the age‐dependent increase of NfL levels.

Conclusions

The temporal dynamics of intraindividual NfL blood levels might mark the conversion to clinically manifest PD, providing a potential stratification biomarker for individual disease onset in the advent of precision medicine for PD. © 2020 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.
Panel‐based targeted exome sequencing reveals novel candidate susceptibility loci for age‐related cataracts in Chinese Cohort
Authors: Li Jian-Kang , Li Li‐Li , Li Wei , Wang Zi‐Wei , Gao Feng‐Juan , Hu Fang-Yuan , Zhang Sheng‐Hai , Qu Shou-Fang , Huang Jie , Wang Lu-Sheng , Wu Ji-Hong , Chen Fang
Published: April 2020

Background

Age‐related cataracts (ARC) is the most common blinding eye disease worldwide, and its incidence tend to become younger. However, the relationship between genetic factors and mechanisms is not fully understood. The aim of the study was to further clarify the relationship between ARC and genetic mechanisms in East Asian populations and to elucidate the pathogenesis.

Methods

The study collected 191 sporadic cataracts and 208 healthy people from the eastern provinces of China, with an average age of about 60 years. All participants were subjected to a comprehensive ophthalmic clinical examination and peripheral blood samples were collected and their genomic DNA was extracted. Mutations were screened among 792 candidate genes to enhance understanding of the disease through targeted capture and high‐throughput sequencing.

Results

We identified novel candidate susceptibility gene, which may serve as a potential susceptibility factor leading to an increase in the incidence of age‐related cataracts. Three novel loci are associated with age‐related cataracts significant significance: rs129882 in DBH (p = 5.27E‐07, odds ratio = 3.9), rs1800280 in DMD (p = 2.85E‐06, odds ratio = 1.4) and rs2871776 in ATP13A2 (p = 4.18E‐05, odds ratio = 0.04). Gene–gene interaction analysis revealed that the most significant interactions between genes include the interaction between DBH and TUB (rs17847537 in TUB, rs129882 in DBH, p‐value = 2.12E‐14), and the interaction between DBH and DMD (rs1800280 in DMD, rs129882 in DBH, p‐value = 2.12E‐14). Pathway analysis shows that the most significant processes are concentrated in response to light stimulation (adjusted p‐Value = 5.56E‐03), response to radiation (adjusted P‐Value = 5.56E‐03), abiotic stimulus (adjusted p‐Value = 5.56E‐03). eQTL analysis shows that DBH rs129882 could regulate the expression of DBH mRNA in various tissues including retina.

Conclusion

Our study indicates rs129882 and rs1800280 loci are associated with age‐related cataracts, which enlarge the gene map of age‐related cataracts.
Analyzing the dynamics of a stochastic rumor propagation model incorporating media coverage
Authors: Huo Liang'an , Dong Yafang
Published: April 2020

In the age of information globalization, research on the mechanism of propagation will help mitigate the bad influence of rumors. Based on the classical rumor propagation model, this paper further analyzes the internal mechanism of the stochastic rumor propagation model incorporating media coverage with white noise. We investigate the existence of a unique global positive solution to the model and study the dynamic properties of the solutions around the rumor‐free and local equilibrium points of the deterministic model. Furthermore, we establish sufficient conditions for the existence of traversal static distribution in the model. Numerical simulation shows that the role of media coverage is crucial to reduce the rumor propagation scale. The larger the coverage rate is, the smaller the rumor propagation scale is.
Defining Hausdorff operators on Euclidean spaces
Authors: Karapetyants Alexey , Liflyand Elijah
Published: April 2020

After 2000, an interest in the Hausdorff operators grew, first of all in the sense of a diversity of spaces on which these operators were considered. We try to introduce a ‘correct’ definition of the Hausdorff operator on Euclidean spaces. This is supplemented by a variety of known and possible applications.
Global dynamics of Filippov‐type plant disease models with an interaction ratio threshold
Authors: Li Wenxiu , Huang Lihong , Wang Jiafu
Published: April 2020

A Filippov‐type plant disease model is developed by introducing a interaction ratio threshold, the number of susceptible plants infected by per diseased plant, which determines whether control measures including replanting or roguing are carried out. The main purpose of this paper is to give a completely qualitative analysis of the model. By employing Poincaré maps, our analysis reveals rich dynamics including a global attractor bounded by a touching closed orbit, which is convergent in finite time from its outside, a global attractor bounded by two touching closed orbits and a pseudo‐saddle, and a globally asymptotically stable pseudo‐node. Moreover, we give biological implications of our results in implementing control strategies for plant diseases.
Approximate analytical solution of two‐dimensional space‐time fractional diffusion equation
Authors: Pandey Prashant , Kumar Sachin , Gómez Francisco
Published: April 2020

This work presents an iterative scheme for the numerical solution of the space‐time fractional two‐dimensional advection–reaction–diffusion equation applying homotopy perturbation with Laplace transform using Caputo fractional‐order derivatives. The solution obtained is beneficial and significant to analyze the modeling of superdiffusive systems and subdiffusive system, anomalous diffusion, transport process in porous media. This iterative technique presents the combination of homotopy perturbation technique, and Laplace transforms with He's polynomials, which can further be applied to numerous linear/nonlinear two‐dimensional fractional models to computes the approximate analytical solution. In the present method, the nonlinearity can be tackle by He's polynomials. The salient features of the present scientific work are the pictorial presentations of the approximate numerical solution of the two‐dimensional fractional advection–reaction–diffusion equation for different particular cases of fractional order and showcasing of the damping effect of reaction terms on the nature of probability density function of the considered two‐dimensional nonlinear mathematical models for various situations.
Exact and approximate solutions of time‐fractional models arising from physics via Shehu transform
Authors: Akinyemi Lanre , Iyiola Olaniyi S.
Published: April 2020

In this present investigation, we proposed a reliable and new algorithm for solving time‐fractional differential models arising from physics and engineering. This algorithm employs the Shehu transform method, and then nonlinearity term is decomposed. We apply the algorithm to solve many models of practical importance and the outcomes show that the method is efficient, precise, and easy to use. Closed form solutions are obtained in many cases, and exact solutions are obtained in some special cases. Furthermore, solution profiles are presented to show the behavior of the obtained results in other to better understand the effect of the fractional order.
An investigation into the robustness of dynamically collimated proton therapy treatments
Authors: Smith Blake R. , Hyer Daniel E. , Culberson Wesley S.
Published: April 2020

Purpose

To investigate the dosimetric robustness of dynamically collimated proton therapy (DCPT) treatment plans delivered using a dynamic collimation system (DCS) with respect to random uncertainties in beam spot and collimator position as well as systematic offsets in the DCS mounting alignment. This work also demonstrates a technique that can increase plan robustness while preserving target conformity.

Methods

Variability in beam spot and collimator positioning can result in changes to a beamlet's dose distribution and incident fluence. The robustness of the DCPT treatment plans was evaluated for three intracranial treatment sites by modeling treatment variability as normally distributed random variables with standard deviations reflecting a clinical system. The simulated treatment plans were then recalculated and compared against their nominal, idealized dose distribution among several trials. It was hypothesized that a plan's robustness to these delivery variables could be reduced by restricting a trimmer's placement toward a beamlet's central axis during collimation.

Results

By introducing a minimum trimmer offset of 1.5 mm, the variation of the planning target volume (PTV) D95% coverage was reduced to within 2% of the prescribed dose. The treatment plans with trimmers that were placed within 0.5 mm of a collimated beamlet's central axis resulted in the greatest healthy tissue sparing but deviations as high as 11.4% to the PTV D95% were observed. The nominal conformity of these treatment plans utilizing the 1.5 mm trimmer offset was also well maintained. For each treatment plan studied, the 90% conformity index remained within 6.25% of the conformity index achieved without a minimum trimmer offset, and the D50% of surrounding healthy tissue increased by no more than 3.1 Gy relative to a plan without a trimmer offset.

Conclusions

While DCPT can offer a significant reduction in healthy tissue irradiation, the results from this work indicate that special care must be taken to ensure proper PTV coverage amid uncertainties associated with this new treatment modality. A simple approach utilizing a minimum trimmer offset was able to preserve the majority of the target conformity and healthy tissue sparing the DCS technology affords while minimizing the uncertainties in this treatment approach.
Pharmacological characterization of a novel potent, selective, and orally active orexin 2 receptor antagonist, SDM‐878
Authors: Maehara Shunsuke , Yuge Natsuko , Higashi Chika , Ota Takumi , Furukawa Junji , Takeuchi Takashi
Published: April 2020

Aims

Recently, we identified a novel orexin 2 (OX2) receptor antagonist, SDM‐878 (2‐(3‐(2‐(1H‐pyrazol‐1‐yl)nicotinoyl)‐3,8‐diazabicyclo[3.2.1]octan‐8‐yl)‐3‐methoxyisonicotinonitrile). The purpose of the present study is to characterize the in vitro and in vivo pharmacological effects of SDM‐878.

Methods

The in vitro potency and selectivity of SDM‐878 were examined in CHO cells that exhibit stable expression of human orexin 1 (OX1), human orexin 2 (OX2), rat OX1, and rat OX2receptors. Then, the plasma half‐life, oral bioavailability, and brain penetration of SDM‐878 were examined in rats. The in vivo effect of SDM‐878 in rats was tested using electroencephalography (EEG). The target engagement of SDM‐878 in the rat brain was examined using the antagonistic effect against hyperlocomotion caused by the intracerebroventricular administration of the OX2 receptor agonist, ADL‐OXB ([Ala11, d‐Leu15]‐orexin B).

Results

SDM‐878 showed potent inhibitory activities for human and rat OX2 receptors with IC values of 10.6 and 8.8 nM, respectively, and approximately 1000‐fold selectivity against the OX1receptor. In rat studies, SDM‐878 exhibited a relatively short half‐life in plasma, oral bioavailability, and good brain penetration. These data indicate that SDM‐878 is a potent, selective, orally active, and brain‐penetrable OX2receptor antagonist. In behavioral studies using rats, SDM‐878 (100 mg/kg) antagonized hyperlocomotion caused by intracerebroventricular administration of ADL‐OXB. SDM‐878 exhibited a potent sleep‐promoting effect at the same dose (100 mg/kg) in a rat EEG study.

Conclusion

Our results suggest that SDM‐878 is likely to be a good pharmacological tool for investigating the role of the OX2receptor and may have therapeutic potential for the treatment of insomnia.
Effectiveness of fiscal incentives for innovation: Evidence from meta‐regression analysis
Authors: Jose Manu , Sharma Ruchi
Published: April 2020

This article examines the microeconometric evidence on the impact of government support for R&D and innovation. Our meta‐regression analysis uses a dataset of empirical evidence on the effects of government R&D policies on innovation and investigates the factors that may explain the differences in the estimated effects. The meta‐analysis is structured to include both the direct and indirect government support for R&D and innovation. The estimated results reveal the heterogeneity of empirical studies with respect to the type of incentive, data, and econometric methodology used. The results indicate that the output additionality effect is on average stronger for R&D tax incentives than subsidies. Studies that use the subsample of high technology sector show a stronger additionality effect of fiscal incentives on innovation. Moreover, small and medium enterprises have a stronger input additionality effect. The results also suggest that studies considered endogeneity issues have on average stronger additionality effect.
Modeling constituent–property relationship of polyvinylchloride composites by neural networks
Authors: Reddy Bhumi Reddy Srinivasulu , Premasudha Mookala , Panigrahi Bharat B. , Cho Kwon‐Koo , Reddy Nagireddy Gari Subba
Published: April 2020

The purpose of this study is to develop an artificial neural network (ANN) model to predict and analyze the relationship between properties and process parameters of polyvinyl chloride (PVC) composites. The tensile strength, ductility, and density of PVC are modeled as a function of virgin PVC, recycled PVC, CaCO3, di‐2‐ethylhexyl phthalate, chlorinated paraffin wax, and CaCO3 particle size. The ANN model is trained using the backpropagation algorithm. The developed model was validated with a set of unseen test data. The correlation coefficient adj. R2 values for test data were 0.95, 0.83, and 0.90 for tensile strength, density, and ductility, respectively. The relationship between constituents and properties of PVC composites were analyzed by sensitivity analysis, index of relative importance, and quantitative estimation. The study concluded that ANN modeling was a dependable tool for the optimization of constituents for the desired properties of PVCs.
Analysis of the isoprenoid pathway intermediates, dimethylallyl diphosphate and isopentenyl diphosphate, from crude plant extracts by liquid chromatography tandem mass spectrometry
Authors: Krause Toni , Reichelt Michael , Gershenzon Jonathan , Schmidt Axel
Published: April 2020

Objective

We sought to develop a sensitive and accurate analytical method for the detection and quantification of IDP and DMADP as well as their monophosphate derivatives in crude plant extracts.

Methods

A liquid chromatography method coupled to tandem mass spectrometry (LC–MS/MS) with multiple reaction monitoring (MRM) was established to measure the amounts of IDP and DMADP down to low picogram levels, which was linear over at least three orders of magnitude. Extracts were enriched using an anion exchanger, and chromatographic separation was achieved using a β‐cyclodextrin column. A S‐thiolodiphosphate analog of DMADP was employed as an internal standard.

Results

Dilution series of authentic compounds were used to determine the limits of detection and quantification for IDP, DMADP and their corresponding monophosphates. A survey of plant species producing varying amounts of isoprenoids showed a corresponding variation in IDP and DMADP with the ratio of DMADP/IDP ranging from 4:1 to 2:1. Trace levels of isopentenyl monophosphate (IP) and dimethylallyl monophosphate (DMAP) were also detected.

Conclusion

The LC–MS/MS method described enables absolute quantification of in planta levels of IDP and DMADP for the first time. The method is also suitable for analysing bacterial and animal samples as well as enzyme assays.
Managing COVID‐19 in Renal Transplant Recipients: A Review of Recent Literature and Case Supporting Corticosteroid‐sparing Immunosuppression
Authors: Johnson Kristen M. , Belfer Julie J. , Peterson Gina R. , Boelkins Mark R. , Dumkow Lisa E.
Published: April 2020

Novel coronavirus disease 2019 (COVID‐19) caused by severe acute respiratory syndrome virus (SARS‐CoV‐2) has become a global health care crisis. The Centers for Disease Control and Prevention (CDC) lists immunocompromised patients, including those requiring immunosuppression following renal transplantation, as high risk for severe disease from SARS‐CoV‐2. Treatment for other viral infections in renal transplant recipients often includes a reduction in immunosuppression; however, no current guidelines are available recommending the optimal approach to managing immunosuppression in the patients who are infected with SARS‐CoV‐2. It is currently advised to avoid corticosteroids in the treatment of SARS‐CoV‐2 outside of critically ill patients. Recently published cases describing inpatient care of COVID‐19 in renal transplant recipients differ widely in disease severity, time from transplantation, baseline immunosuppressive therapy, and the modifications made to immunosuppression during COVID‐19 treatment. This review summarizes and compares inpatient immunosuppressant management strategies of recently published reports in the renal transplant population infected with SARS‐CoV‐2 and discusses the limitations of corticosteroids in managing immunosuppression in this patient population.
Organic ferroelectric field‐effect transistor memories with poly(vinylidene fluoride) gate insulators and conjugated semiconductor channels: a review
Authors: Zhu Huie , Fu Chang , Mitsuishi Masaya
Published: April 2020

Organic electronics have attracted considerable interest because of their low temperature solution processability, versatile material synthesis and compatibility with a wide range of traditional fabrication methods such as rod‐coating, inkjet and roll‐to‐roll printing techniques. Organic ferroelectric field‐effect transistors (OFeFETs) with a three‐terminal device architecture have ferroelectric thin films as gate insulator layers and semiconductor films as charge transport channel layers. OFeFETs have been demonstrated with non‐volatile memory functions that can retain their high or low conductive states in the semiconductor channel when the power is turned off. The reversible polarization switching in the ferroelectric gate insulator layer between two stable polarized states provides the basis for binary coded memory functions. In this review, we summarize recent development of OFeFETs based on ferroelectric poly(vinylidene fluoride) dielectrics and organic semiconductor channels. © 2020 Society of Chemical Industry
Perils of perfectionistic concerns among teachers
Authors: Shim Serena , Cho YoonJung , Knapke Melissa
Published: April 2020

The current study examined how teachers’ perfectionism (personal standards [PS] and concern over mistakes [COM]) relates to their achievement goals for teaching, instructional practices (creation of mastery vs. performance classroom goal structures), job satisfaction, and flow experience during teaching. The data were collected from teachers (N = 143; mean age = 43.5; 70% female; 100% European American) practicing in the Midwestern U.S. Path analyses indicated that teachers’ high personal standards predicted endorsement of mastery goals for teaching, creation of mastery goal structure emphasizing personal progress and learning, high job satisfaction, and frequent flow experience during teaching. On the contrary, teachers’ high concern over mistakes predicted endorsement of performance‐approach and ‐avoidance goals, creation of classroom performance goal structure emphasizing competition among students, low job satisfaction, and infrequent flow experience during teaching. A significant interaction between PS and COM was found for fluency (subscale of flow) experience, indicating that PS can buffer the harmful effects of COM. Therefore, the study evidenced the benefits of PS and the drawbacks of COM.