bluuebunny/crossref_metadata_2025 huggingface dataset:
Metabolic Changes in Early-Stage Non–Small Cell Lung Cancer Patients after Surgical Resection
Authors: Ahmed Naseer , Kidane Biniam , Wang Le , Nugent Zoann , Moldovan Nataliya , McElrea April , Shariati-Ievari Shiva , Qing Gefei , Tan Lawrence , Buduhan Gordon , Srinathan Sadeesh K. , Aliani Michel
Published: June 2021

Metabolic alterations in malignant cells play a vital role in tumor initiation, proliferation, and metastasis. Biofluids from patients with non–small cell lung cancer (NSCLC) harbor metabolic biomarkers with potential clinical applications. In this study, we assessed the changes in the metabolic profile of patients with early-stage NSCLC using mass spectrometry and nuclear magnetic resonance spectroscopy before and after surgical resection. A single cohort of 35 patients provided a total of 29 and 32 pairs of urine and serum samples, respectively, pre-and post-surgery. We identified a profile of 48 metabolites that were significantly different pre- and post-surgery: 17 in urine and 31 in serum. A higher proportion of metabolites were upregulated than downregulated post-surgery (p < 0.01); however, the median fold change (FC) was higher for downregulated than upregulated metabolites (p < 0.05). Purines/pyrimidines and proteins had a larger dysregulation than other classes of metabolites (p < 0.05 for each class). Several of the dysregulated metabolites have been previously associated with cancer, including leucyl proline, asymmetric dimethylarginine, isopentenyladenine, fumaric acid (all downregulated post-surgery), as well as N6-methyladenosine and several deoxycholic acid moieties, which were upregulated post-surgery. This study establishes metabolomic analysis of biofluids as a path to non-invasive diagnostics, screening, and monitoring in NSCLC.
The CRISPR/Cas9 Minipig—A Transgenic Minipig to Produce Specific Mutations in Designated Tissues
Authors: Berthelsen Martin Fogtmann , Riedel Maria , Cai Huiqiang , Skaarup Søren H. , Alstrup Aage K. O. , Dagnæs-Hansen Frederik , Luo Yonglun , Jensen Uffe B. , Hager Henrik , Liu Ying , Callesen Henrik , Vendelbo Mikkel H. , Jakobsen Jannik E. , Thomsen Martin Kristian
Published: June 2021

The generation of large transgenic animals is impeded by complex cloning, long maturation and gastrulation times. An introduction of multiple gene alterations increases the complexity. We have cloned a transgenic Cas9 minipig to introduce multiple mutations by CRISPR in somatic cells. Transgenic Cas9 pigs were generated by somatic cell nuclear transfer and were backcrossed to Göttingen Minipigs for two generations. Cas9 expression was controlled by FlpO-mediated recombination and was visualized by translation from red to yellow fluorescent protein. In vitro analyses in primary fibroblasts, keratinocytes and lung epithelial cells confirmed the genetic alterations executed by the viral delivery of single guide RNAs (sgRNA) to the target cells. Moreover, multiple gene alterations could be introduced simultaneously in a cell by viral delivery of sgRNAs. Cells with loss of TP53, PTEN and gain-of-function mutation in KRASG12D showed increased proliferation, confirming a transformation of the primary cells. An in vivo activation of Cas9 expression could be induced by viral delivery to the skin. Overall, we have generated a minipig with conditional expression of Cas9, where multiple gene alterations can be introduced to somatic cells by viral delivery of sgRNA. The development of a transgenic Cas9 minipig facilitates the creation of complex pre-clinical models for cancer research.
Effects of Macro-/Micro-Channels on Vascularization and Immune Response of Tissue Engineering Scaffolds
Authors: Wen Nolan , Qian Enze , Kang Yunqing
Published: June 2021

Although the use of porous scaffolds in tissue engineering has been relatively successful, there are still many limitations that need to be addressed, such as low vascularization, low oxygen and nutrient levels, and immune-induced inflammation. As a result, the current porous scaffolds are insufficient when treating large defects. This paper analyzed scientific research pertaining to the effects of macro-/micro-channels on the cell recruitment, vascularization, and immune response of tissue engineering scaffolds. Most of the studies contained either cell culturing experimentation or experimentation on small animals such as rats and mice. The sacrificial template method, template casting method, and 3D printing method were the most common methods in the fabrication of channeled scaffolds. Some studies combine the sacrificial and 3D printing methods to design and create their scaffold with channels. The overall results from these studies showed that the incorporation of channels within scaffolds greatly increased vascularization, reduced immune response, and was much more beneficial for cell and growth factor recruitment compared with control groups that contained no channels. More research on the effect of micro-/macro-channels on vascularization or immune response in animal models is necessary in the future in order to achieve clinical translation.
TRIMming Down Hormone-Driven Cancers: The Biological Impact of TRIM Proteins on Tumor Development, Progression and Prognostication
Authors: Pauletto Eleonora , Eickhoff Nils , Padrão Nuno , Blattner Christine , Zwart Wilbert
Published: June 2021

The tripartite motif (TRIM) protein family is attracting increasing interest in oncology. As a protein family based on structure rather than function, a plethora of biological activities are described for TRIM proteins, which are implicated in multiple diseases including cancer. With hormone-driven cancers being among the leading causes of cancer-related death, TRIM proteins have been described to portrait tumor suppressive or oncogenic activities in these tumor types. This review describes the biological impact of TRIM proteins in relation to hormone receptor biology, as well as hormone-independent mechanisms that contribute to tumor cell biology in prostate, breast, ovarian and endometrial cancer. Furthermore, we point out common functions of TRIM proteins throughout the group of hormone-driven cancers. An improved understanding of the biological impact of TRIM proteins in cancer may pave the way for improved prognostication and novel therapeutics, ultimately improving cancer care for patients with hormone-driven cancers.
Trace Amine-Associated Receptor 1 Trafficking to Cilia of Thyroid Epithelial Cells
Authors: Qatato Maria , Venugopalan Vaishnavi , Al-Hashimi Alaa , Rehders Maren , Valentine Aaron D. , Hein Zeynep , Dallto Uillred , Springer Sebastian , Brix Klaudia
Published: June 2021

Trace amine-associated receptor 1 (rodent Taar1/human TAAR1) is a G protein-coupled receptor that is mainly recognized for its functions in neuromodulation. Previous in vitro studies suggested that Taar1 may signal from intracellular compartments. However, we have shown Taar1 to localize apically and on ciliary extensions in rodent thyrocytes, suggesting that at least in the thyroid, Taar1 may signal from the cilia at the apical plasma membrane domain of thyrocytes in situ, where it is exposed to the content of the follicle lumen containing putative Taar1 ligands. This study was designed to explore mouse Taar1 (mTaar1) trafficking, heterologously expressed in human and rat thyroid cell lines in order to establish an in vitro system in which Taar1 signaling from the cell surface can be studied in future. The results showed that chimeric mTaar1-EGFP traffics to the apical cell surface and localizes particularly to spherical structures of polarized thyroid cells, procilia, and primary cilia upon serum-starvation. Moreover, mTaar1-EGFP appears to form high molecular mass forms, possibly homodimers and tetramers, in stably expressing human thyroid cell lines. However, only monomeric mTaar1-EGFP was cell surface biotinylated in polarized human thyrocytes. In polarized rat thyrocytes, mTaar1-EGFP is retained in the endoplasmic reticulum, while cilia were reached by mTaar1-EGFP transiently co-expressed in combination with an HA-tagged construct of the related mTaar5. We conclude that Taar1 trafficking to cilia depends on their integrity. The results further suggest that an in vitro cell model was established that recapitulates Taar1 trafficking in thyrocytes in situ, in principle, and will enable studying Taar1 signaling in future, thus extending our general understanding of its potential significance for thyroid autoregulation.
Associations between Language at 2 Years and Literacy Skills at 7 Years in Preterm Children Born at Very Early Gestational Age and/or with Very Low Birth Weight
Authors: Joensuu Eveliina , Munck Petriina , Setänen Sirkku , Lipsanen Jari , Huhtala Mira , Lapinleimu Helena , Stolt Suvi K. J.
Published: June 2021

Preterm children (born <37 gestational weeks) who are born at very early gestational age (<32 weeks, very preterm, VP) and/or with very low birth weight (≤1500 g, VLBW) are at increased risk for language and literacy deficits. The continuum between very early language development and literacy skills among these children is not clear. Our objective was to investigate the associations between language development at 2 years (corrected age) and literacy skills at 7 years in VP/VLBW children. Participants were 136 VP/VLBW children and 137 term controls (a 6-year regional population cohort, children living in Finnish-speaking families). At 2 years of corrected age, language (lexical development, utterance length) was assessed using the Finnish version of the MacArthur–Bates Communicative Development Inventory and the Expressive Language Scale from Bayley scales of Infant Development, second edition. At 7 years, children’s literacy skills (pre-reading skills, reading, and writing) were evaluated. Statistically significant correlations were found in both groups between language development at 2 years and literacy skills at 7 years (r-values varied between 0.29 and 0.43, p < 0.01). In the VP/VLBW group, 33% to 74% of the children with early weak language development had weak literacy skills at 7 years relative to those with more advanced early language skills (11% to 44%, p < 0.001 to 0.047). Language development at 2 years explained 14% to 28% of the variance in literacy skills 5 years later. Language development at 2 years had fair predictive value for literacy skills at 7 years in the VP/VLBW group (area under the receiver operating characteristic (ROC) curve (AUC) values varied between 0.70 and 0.77, p < 0.001). Findings provide support for the continuum between very early language development and later language ability, in the domain of literacy skills in preterm children.
Tailoring Periodic Vertical Cracks in Thermal Barrier Coatings Enabling High Strain Tolerance
Authors: Mehboob Ghazanfar , Xu Tong , Li Guang-Rong , Yang Guan-Jun , Tahir Adnan , Ragab Mohamed , Hussain Shahnwaz
Published: June 2021

Lifetime is a basic support for the thermal insulation function of thermal barrier coatings (TBCs). Therefore, extending the life span is essential to develop next-generation TBCs. For this objective, the columnar structure formed by vertical cracks appears to make sense. However, the underlying mechanism is still unclear. This work scrutinizes the influence of periodic vertical cracks on cracking behavior in order to tailor high strain tolerant TBCs. A finite element model was evolved to explore the crack behavior influenced by thermal mismatch strain between substrate and coating. The virtual crack closure technique (VCCT) was used to describe the propagation of crack under load. It is found clearly that the space between two vertical cracks (short for SVC) along the in-plane direction has a noteworthy influence on the strain tolerance of TBCs. Results indicate that the strain energy release rate (SERR) and stresses at the pre-crack tip increase continuously with the increase of the SVC, suggesting that the driving force for cracks is increasing. The crack is not propagated when the SVC is very small, whereas the crack grows continuously with the increase of the SVC. The growth of a crack can be prevented by reducing the SVC. A critical value for the SVC was found. When the SVC is less than the critical value, the SERR can be dramatically reduced. Thus, the SVC of periodic cracks can be tailored to obtain TBCs with high strain tolerance.
Design and Optimization of the Antireflective Coating Properties of Silicon Solar Cells by Using Response Surface Methodology
Authors: Makableh Yahia F. , Alzubi Hani , Tashtoush Ghassan
Published: June 2021

The design and optimization of a nanostructured antireflective coatings for Si solar cells were performed by using response surface methodology (RSM). RSM was employed to investigate the effect on the overall optical performance of silicon solar cells coated with three different nanoparticle materials of titanium dioxide, aluminum oxide, and zinc oxide nanostructures. Central composite design was used for the optimization of the reflectance process and to study the main effects and interactions between the three process variables: nanomaterial type, the radius of nanoparticles, and wavelength of visible light. In this theoretical study, COMSOL Multiphysics was utilized to design the structures by using the wave optics module. The optical properties of the solar cell’s substrate and the three different nanomaterial types were studied. The results indicated that ZnO nanoparticles were the best antireflective coating candidate for Si, as the ZnO nanoparticles produced the lowest reflection values among the three nanomaterial types. The study reveals that the optimum conditions to reach minimum surface reflections for silicon solar cell were established by using ZnO nanoparticles with a radius of ~38 nm. On average, the reflectance reached ~5.5% along the visible spectral range, and approximately zero reflectance in the 550–600 nm range.
Water and Ion Dynamics in Confined Media: A Multi-Scale Study of the Clay/Water Interface
Authors: Porion Patrice , Asaad Ali , Dabat Thomas , Dazas Baptiste , Delville Alfred , Ferrage Eric , Hubert Fabien , Jiménez-Ruiz Mónica , Michot Laurent J. , Savoye Sébastien , Tertre Emmanuel
Published: June 2021

This review details a large panel of experimental studies (Inelastic Neutron Scattering, Quasi-Elastic Neutron Scattering, Nuclear Magnetic Resonance relaxometry, Pulsed-Gradient Spin-Echo attenuation, Nuclear Magnetic Resonance Imaging, macroscopic diffusion experiments) used recently to probe, over a large distribution of characteristic times (from pico-second up to days), the dynamical properties of water molecules and neutralizing cations diffusing within clay/water interfacial media. The purpose of this review is not to describe these various experimental methods in detail but, rather, to investigate the specific dynamical information obtained by each of them concerning these clay/water interfacial media. In addition, this review also illustrates the various numerical methods (quantum Density Functional Theory, classical Molecular Dynamics, Brownian Dynamics, macroscopic differential equations) used to interpret these various experimental data by analyzing the corresponding multi-scale dynamical processes. The purpose of this multi-scale study is to perform a bottom-up analysis of the dynamical properties of confined ions and water molecules, by using complementary experimental and numerical studies covering a broad range of diffusion times (between pico-seconds up to days) and corresponding diffusion lengths (between Angstroms and centimeters). In the context of such a bottom-up approach, the numerical modeling of the dynamical properties of the diffusing probes is based on experimental or numerical investigations performed on a smaller scale, thus avoiding the use of empirical or fitted parameters.
Synthesis, Structural Studies, and Anticancer Properties of [CuBr(PPh3)2(4,6-Dimethyl-2-Thiopyrimidine-κS]
Authors: Babgi Bandar A. , Alsayari Jalal H. , Davaasuren Bambar , Emwas Abdul-Hamid , Jaremko Mariusz , Abdellattif Magda H. , Hussien Mostafa A.
Published: June 2021

CuBr(PPh3)2(4,6-dimethylpyrimidine-2-thione) (Cu-L) was synthesized by stirring CuBr(PPh3)3 and 4,6-dimethylpyrimidine-2-thione in dichloromethane. The crystal structure of Cu-L was obtained, and indicated that the complex adopts a distorted tetrahedral structure with several intramolecular hydrogen bonds. Moreover, a centrosymmetric dimer is formed by the intermolecular hydrogen bonding of the bromine acceptor created by symmetry operation 1−x, 1−y, 1−z to the methyl group (D3 = C42) of the pyrimidine–thione ligand. HSA-binding of Cu-L and its ligand were evaluated, revealing that Cu-L binds to HSA differently than its ligand. The HSA-bindings were modeled by molecular docking, which suggested that Cu-L binds to the II A domain while L binds between the I B and II A domains. Anticancer activities toward OVCAR-3 and HeLa cell lines were tested and indicated the significance of the copper center in enhancing the cytotoxic effect; negligible toxicities for L and Cu-L were observed towards a non-cancer cell line. The current study highlights the potential of copper(I)-phosphine complexes containing thione ligands as therapeutic agents.
Forecasting the Walking Assistance Rehabilitation Level of Stroke Patients Using Artificial Intelligence
Authors: Seo Kanghyeon , Chung Bokjin , Panchaseelan Hamsa Priya , Kim Taewoo , Park Hyejung , Oh Byungmo , Chun Minho , Won Sunjae , Kim Donkyu , Beom Jaewon , Jeon Doyoung , Yang Jihoon
Published: June 2021

Cerebrovascular accidents (CVA) cause a range of impairments in coordination, such as a spectrum of walking impairments ranging from mild gait imbalance to complete loss of mobility. Patients with CVA need personalized approaches tailored to their degree of walking impairment for effective rehabilitation. This paper aims to evaluate the validity of using various machine learning (ML) and deep learning (DL) classification models (support vector machine, Decision Tree, Perceptron, Light Gradient Boosting Machine, AutoGluon, SuperTML, and TabNet) for automated classification of walking assistant devices for CVA patients. We reviewed a total of 383 CVA patients’ (1623 observations) prescription data for eight different walking assistant devices from five hospitals. Among the classification models, the advanced tree-based classification models (LightGBM and tree models in AutoGluon) achieved classification results of over 90% accuracy, recall, precision, and F1-score. In particular, AutoGluon not only presented the highest predictive performance (almost 92% in accuracy, recall, precision, and F1-score, and 86.8% in balanced accuracy) but also demonstrated that the classification performances of the tree-based models were higher than that of the other models on its leaderboard. Therefore, we believe that tree-based classification models have potential as practical diagnosis tools for medical rehabilitation.
Prediction Models of Obstructive Sleep Apnea in Pregnancy: A Systematic Review and Meta-Analysis of Model Performance
Authors: Siriyotha Sukanya , Tantrakul Visasiri , Plitphonganphim Supada , Rattanasiri Sasivimol , Thakkinstian Ammarin
Published: June 2021

Background: Gestational obstructive sleep apnea (OSA) is associated with adverse maternal and fetal outcomes. Timely diagnosis and treatment are crucial to improve pregnancy outcomes. Conventional OSA screening questionnaires are less accurate, and various prediction models have been studied specifically during pregnancy. Methods: A systematic review and meta-analysis were performed for multivariable prediction models of both development and validation involving diagnosis of OSA during pregnancy. Results: Of 1262 articles, only 6 studies (3713 participants) met the inclusion criteria and were included for review. All studies showed high risk of bias for the construct of models. The pooled C-statistics (95%CI) for development prediction models was 0.817 (0.783, 0850), I2 = 97.81 and 0.855 (0.822, 0.887), I2 = 98.06 for the first and second–third trimesters, respectively. Only multivariable apnea prediction (MVAP), and Facco models were externally validated with pooled C-statistics (95%CI) of 0.743 (0.688, 0.798), I2 = 95.84, and 0.791 (0.767, 0.815), I2 = 77.34, respectively. The most common predictors in the models were body mass index, age, and snoring, none included hypersomnolence. Conclusions: Prediction models for gestational OSA showed good performance during early and late trimesters. A high level of heterogeneity and few external validations were found indicating limitation for generalizability and the need for further studies.
Evaluation of Quantitative Ga-68 PSMA PET/CT Repeatability of Recurrent Prostate Cancer Lesions Using Both OSEM and Bayesian Penalized Likelihood Reconstruction Algorithms
Authors: Roef Mark J. , Rijnsdorp Sjoerd , Brouwer Christel , Wyndaele Dirk N. , Arends Albert J.
Published: June 2021

Rationale: To formally determine the repeatability of Ga-68 PSMA lesion uptake in both relapsing and metastatic tumor. In addition, it was hypothesized that the BPL algorithm Q. Clear has the ability to lower SUV signal variability in the small lesions typically encountered in Ga-68 PSMA PET imaging of prostate cancer. Methods: Patients with biochemical recurrence of prostate cancer were prospectively enrolled in this single center pilot test-retest study and underwent two Ga-68 PSMA PET/CT scans within 7.9 days on average. Lesions were classified as suspected local recurrence, lymph node metastases or bone metastases. Two datasets were generated: one standard PSF + OSEM and one with PSF + BPL reconstruction algorithm. For tumor lesions, SUVmax was determined. Repeatability was formally assessed using Bland–Altman analysis for both BPL and standard reconstruction. Results: A total number of 65 PSMA-positive tumor lesions were found in 23 patients (range 1 to 12 lesions a patient). Overall repeatability in the 65 lesions was −1.5% ± 22.7% (SD) on standard reconstructions and −2.1% ± 29.1% (SD) on BPL reconstructions. Ga-68 PSMA SUVmax had upper and lower limits of agreement of +42.9% and −45.9% for standard reconstructions and +55.0% and −59.1% for BPL reconstructions, respectively (NS). Tumor SUVmax repeatability was dependent on lesion area, with smaller lesions exhibiting poorer repeatability on both standard and BPL reconstructions (F-test, p < 0.0001). Conclusion: A minimum response of 50% seems appropriate in this clinical situation. This is more than the recommended 30% for other radiotracers and clinical situations (PERCIST response criteria). BPL does not seem to lower signal variability in these cases.
The Kids Are Alright: Outcome of a Safety Programme for Addressing Childhood Injury in Australia
Authors: Peck Blake , Terry Daniel
Published: June 2021

Globally, injuries are the leading cause of death and represent the highest burden of ongoing disease amongst children 1–16 years of age. Increasingly, prevention programmes are recognising a growing need for intervention strategies that target children. The purpose of this study was to determine the efficacy of the SeeMore Safety Programme, designed to teach children (4–6 years of age) how to make conscious decisions about their own capabilities related to safety and how to manage risk. This retrospective study examined de-identified pre- and post-programme data from a sample of 1027 4 to 6-year-old pre-school children over the four-year period who participated in the SeeMore Safety Programme. Results show a significant improvement in each of the post-test scores and when compared to the pre-test scores (p < 0.001). Children from rural areas, as well as those from areas of greater disadvantage, also showed significant improvement in their pre- and post-test scores (p < 0.001). Overall, the findings highlight that the SeeMore Safety Programme over the four-year period demonstrates an increase in the children’s capacity to recognise and identify danger and safety amongst all children, offering great promise for reducing the burden of injury on children, their families and society.
Flexibility Control in Autonomous Demand Response by Optimal Power Tracking
Authors: Rheinberger Klaus , Kepplinger Peter , Preißinger Markus
Published: June 2021

In the regime of incentive-based autonomous demand response, time dependent prices are typically used to serve as signals from a system operator to consumers. However, this approach has been shown to be problematic from various perspectives. We clarify these shortcomings in a geometric way and thereby motivate the use of power signals instead of price signals. The main contribution of this paper consists of demonstrating in a standard setting that power tracking signals can control flexibilities more efficiently than real-time price signals. For comparison by simulation, German renewable energy production and German standard load profiles are used for daily production and demand profiles, respectively. As for flexibility, an energy storage system with realistic efficiencies is considered. Most critically, the new approach is able to induce consumptions on the demand side that real-time pricing is unable to induce. Moreover, the pricing approach is outperformed with regards to imbalance energy, peak consumption, storage variation, and storage losses without the need for additional communication or computation efforts. It is further shown that the advantages of the optimal power tracking approach compared to the pricing approach increase with the extent of the flexibility. The results indicate that autonomous flexibility control by optimal power tracking is able to integrate renewable energy production efficiently, has additional benefits, and the potential for enhancements. The latter include data uncertainties, systems of flexibilities, and economic implementation.
A Forecast-Based Load Management Approach for Commercial Buildings Demonstrated on an Integration of BEV
Authors: Steens Thomas , Telle Jan-Simon , Hanke Benedikt , von Maydell Karsten , Agert Carsten , Di Modica Gian-Luca , Engel Bernd , Grottke Matthias
Published: June 2021

Load-forecasting problems have already been widely addressed with different approaches, granularities and objectives. Recent studies focused not only on deep learning methods but also on forecasting loads on single building level. This study aims to research problems and possibilities arising by using different load-forecasting techniques to manage loads. For that behavior of two neural networks, Long Short-Term Memory and Feed-Forward Neural Network as well as two statistical methods, standardized load profiles and personalized standardized load profiles are analyzed and assessed by using a sliding-window forecast approach. The results show that personalized standardized load profiles (MAE: 3.99) can perform similar to deep learning methods (for example, LSTM MAE: 4.47). However, because of the simplistic approach, load profiles are not able to adapt to new patterns. As a case study for evaluating the support of load-forecasting for applications in energy management systems, the integration of charging stations into an existing building is simulated by using load-forecasts to schedule the charging procedures. It is shown that forecast- based controlled charging can have a significant impact by lowering overload peaks exceeding the house connection point power limit (controlled charging 20.24 kW; uncontrolled charging: 65.15 kW) while slightly increasing average charging duration. It is concluded that integration of high flexible loads can be supported by using forecast-based energy management systems with regards to their limitations.
Design and Implementation a Single-Switch Step-Up DC-DC Converter Based on Cascaded Boost and Luo Converters
Authors: Gholizadeh Hossein , Sharifi Shahrivar Reza , Hashemi Mir , Afjei Ebrahim , A. Gorji Saman
Published: June 2021

We designed and implemented a single-switch step-up DC-DC converter based on cascaded boost and Luo converters. The proposed converter demonstrated a quadratic voltage gain and a high efficiency, which makes it suitable for renewable energy applications, where a high voltage gain ratio is desired without imposing a high number of bulky items or employing a high duty cycle of the active switches. This converter benefits from the continuity of the input current waveform, which equips the maximum utilisation of renewable energy sources. While a transformer-less high voltage-gain was achieved, the voltage and current stresses of the power switch and diodes were kept low in comparison with the existing quadratic DC-DC converters. We analysed the converter in both continuous and discontinuous conduction modes. A non-ideal model of components was considered for power loss and efficiency calculations and comparisons. Finally, the simulation results were extracted with PLECS and validated with experiments on a 120 W prototype.
Opportunities and Challenges for Intensive Silviculture in Alberta, Canada
Authors: Pinno Bradley D. , Hossain Kazi L. , Gooding Ted , Lieffers Victor J.
Published: June 2021

Intensive silviculture is practiced in many parts of the world but is rare in the public forests of western Canada. Here, we make the argument that intensive silviculture could be justified in Alberta but has not been implemented due to philosophies and policy decisions by foresters from government, industry and academia. These include adherence to long rotations, management goals that are aimed at sustained total volume yield rather than economic value, limitations in the types of stands that are allowed to be regenerated and models that do not include intensive silviculture options. In Mixedwood Growth Model projections, we demonstrate the potential of intensive silviculture that includes combinations of selecting good sites and thinning to produce merchantable stands by age 50 compared to the standard rotation age of 80 with basic silviculture. There could be even more gains if forest level constraints in timber flow were removed due to the increased growth of regenerating stands. Finally, we examine the attitude and policy changes that we believe are necessary for adoption of more intensive silviculture systems on parts of Alberta’s forest landbase.
Functional Trait Responses to Strip Clearcutting in a Moso Bamboo Forest
Authors: Zheng Yaxiong , Guan Fengying , Fan Shaohui , Zhou Yang , Jing Xiong
Published: June 2021

Functional characteristics reflect plant strategies and adaptability to the changing environment. Determining the dynamics of these characteristics after harvesting would improve the understanding of forest response strategies. Strip clearcutting (SC) of moso bamboo forests, which significantly reduces the cutting cost, has been proposed to replace manual selective harvesting. A comparison of restoration features shows that 8 m is the optimal cutting width. However, the precise response of functional features to the resulting harvest-created gap remains unclear. In this study, three SC plots were selected which was performed in February 2019, with three unharvested plots as a control (C). The study focused on 10 functional traits, including leaf area (LA), specific leaf area (SLA), leaf dry matter content (LDMC), leaf nitrogen content (LNC), leaf phosphorus content (LPC), nitrogen/phosphorus ratio (N:P), wood density (WD), fine root biomass (FRB), specific fine root length (SRL), and root length density (RLD). A one-way ANOVA was used to compare differences in functional traits and soil nutrients between treatments. Strip clearcutting significantly reduced the soil organic carbon (SOC) and total nitrogen (TN) contents (p < 0.05). In terms of functional characteristics, SC significantly decreased LA and increased LNC, LPC, and N:P (p < 0.05). However, SC had no significant effect on fine root traits (p > 0.05). This study highlighted that root trait, soil content of total phosphorus (TP) and total potassium (TK) returned to the level of uncut plots after a year’s recovery. The LPC, LNC, and N:P were negatively correlated with LA, and LDMC and WD were negatively correlated with SLA, while the effect of SC on fine root traits was limited (p > 0.05). Fine root traits (FRB, RLD, and SRL) were positively associated with SOC, TN, and TP, but negatively correlated with TK. The changes in soil nutrient content caused by the removal of biomass were normal. Increased light and the rapid growth of new trees will increase nutrient regressions; therefore, these results further confirm the feasibility of SC.
Differing Responses to Cryphonectria parasitica at Two Indiana Locations
Authors: Lawson Shaneka S. , Ebrahimi Aziz , McKenna James R.
Published: June 2021

Chestnut blight, a disease that has spread rampantly among American (Castanea dentata (Marsh.) Borkh.) and European chestnut (C. sativa Mill.) trees, results from infection by the fungal pathogen Cryphonectria parasitica (Murrill) M.E. Barr (C. parasitica). This fungus was introduced in the early 1900s and has almost functionally eliminated chestnut trees from the North American landscape. In 2017, we collected chestnut blight samples from two sites (Site B, (Fulton Co., IN) and Site C (Marshall Co., IN)). At the Fulton County planting, Site B, cankers had formed, healed over, and the trees were healthy. However, at the second site in Marshall County, (Site C), cankers continued to propagate until all of the chestnut trees had died back to the ground. Research evidence worldwide has indicated that these visual clues likely result from the presence of a hypovirus. Upon closer inspection and the subsequent isolation and reproduction of spores, no hypovirus has been identified from either site. Here, we present a curious coincidence where one site has completely succumbed to the disease, while the other has been able to spring back to health.
Two-Phase Flow Mass Transfer Analysis of Airlift Pump for Aquaculture Applications
Authors: Abed Rashal , Hussein Mohamed M. , Ahmed Wael H. , Abdou Sherif
Published: June 2021

Airlift pumps can be used in the aquaculture industry to provide aeration while concurrently moving water utilizing the dynamics of two-phase flow in the pump riser. The oxygen mass transfer that occurs from the injected compressed air to the water in the aquaculture systems can be experimentally investigated to determine the pump aeration capabilities. The objective of this study is to evaluate the effects of various airflow rates as well as the injection methods on the oxygen transfer rate within a dual injector airlift pump system. Experiments were conducted using an airlift pump connected to a vertical pump riser within a recirculating system. Both two-phase flow patterns and the void fraction measurements were used to evaluate the dissolved oxygen mass transfer mechanism through the airlift pump. A dissolved oxygen (DO) sensor was used to determine the DO levels within the airlift pumping system at different operating conditions required by the pump. Flow visualization imaging and particle image velocimetry (PIV) measurements were performed in order to better understand the effects of the two-phase flow patterns on the aeration performance. It was found that the radial injection method reached the saturation point faster at lower airflow rates, whereas the axial method performed better as the airflow rates were increased. The standard oxygen transfer rate (SOTR) and standard aeration efficiency (SAE) were calculated and were found to strongly depend on the injection method as well as the two-phase flow patterns in the pump riser.
Palatability and Swallowability of Pimavanserin When Mixed with Selected Food Vehicles: An Exploratory Open-Label Crossover Study
Authors: Forman Mark , Kouassi Alex , Brandt Teresa , Barsky Lee , Zamora Cynthia , Dekarske Daryl
Published: June 2021

Dysphagia (difficulty swallowing) affects up to 13% of persons 65 years and older and 51% of older persons in nursing homes and can contribute to reduced adherence to oral medications. This was an exploratory, single-center, open-label, randomized, crossover study in healthy older adult participants. Primary objectives were evaluation of palatability (taste) and swallowability of the contents of pimavanserin 34 mg capsules mixed with selected soft foods or a liquid nutritional supplement. Secondary objectives included evaluation of additional palatability endpoints and ease of capsule manipulation for mixing. A total of 18 healthy, older adult participants (mean age 65 years) were included. Mean participant ratings for all food vehicles were “moderately like” to “neither like nor dislike” for palatability and “very easy” to “somewhat easy” for swallowability. Capsule manipulation to allow sprinkling of contents was rated “very easy” or “somewhat easy” by most participants. There were five treatment-emergent adverse events, all mild; two were deemed related to study treatment. The palatability and swallowability of pimavanserin was considered acceptable when administered with certain soft foods or a liquid nutritional supplement by the study participants.
Methods to Address Self-Selection and Reverse Causation in Studies of Neighborhood Environments and Brain Health
Authors: Besser Lilah M. , Brenowitz Willa D. , Meyer Oanh L. , Hoermann Serena , Renne John
Published: June 2021

Preliminary evidence suggests that neighborhood environments, such as socioeconomic disadvantage, pedestrian and physical activity infrastructure, and availability of neighborhood destinations (e.g., parks), may be associated with late-life cognitive functioning and risk of Alzheimer’s disease and related disorders (ADRD). The supposition is that these neighborhood characteristics are associated with factors such as mental health, environmental exposures, health behaviors, and social determinants of health that in turn promote or diminish cognitive reserve and resilience in later life. However, observed associations may be biased by self-selection or reverse causation, such as when individuals with better cognition move to denser neighborhoods because they prefer many destinations within walking distance of home, or when individuals with deteriorating health choose residences offering health services in neighborhoods in rural or suburban areas (e.g., assisted living). Research on neighborhood environments and ADRD has typically focused on late-life brain health outcomes, which makes it difficult to disentangle true associations from associations that result from reverse causality. In this paper, we review study designs and methods to help reduce bias due to reverse causality and self-selection, while drawing attention to the unique aspects of these approaches when conducting research on neighborhoods and brain aging.
From Isolation to Containment: Perceived Fear of Infectivity and Protective Behavioral Changes during the COVID-19 Vaccination Campaign
Authors: Kaim Arielle , Siman-Tov Maya , Jaffe Eli , Adini Bruria
Published: June 2021

In the ongoing COVID-19 pandemic, maintenance of protective behavior is a continued challenge in the effort to contain the spread of the virus. A cross-sectional study via an internet questionnaire was utilized to elucidate changes in compliance to protective behavior among the Israeli population (n = 1120), after the beginning of the vaccination campaign. Comparison was made between individuals who were previously infected with the virus, those who received one dose of inoculation with the vaccine, and individuals that were neither infected or vaccinated. The study results indicate that those who were previously infected with the COVID-19 virus were less careful about mask wearing (18.8%) and social distancing (29.7%), as compared to the other examined groups (regarding mask wearing, 8.2% and 11.6% respectively, and with regard to social distancing 12.8% and 19.2%), and may require targeted risk communication campaigns to address this population. Furthermore, the study revealed that those that were non-Jewish (as compared to Jewish study counterparts) or that were older (19+) were more vigilant in their protective behavior (29.6% vs. 11.2% respectively for social distancing and 29.6% vs. 11.1% respectively for mask wearing). Despite a successful initial vaccination campaign in Israel, public health officials need to engage all members of the public to unremittingly observe compliance to directed health guidelines, to ensure that the results of previous governmental efforts in fighting the pandemic (such as lockdowns) will be effectively sustained, and the road to containment will be hastened.
The Diverse Roles of TNNI3K in Cardiac Disease and Potential for Treatment
Authors: Pham Caroline , Muñoz-Martín Noelia , Lodder Elisabeth M.
Published: June 2021

In the two decades since the discovery of TNNI3K it has been implicated in multiple cardiac phenotypes and physiological processes. TNNI3K is an understudied kinase, which is mainly expressed in the heart. Human genetic variants in TNNI3K are associated with supraventricular arrhythmias, conduction disease, and cardiomyopathy. Furthermore, studies in mice implicate the gene in cardiac hypertrophy, cardiac regeneration, and recovery after ischemia/reperfusion injury. Several new papers on TNNI3K have been published since the last overview, broadening the clinical perspective of TNNI3K variants and our understanding of the underlying molecular biology. We here provide an overview of the role of TNNI3K in cardiomyopathy and arrhythmia covering both a clinical perspective and basic science advancements. In addition, we review the potential of TNNI3K as a target for clinical treatments in different cardiac diseases.
Radiodynamic Therapy Using TAT Peptide-Targeted Verteporfin-Encapsulated PLGA Nanoparticles
Authors: Clement Sandhya , Anwer Ayad , Pires Layla , Campbell Jared , Wilson Brian , Goldys Ewa
Published: June 2021

Radiodynamic therapy (RDT) is a recent extension of conventional photodynamic therapy, in which visible/near infrared light irradiation is replaced by a well-tolerated dose of high-energy X-rays. This enables greater tissue penetration to allow non-invasive treatment of large, deep-seated tumors. We report here the design and testing of a drug delivery system for RDT that is intended to enhance intra- or peri-nuclear localization of the photosensitizer, leading to DNA damage and resulting clonogenic cell kill. This comprises a photosensitizer (Verteporfin, VP) incorporated into poly (lactic-co-glycolic acid) nanoparticles (PLGA NPs) that are surface-functionalized with a cell-penetrating HIV trans-activator of transcription (TAT) peptide. In addition to a series of physical and photophysical characterization studies, cytotoxicity tests in pancreatic (PANC-1) cancer cells in vitro under 4 Gy X-ray exposure from a clinical 6 MV linear accelerator (LINAC) showed that TAT targeting of the nanoparticles markedly enhances the effectiveness of RDT treatment, particularly when assessed by a clonogenic, i.e., DNA damage-mediated, cell kill.
Insulin-Like Growth Factor 1 (IGF-1) Signaling in Glucose Metabolism in Colorectal Cancer
Authors: Kasprzak Aldona
Published: June 2021

Colorectal cancer (CRC) is one of the most common aggressive carcinoma types worldwide, characterized by unfavorable curative effect and poor prognosis. Epidemiological data re-vealed that CRC risk is increased in patients with metabolic syndrome (MetS) and its serum components (e.g., hyperglycemia). High glycemic index diets, which chronically raise post-prandial blood glucose, may at least in part increase colon cancer risk via the insulin/insulin-like growth factor 1 (IGF-1) signaling pathway. However, the underlying mechanisms linking IGF-1 and MetS are still poorly understood. Hyperactivated glucose uptake and aerobic glycolysis (the Warburg effect) are considered as a one of six hallmarks of cancer, including CRC. However, the role of insulin/IGF-1 signaling during the acquisition of the Warburg metabolic phenotypes by CRC cells is still poorly understood. It most likely results from the interaction of multiple processes, directly or indirectly regulated by IGF-1, such as activation of PI3K/Akt/mTORC, and Raf/MAPK signaling pathways, activation of glucose transporters (e.g., GLUT1), activation of key glycolytic enzymes (e.g., LDHA, LDH5, HK II, and PFKFB3), aberrant expression of the oncogenes (e.g., MYC, and KRAS) and/or overexpression of signaling proteins (e.g., HIF-1, TGF-β1, PI3K, ERK, Akt, and mTOR). This review describes the role of IGF-1 in glucose metabolism in physiology and colorectal carcinogenesis, including the role of the insulin/IGF system in the Warburg effect. Furthermore, current therapeutic strategies aimed at repairing impaired glucose metabolism in CRC are indicated.
Excited States of Bromopyrimidines Probed by VUV Photoabsorption Spectroscopy and Theoretical Calculations
Authors: Mendes Mónica , Kossoski Fábris , Lozano Ana I. , Pereira-da-Silva João , Rodrigues Rodrigo , Ameixa João , Jones Nykola C. , Hoffmann Søren V. , Ferreira da Silva Filipe
Published: June 2021

We report absolute photoabsorption cross sections for gas-phase 2- and 5-bromopyrimidine in the 3.7–10.8 eV energy range, in a joint theoretical and experimental study. The measurements were carried out using high-resolution vacuum ultraviolet synchrotron radiation, with quantum chemical calculations performed through the nuclear ensemble approach in combination with time-dependent density functional theory, along with additional Franck–Condon Herzberg–Teller calculations for the first absorption band (3.7–4.6 eV). The cross sections of both bromopyrimidines are very similar below 7.3 eV, deviating more substantially from each other at higher energies. In the 7.3–9.0 eV range where the maximum cross-section is found, a single and broad band is observed for 5-bromopyrimidine, while more discernible features appear in the case of 2-bromopyrimidine. Several π* ← π transitions account for the most intense bands, while weaker ones are assigned to transitions involving the nitrogen and bromine lone pairs, the antibonding σ*Br orbital, and the lower-lying Rydberg states. A detailed comparison with the available photo-absorption data of bromobenzene is also reported. We have found significant differences regarding the main absorption band, which is more peaked in bromobenzene, becoming broader and shifting to higher energies in both bromopyrimidines. In addition, there is a significant suppression of vibrational structures and of Rydberg states in the pair of isomers, most noticeably for 2-bromopyrimidine.
Volatility Spillovers among Developed and Developing Countries: The Global Foreign Exchange Markets
Authors: Mohammed Walid Abass
Published: June 2021

In this paper, we investigate the “static and dynamic” return and volatility spillovers’ transmission across developed and developing countries. Quoted against the US dollar, we study twenty-three global currencies over the time period 2005–2016. Focusing on the spillover index methodology, the generalised VAR framework is employed. Our findings indicate no evidence of bi-directional return and volatility spillovers between developed and developing countries. However, unidirectional volatility spillovers from developed to developing countries are highlighted. Furthermore, our findings document significant bi-directional volatility spillovers within the European region (Eurozone and non-Eurozone currencies) with the British pound sterling (GBP) and the Euro (EUR) as the most significant transmitters of volatility. The findings reiterate the prominence of volatility spillovers to financial regulators.