bluuebunny/crossref_metadata_2025 huggingface dataset:
Reliability Analysis of the Main Pier during the Construction Period of HLCR Bridges
Authors: Qi Ningning , Xu Baosheng , Zhang Tianjing , Li Qingfu
Published: June 2022

In the process of cradle construction for high-pier, long-span, continuous, rigid-frame (HLCR) bridges, the strength failure and instability damage of the main pier will directly affect the bridge construction safety. Therefore, it is necessary to study the reliability of the main pier during the construction of HLCR bridges. This paper starts from the factors that easily affect the stability of the main pier during HLCR bridge cradle construction, establishes the resistance and load probability model of the main pier during the maximum cantilever stage and the maximum unbalanced load of the continuous, rigid-frame bridge’s hanging cradles, fully considers the influence of random factors on the reliability of the pier, and calculates and analyzes the reliability index β through calculation examples. The results show that the changes of various random factors during the construction process have different degrees of influence on the reliability of the bridge pier. Our work provides a basis for the safe control of hanging cradles in the construction of HLCR bridges.
Performance Evaluation of Enterprise Collaboration Based on an Improved Elman Neural Network and AHP-EW
Authors: Zhang Jianxiong , Ding Xuefeng , Hu Dasha , Guo Bing , Jiang Yuming
Published: June 2022

In order to mitigate the influence of human subjectivity on indicator weights in the performance evaluation of enterprise collaboration, and explore the nonlinear relationship between the enterprise collaboration influencing factors and the evaluation results, this paper propose a combined performance evaluation model based on AHP-EW and an improved Elman neural network. Firstly, based on the characteristics of collaboration among manufacturing enterprises, the evaluation system for the collaborative performance of manufacturing enterprises is constructed from three dimensions. Moreover, this study combines subjective and objective weighting methods to obtain comprehensive weights that take into account both expert experience and objective information. Then, an improved Elman neural network is proposed and trained to predict and evaluate the collaborative performance indicator data, which greatly shortens the evaluation time and improves evaluation accuracy. The experimental results show that the proposed model has a faster convergence speed and higher accuracy, which will provide a valuable reference for decision making and the management of enterprise collaboration.
Improving Sustainability of Steel Roofs: Life Cycle Assessment of a Case Study Roof
Authors: Roy Krishanu , Dani Aflah Alamsah , Ichhpuni Hartej , Fang Zhiyuan , Lim James B. P.
Published: June 2022

In New Zealand (NZ), steel roofing is the most common roofing type for residential buildings. However, the environmental impact of steel roofs are not negligible. Steel roofs account for up to 30% of the upfront embodied carbon for a typical NZ house, highlighting the importance of investigating and reducing the environmental impacts of steel roofs in meeting the net-zero carbon goal of the NZ government. There are several research gaps in investigating the impacts of steel roofs, such as the variation in emissions between local and imported steel coil products, the unavailability of life cycle assessment (LCA) data, and additional impacts from ancillary items. Therefore, this study performed an LCA of a case study roof in NZ to investigate these gaps using GaBi Ts software. It was found that the overall impacts from the steel roofs, including the ancillary items, were 12 kg CO2-eq/m2, where the ancillary items accounted for less than 10% of total emissions. The prepainted steel coils manufactured globally had less than 70% emissions when compared to the emissions of locally manufactured prepainted steel coils. In addition, the roll forming processes had an insignificant effect on overall emissions, whereas the transportation of steel coils had a notable impact.
Application of Deep Learning and Neural Network to Speeding Ticket and Insurance Claim Count Data
Authors: Kim Jong-Min , Kim Jihun , Ha Il Do
Published: June 2022

With the popularity of big data analysis with insurance claim count data, diverse regression models for count response variable have been developed. However, there is a multicollinearlity issue with multivariate input variables to the count response regression models. Recently, deep learning and neural network models for count response have been proposed, and a Keras and Tensorflow-based deep learning model has been also proposed. To apply the deep learning and neural network models to non-normal insurance claim count data, we perform the root mean square error accuracy comparison of gradient boosting machines (a popular machine learning regression tree algorithm), principal component analysis (PCA)-based Poisson regression, PCA-based negative binomial regression, and PCA-based zero inflated poisson regression to avoid the multicollinearity of multivariate input variables with the simulated normal distribution data and the non-normal simulated data combined with normally distributed data, binary data, copula-based asymmetrical data, and two real data sets, which consist of speeding ticket and Singapore insurance claim count data.
Controllability of a Class of Impulsive ψ-Caputo Fractional Evolution Equations of Sobolev Type
Authors: Yang Qing , Bai Chuanzhi , Yang Dandan
Published: June 2022

In this paper, we investigate the controllability of a class of impulsive ψ-Caputo fractional evolution equations of Sobolev type in Banach spaces. Sufficient conditions are presented by two new characteristic solution operators, fractional calculus, and Schauder fixed point theorem. Our works are generalizations and continuations of the recent results about controllability of a class of impulsive ψ-Caputo fractional evolution equations. Finally, an example is given to illustrate the effectiveness of the main results.
Enhancing Night and Day Circadian Contrast through Sleep Education in Prediabetes and Type 2 Diabetes Mellitus: A Randomized Controlled Trial
Authors: García-Serrano Cristina , Pujol Salud Jesús , Aran-Solé Lidia , Sol Joaquim , Ortiz-Congost Sònia , Artigues-Barberà Eva , Ortega-Bravo Marta
Published: June 2022

Background: Evidence supports a causal relationship between circadian disturbance and impaired glucose homeostasis. Methods: To determine the effect of an educational intervention delivered by primary care nurses to improve sleep hygiene, a parallel, open-label clinical trial in subjects aged 18 and older with impaired fasting glucose (IFG) or type 2 diabetes mellitus (T2DM) was performed. Study variables were sex, age, fasting glucose, glycated haemoglobin A1c (HbA1c), Pittsburgh Sleep Quality Index (PSQI), sleep duration and efficiency, body mass index, antidiabetic treatment, diet and physical exercise. An individual informative educational intervention was carried out following a bidirectional feedback method. The intervention aimed to develop skills to improve sleep through nine simple tips. An analysis of covariance was performed on all the mean centred outcome variables controlling for the respective baseline scores. Results: In the intervention group, PSQI dropped, the duration and quality of sleep increased, and a decrease in fasting glucose and in HbA1c levels was observed. Conclusion: The proposed intervention is effective for improving sleep quality, length and efficiency, and for decreasing fasting glucose and HbA1c levels in only 3 months. These findings support the importance of sleep and circadian rhythm education focused on improving IFG and T2DM.
Molecular Pathogenesis and New Therapeutic Dimensions for Spinal Muscular Atrophy
Authors: López-Cortés Andrés , Echeverría-Garcés Gabriela , Ramos-Medina María José
Published: June 2022

The condition known as 5q spinal muscular atrophy (SMA) is a devastating autosomal recessive neuromuscular disease caused by a deficiency of the ubiquitous protein survival of motor neuron (SMN), which is encoded by the SMN1 and SMN2 genes. It is one of the most common pediatric recessive genetic diseases, and it represents the most common cause of hereditary infant mortality. After decades of intensive basic and clinical research efforts, and improvements in the standard of care, successful therapeutic milestones have been developed, delaying the progression of 5q SMA and increasing patient survival. At the same time, promising data from early-stage clinical trials have indicated that additional therapeutic options are likely to emerge in the near future. Here, we provide updated information on the molecular underpinnings of SMA; we also provide an overview of the rapidly evolving therapeutic landscape for SMA, including SMN-targeted therapies, SMN-independent therapies, and combinational therapies that are likely to be key for the development of treatments that are effective across a patient’s lifespan.
Desert Ants Learn to Avoid Pitfall Traps While Foraging
Authors: Bar Adi , Marom Chen , Zorin Nikol , Gilad Tomer , Subach Aziz , Foitzik Susanne , Scharf Inon
Published: June 2022

Central-place foragers, such as social insects or nesting birds, repeatedly use the same routes from and to their nests when foraging for food. Such species forage more efficiently after accumulating experience. We examined, here, a relatively neglected aspect of such an improvement with experience—the avoidance of pitfall traps. Similar pits are built by antlions, which co-occur with the ants, but they also resemble other natural obstacles. We used the desert ant Cataglyphis niger, common in sandy habitats, and allowed it to forage for three successive runs for a food reward. Ant workers discovered food more slowly and in smaller numbers when pits were in their path. Pit presence also led to longer tracks by ants and slower movement. However, with experience, the ants fell into such pits less often and reached the food more quickly. To understand how past conditions affect current behavior, we investigated whether removing or adding pits led to a different result to that with a constant number of pits. Workers adjusted their behavior immediately when conditions changed. The only carryover effect was the longer tracks crossed by workers after pit removal, possibly resulting from the mismatch between the past and current conditions. Finally, the workers were more likely to fall into pits that were closer to the nest than those that were further away. This is a good example of the advantage that ambush predators can derive from ambushing their prey in specific locations.
Inhibitors of the Cancer Target Ribonucleotide Reductase, Past and Present
Authors: Huff Sarah E. , Winter Jordan M. , Dealwis Chris G.
Published: June 2022

Ribonucleotide reductase (RR) is an essential multi-subunit enzyme found in all living organisms; it catalyzes the rate-limiting step in dNTP synthesis, namely, the conversion of ribonucleoside diphosphates to deoxyribonucleoside diphosphates. As expression levels of human RR (hRR) are high during cell replication, hRR has long been considered an attractive drug target for a range of proliferative diseases, including cancer. While there are many excellent reviews regarding the structure, function, and clinical importance of hRR, recent years have seen an increase in novel approaches to inhibiting hRR that merit an updated discussion of the existing inhibitors and strategies to target this enzyme. In this review, we discuss the mechanisms and clinical applications of classic nucleoside analog inhibitors of hRRM1 (large catalytic subunit), including gemcitabine and clofarabine, as well as inhibitors of the hRRM2 (free radical housing small subunit), including triapine and hydroxyurea. Additionally, we discuss novel approaches to targeting RR and the discovery of new classes of hRR inhibitors.
AKT, a Key Transmitter of HIF-1α and AR Signaling Pathways, Has a Critical Role in the Apigetrin-Mediated Anti-Cancer Effects in Prostate Cancer Cells
Authors: Lee You-Kyung , Kim Jung-Eun , Xu Yinzhu , Han Hengmin , Lee Jae-Hyeon , Lee Hyo-Jeong
Published: June 2022

Apigetrin is a flavonoid glycoside phytochemical that is derived from various herbs and exhibits several beneficial biological activities, including anti-oxidant, anti-inflammatory, anti-obesity, and anti-cancer effects. In the present study, we elucidated the anti-cancer effect and targeting mechanism of apigetrin in LNCaP and PC-3 cells through various experiments, including cell viability by CELLOMAXTM Viability Assay kit, cell migration by scratch wound assays, and 2D-and 3D- cell growth assay. Apigetrin inhibited the viability, migration, proliferation, and growth of cells in long-term 2D- and 3D- cultures cell growth. A high dose of apigetrin induced apoptosis, as evidenced by increased cleavage of poly ADP-ribose polymerase (PARP) and caspase-3 (c-cas3) in both LNCaP and PC-3 cells. Furthermore, apigetrin inhibited AR, PSA, HIF-1α, and VEGF expression in LNCaP and PC-3 cells. Apigetrin also suppressed the hypoxia-induced HIF-1α expression in these cells. Furthermore, apigetrin reduced hypoxia-induced VEGF secretion in the culture medium and inhibited hypoxia-induced tube formation of HUVECs. Silencing of AKT revealed that the anti-cancer activity of apigetrin is mediated via AKT. Thus, our data suggest that apigetrin exerts anti-cancer effects by inhibiting AKT, a central key of HIF-1α and AR signaling, in early-and late-stage prostate cancer cells.
State of the Art in Carbon Nanomaterials for Photoacoustic Imaging
Authors: Kang Moon Sung , Lee Haeni , Jeong Seung Jo , Eom Tae Joong , Kim Jeesu , Han Dong-Wook
Published: June 2022

Photoacoustic imaging using energy conversion from light to ultrasound waves has been developed as a powerful tool to investigate in vivo phenomena due to their complex characteristics. In photoacoustic imaging, endogenous chromophores such as oxygenated hemoglobin, deoxygenated hemoglobin, melanin, and lipid provide useful biomedical information at the molecular level. However, these intrinsic absorbers show strong absorbance only in visible or infrared optical windows and have limited light transmission, making them difficult to apply for clinical translation. Therefore, the development of novel exogenous contrast agents capable of increasing imaging depth while ensuring strong light absorption is required. We report here the application of carbon nanomaterials that exhibit unique physical, mechanical, and electrochemical properties as imaging probes in photoacoustic imaging. Classified into specific structures, carbon nanomaterials are synthesized with different substances according to the imaging purposes to modulate the absorption spectra and highly enhance photoacoustic signals. In addition, functional drugs can be loaded into the carbon nanomaterials composite, and effective in vivo monitoring and photothermal therapy can be performed with cell-specific targeting. Diverse applied cases suggest the high potential of carbon nanomaterial-based photoacoustic imaging in in vivo monitoring for clinical research.
A Narrative Review of 99mTc-Aprotinin in the Diagnosis of Cardiac Amyloidosis and a New Life for an Unfairly Abandoned Drug
Authors: Aprile Carlo , Lodola Lorenzo
Published: June 2022

Several studies investigated the use of 99mTc-labelled Aprotinin as an amyloid seeker some years ago. In vitro tests showed high binding affinity for several types of amyloid fibrils accompanied by an excellent specificity. Initial human studies demonstrated good accuracy in detecting cardiac involvement. Scintigraphy results were confirmed in a group of 28 endomyocardial biopsies. Unfortunately, clinical studies were halted because of a temporary suspension of the vector protein (Trasylol) and public health concerns over prion contamination of the bovine origin compound. To obviate these limitations, efforts have been made to label a recombinant Aprotinin with 99mTc, which exhibits the same affinity for h-insulin fibrils. With the aim of developing a PET tracer, the same recombinant protein was labeled with Gallium. The introduction of a bifunctional chelator did not affect fibril affinity. Finally, a synthetic peptidic fragment, the cyclic 30-51 SS, was synthetized. After direct technetium labeling, an impressive increase in affinity was demonstrated. This peptide appears to be a potential candidate for Gallium labeling through a bifunctional chelator for PET imaging.
Emerging Prospects of Nanozymes for Antibacterial and Anticancer Applications
Authors: Chakraborty Nayanika , Gandhi Sona , Verma Rajni , Roy Indrajit
Published: June 2022

The ability of some nanoparticles to mimic the activity of certain enzymes paves the way for several attractive biomedical applications which bolster the already impressive arsenal of nanomaterials to combat deadly diseases. A key feature of such ‘nanozymes’ is the duplication of activities of enzymes or classes of enzymes, such as catalase, superoxide dismutase, oxidase, and peroxidase which are known to modulate the oxidative balance of treated cells for facilitating a particular biological process such as cellular apoptosis. Several nanoparticles that include those of metals, metal oxides/sulfides, metal–organic frameworks, carbon-based materials, etc., have shown the ability to behave as one or more of such enzymes. As compared to natural enzymes, these artificial nanozymes are safer, less expensive, and more stable. Moreover, their catalytic activity can be tuned by changing their size, shape, surface properties, etc. In addition, they can also be engineered to demonstrate additional features, such as photoactivated hyperthermia, or be loaded with active agents for multimodal action. Several researchers have explored the nanozyme-mediated oxidative modulation for therapeutic purposes, often in combination with other diagnostic and/or therapeutic modalities, using a single probe. It has been observed that such synergistic action can effectively by-pass the various defense mechanisms adapted by rogue cells such as hypoxia, evasion of immuno-recognition, drug-rejection, etc. The emerging prospects of using several such nanoparticle platforms for the treatment of bacterial infections/diseases and cancer, along with various related challenges and opportunities, are discussed in this review.
Bioluminescence Color-Tuning Firefly Luciferases: Engineering and Prospects for Real-Time Intracellular pH Imaging and Heavy Metal Biosensing
Authors: Viviani Vadim R. , Pelentir Gabriel F. , Bevilaqua Vanessa R.
Published: June 2022

Firefly luciferases catalyze the efficient production of yellow-green light under normal physiological conditions, having been extensively used for bioanalytical purposes for over 5 decades. Under acidic conditions, high temperatures and the presence of heavy metals, they produce red light, a property that is called pH-sensitivity or pH-dependency. Despite the demand for physiological intracellular biosensors for pH and heavy metals, firefly luciferase pH and metal sensitivities were considered drawbacks in analytical assays. We first demonstrated that firefly luciferases and their pH and metal sensitivities can be harnessed to estimate intracellular pH variations and toxic metal concentrations through ratiometric analysis. Using Macrolampis sp2 firefly luciferase, the intracellular pH could be ratiometrically estimated in bacteria and then in mammalian cells. The luciferases of Macrolampis sp2 and Cratomorphus distinctus fireflies were also harnessed to ratiometrically estimate zinc, mercury and other toxic metal concentrations in the micromolar range. The temperature was also ratiometrically estimated using firefly luciferases. The identification and engineering of metal-binding sites have allowed the development of novel luciferases that are more specific to certain metals. The luciferase of the Amydetes viviani firefly was selected for its special sensitivity to cadmium and mercury, and for its stability at higher temperatures. These color-tuning luciferases can potentially be used with smartphones for hands-on field analysis of water contamination and biochemistry teaching assays. Thus, firefly luciferases are novel color-tuning sensors for intracellular pH and toxic metals. Furthermore, a single luciferase gene is potentially useful as a dual bioluminescent reporter to simultaneously report intracellular ATP and/or luciferase concentrations luminometrically, and pH or metal concentrations ratiometrically, providing a useful tool for real-time imaging of intracellular dynamics and stress.
Recent Advances in the Recognition Elements of Sensors to Detect Pyrethroids in Food: A Review
Authors: Zhang Le , Zhao Mingqi , Xiao Ming , Im Moo-Hyeog , Abd El-Aty A. M. , Shao Hua , She Yongxin
Published: June 2022

The presence of pyrethroids in food and the environment due to their excessive use and extensive application in the agriculture industry represents a significant threat to public health. Therefore, the determination of the presence of pyrethroids in foods by simple, rapid, and sensitive methods is warranted. Herein, recognition methods for pyrethroids based on electrochemical and optical biosensors from the last five years are reviewed, including surface-enhanced Raman scattering (SERS), surface plasmon resonance (SPR), chemiluminescence, biochemical, fluorescence, and colorimetric methods. In addition, recognition elements used for pyrethroid detection, including enzymes, antigens/antibodies, aptamers, and molecular-imprinted polymers, are classified and discussed based on the bioreceptor types. The current research status, the advantages and disadvantages of existing methods, and future development trends are discussed. The research progress of rapid pyrethroid detection in our laboratory is also presented.
Intra-Arterial Injection of Thrombin as Rescue Therapy of Vessel Perforation during Mechanical Thrombectomy for Acute Ischemic Stroke
Authors: Yi Tingyu , Chen Wenhuo , Wu Yanmin , Pan Zhinan , Lin Xiaohui , Lin Dinglai , Chen Rongcheng , Zheng Xiufeng
Published: June 2022

Background: Vessel perforation during stent mechanical thrombectomy (MT) is a rare and disastrous complication. A routine rescue strategy includes balloon occlusion for tamponade, procedure suspension, and lowering or normalizing blood pressure. However, this complication is still associated with poor outcome and high mortality. Objective: We present our experience with intra-arterial injection of thrombin in the treatment of vessel perforation secondary to microcatheter/microwire perforation, which prevents further deterioration in clinical outcomes. Methods: Cases with intraprocedural vessel perforation during mechanical thrombectomy were included in the final analysis. Clinical data, procedural details, and radiographic and clinical outcomes were collected. Results: Four patients with intraprocedural vessel perforation were included. Intraprocedural perforations occurred at the distal middle cerebral artery in two cases: the A2 segment in one case and the internal carotid artery terminus in one case. The etiology of four cases was intracranial atherosclerotic stenosis (ICAS). The ruptured vessels were effectively occluded in all cases. Endovascular therapy was continued in three cases, and mTICI ≥ 2b recanalization was achieved in all cases. The culprit artery was kept patent on CTA for 72 h post-operation. No active bleeding was detected on follow-up CT post-operation. During the 90-day follow-up period, one patient died, modified Rankle Scare (mRS) 3 was observed in two patients, and mRS 4 was observed in one patient. Conclusions: The key benefit of this method is occluding the ruptured vessel without affecting the following MT. We propose that intra-arterial injection of prothrombin may be simple yet effective in managing vessel perforation complications during MT.
Play Smart, Be Smart? Effect of Cognitively Engaging Physical Activity Interventions on Executive Function among Children 4~12 Years Old: A Systematic Review and Meta-Analysis
Authors: Song Wenjing , Feng Leyi , Wang Junwei , Ma Feifei , Chen Jiebo , Qu Sha , Luo Dongmei
Published: June 2022

This paper aims to collect a compendium of randomized controlled trials (RCTs) exploring the effects of cognitively engaging physical activity (PA) interventions (basketball and floorball) on various domain-specific executive functions (EFs) in children aged 4 to 12. Following the PRISMA principle, 11 articles (total sample size: 2053) were analyzed for effect size and moderating impact with Stata 13.0 software. Overall EFs (SMD = 0.21, 95% CI 0.10 to 0.32, p < 0.05), updating (SMD = 0.17, 95% CI 0.03 to 0.30, p < 0.05) and shifting (SMD = 0.32, 95% CI 0.02 to 0.61, p < 0.05) were enhanced by cognitively engaging PA interventions. Age and BMI were found to have no effect on overall EFs performance in Meta regression. Overall EFs performance was improved by interventions with a session length (≥35 min) (SMD = 0.30, 95 % CI 0.10 to 0.49, p = 0.033). The review suggests that despite the moderate effect sizes, cognitively engaging PA may be an effective approach to improving EFs in children aged 4 to 12, especially updating and shifting.
Medical Mistrust, COVID-19 Stress, and Intent to Vaccinate in Racial–Ethnic Minorities
Authors: Minaya Charlene , McKay Dean , Benton Hannah , Blanc Judite , Seixas Azizi A.
Published: June 2022

Members of the Black, Asian, and Latinx community have been particularly vulnerable to the COVID-19 pandemic but may be hesitant to vaccinate. In a December 2020 study in Black, Asian, and Latinx adults in the U.S. (n = 779), only 50% of Black respondents endorsed intending to vaccinate against COVID-19, followed by 65% and 75% of Latinx and Asian participants, respectively. Medical mistrust, fears about COVID-19 contamination, and a proclivity for compulsive checking behaviors related to COVID-19 were significant predictors of intent to vaccinate in Black respondents. Similarly, Asian respondents’ intent to vaccinate was predicted by medical mistrust, fears of the dangerous nature of the virus, and xenophobic concerns about viral spread. In Latinx participants, medical mistrust and compulsive checking for COVID-19-related information were significant predictors of intent to vaccinate. Our findings identify specific behaviors, attitudes, and beliefs we can target to inform community-wide outreach and increase the uptake of COVID-19 vaccines.
Experimental Studies on Seismic Performance of UHPSFRC-Filled Square Steel Tubular Columns
Authors: Luo Yunbiao , Zhao Yucai , Chen Yuebo , Lin Xuchuan , Yan Jiabao
Published: June 2022

The excellent seismic performance of concrete-filled steel tube (CFST) structures has been widely recognized, but there is a paucity of research on composite columns using UHPC with added steel fibers. This paper presents the experimental studies and numerical analyses with OpenSees on seismic performance of ultra-high performance steel fiber-reinforced concrete (UHPSFRC)-filled square steel tubular columns. Five half-scaled specimens of UHPSFRC-filled square steel tubular columns were tested under a combination of constant axial compression and cyclic horizontal load, with parameters of width-to-thickness ratio (28.5, 19.9 and 14.7) and axial compression ratio (0.133, 0.266 and 0.399) of the steel tube. With the decrease in width-to-thickness ratio, the maximum bending moment capacity increased by 33.5% and 15.3%, and the energy dissipation capacity and ductility increased, while the strength degradation and stiffness degradation reduced. With the increased axial compression ratio, the loading capacity increased from 55.3 to 70.2 kNm (26.94%). The results indicate that UHPSFRC-filled square steel tubular columns improve seismic performance by decreasing the axial compression ratio and by increasing the width-to-thickness ratio. When the width-to-thickness ratio was reduced, the steel tubular was able to provide higher lateral restraint to the internal UHPC; thus, seismic performance was improved. With the increase in the axial compression ratio, the second-order damage effect of the members was greatly affected, and it accelerated the plastic damage. A modified UHPSFRC model considering steel tubular constraints was adopted, and the nonlinear dynamic modeling of the column response using OpenSees led to good agreement with the tested response of the column under cyclic motion. The theoretical calculation model can better predict the bending capacity of the UHPSFRC-filled square steel tubular columns. However, the calculation formulas of initial stiffness and yield bending moment need further research.
Experimental Investigation of Seismic Performance of a Hybrid Beam–Column Connection in a Precast Concrete Frame
Authors: Chen Weihong , Xie Yujun , Guo Xiaohui , Li Dong
Published: June 2022

Prefabricated beam–column connections are the most vulnerable components of prefabricated buildings during earthquake events. The seismic performance of the beam–column connection is functional as the critical component plays a key role in structural safety. This study aimed to develop a novel hybrid prefabricated concrete (HPC) connection, combining with wet and dry connection techniques, to enhance the seismic performance of prefabricated concrete frames. A quasi-static experimental investigation was carried out to examine the seismic performance of the proposed connection. Two full-scale prefabricated connection specimens utilizing the proposed HPC connection and another code-defined monolithic prefabricated concrete (PC) connection were tested under cyclic loading, keeping the axial load on the column constant. The ductility, stiffness degradation, energy dissipation capacity, post-tensioned force, and residual displacement were obtained based on the experimental output. The results indicated that the HPC connection developed had high construction efficiency and better seismic performance than the conventional PC connection. The strength and energy dissipation capacity were significantly improved by up to 52% and 10%, respectively. The cracking and stiffness degradation were well-controlled.
Flange Contribution to the Shear Strength of RC T-Beams with Flange in Compression
Authors: Ramadan Osman M. , Abdel-Kareem Ahmed H. , El-Azab Ibrahim A. , Abousafa Hala R.
Published: June 2022

As is well known, in the current design codes, the shear strength of beams is calculated based on the modified truss theory, which does not consider the effects of the flange area of T-beams. The main objective of this paper was to gain a better understanding and enhance the experimental database of the shear behavior of RC T-beams and illustrate the contribution of the flange to the shear capacity of T-beams. To accomplish this aim, a specially designed experimental program was executed, and its test results were analyzed. The main investigated variables were flange dimensions (thickness and width) and its reinforcement (longitudinal and/or vertical). Nineteen simply supported beam specimens were tested to failure under a load configuration made of two concentrated loads. Eighteen specimens had T-shaped cross-sections, while one specimen had a rectangular cross-section for comparison purposes. The items monitored during testing included the development of diagonal cracks, concrete strains, reinforcement strains, maximum loads, and deflections. Test results showed a notable increase in the shear strength of T-beams compared to rectangular beams with the same web size. For the range of variables investigated, increasing the flange thickness-to-beam depth ratio (ρt) from 0.3 to 0.5 increased the shear capacity by up to 54%. In addition, increasing the flange width-to-web width ratio (ρb) from 3 to 5 increased the shear capacity by up to 19%. It was also shown that the results of three-dimensional finite element (FE) analyses using ANSYS compared reasonably well with the test results for all specimens. Finally, based on the test and FE results, a simplified method that accounts for the contribution of the flange to shear capacity was proposed.
Clinical Viability of Boron Neutron Capture Therapy for Personalized Radiation Treatment
Authors: Skwierawska Dominika , López-Valverde José Antonio , Balcerzyk Marcin , Leal Antonio
Published: June 2022

Boron Neutron Capture Therapy (BNCT) is a promising binary disease-targeted therapy, as neutrons preferentially kill cells labeled with boron (10B), which makes it a precision medicine treatment modality that provides a therapeutic effect exclusively on patient-specific tumor spread. Contrary to what is usual in radiotherapy, BNCT proposes cell-tailored treatment planning rather than to the tumor mass. The success of BNCT depends mainly on the sufficient spatial biodistribution of 10B located around or within neoplastic cells to produce a high-dose gradient between the tumor and healthy tissue. However, it is not yet possible to precisely determine the concentration of 10B in a specific tissue in real-time using non-invasive methods. Critical issues remain to be resolved if BNCT is to become a valuable, minimally invasive, and efficient treatment. In addition, functional imaging technologies, such as PET, can be applied to determine biological information that can be used for the combined-modality radiotherapy protocol for each specific patient. Regardless, not only imaging methods but also proteomics and gene expression methods will facilitate BNCT becoming a modality of personalized medicine. This work provides an overview of the fundamental principles, recent advances, and future directions of BNCT as cell-targeted cancer therapy for personalized radiation treatment.
Oncological Safety and Recurrence in the Surgical Treatment of Atypical Fibroxanthoma and Pleomorphic Dermal Sarcoma of the Scalp
Authors: Zeller Johannes , Kiefer Jurij , Braig David , Winninger Oscar , Kraus Daniel , Hagelstein Salome , Eisenhardt Steffen U.
Published: June 2022

Atypical fibroxanthoma (AFX) and pleomorphic dermal sarcoma (PDS) are two distinct designations for a rare dermal sarcoma entity. These tumors arise predominantly in the sun-damaged skin of elderly patients. Although both AFX and PDS have a similar clinical presentation and nearly identical genetic features, they significantly differ in prognosis. Here we present a retrospective single-center chart review analyzing the outcomes of patients treated for dermal sarcoma. The radicality of the tumor-resection extent and soft-tissue reconstructive options were assessed. Patients between January 2010 and August 2021 were included. We recorded resection margins, tumor recurrence, overall survival, number of operations until complete tumor resection, and reconstructive procedures; any complications were recorded. Furthermore, we analyzed a subgroup of patients with satellite metastases. A total of 32 patients met the inclusion criteria (30 male, 2 female, median age of 77.5 years (interquartile range (IQR) 74–81)). Histopathology revealed AFX in 14 patients and PDS in 18 patients. Margin-free resection was achieved in 31 cases, and 27 patients were remission free over the reported period. The local recurrence rate was 5, and distant metastasis was detected in four cases. Of all the PDS cases, nine presented with satellite metastasis. No AFX had satellite metastases. Due to their rarity, managing these tumors requires an interdisciplinary setting in a specialized sarcoma center.
Ordered Mesoporous MnAlOx Oxides Dominated by Calcination Temperature for the Selective Catalytic Reduction of NOx with NH3 at Low Temperature
Authors: Hou Qixiong , Liu Yongjin , Hou Yaqin , Han Xiaojin , Huang Zhanggen
Published: June 2022

Manganese alumina composited oxides (MnAlOx) catalysts with ordered mesoporous structure prepared by evaporation-induced self-assembly (EISA) method was designed for the selective catalytic reduction (SCR) of NOx with NH3 at low temperature. The effect of calcination temperature of MnAlOx catalysts was investigated systematically, and it was correlated with SCR activity. Results showed that with an increase in calcination temperature, the SCR activity of MnAlOx catalysts increased. When the calcination temperature was raised up to 800 °C, the NOx conversion was more than 90% in the operation temperature range of 150~240 °C. Through various characterization analysis, it was found that MnAlOx-800 °C catalysts possessed enhanced redox capacities as the higher content of Mn4+/(Mn3+ + Mn4+). Moreover, the improved redox properties could contribute to a higher NOx adsorption and activation ability, which lead to higher SCR performance of MnAlOx-800 °C catalysts. In situ DRIFTs revealed that the adsorbed NO2 and bidentate nitrate are the reactive intermediate species, and NH3 species bonded to Lewis acid sites taken part in SCR progress. The SCR progress predominantly followed E–R mechanism, while L–H mechanism also takes effect to a certain degree.
Producing Natural Flavours from Isoamyl Alcohol and Fusel Oil by Using Immobilised Rhizopus oryzae Lipase
Authors: López-Fernández Josu , Benaiges Maria Dolors , Sebastian Xavier , Bueno Jose María , Valero Francisco
Published: June 2022

Enzymatic synthesis of short-chain esters (flavours) might enable their labelling as natural, increasing their value. Covalently immobilised Rhizopus oryzae lipase (EO-proROL) was used to synthesise isoamyl butyrate and acetate. In cyclohexane, the best performer reaction solvent, 1.8 times higher yield of isoamyl butyrate (ca. 100%) than isoamyl acetate (ca. 55%) was obtained. Optimum initial acid concentration (410 mM) and acid:alcohol mole ratio (0.5) were established by a central composite rotatable design to maximise isoamyl butyrate single-batch and cumulative production with reused enzyme. These conditions were used to scale up the esterification (150 mL) and to assess yield, initial esterification rate, productivity and enzyme operational stability. Commercial isoamyl alcohol and fusel oil results were found to be similar as regards yield (91% vs. 84%), initial reaction rate (5.4 µM min−1 with both substrates), operational stability (40% activity loss after five runs with both) and productivity (31.09 vs. 28.7 mM h−1). EO-proROL specificity for the structural isomers of isoamyl alcohol was also evaluated. Thus, a successful biocatalyst and product conditions ready to be used for isoamyl ester industrial production are here proposed.
IGF2: Development, Genetic and Epigenetic Abnormalities
Authors: Sélénou Céline , Brioude Frédéric , Giabicani Eloïse , Sobrier Marie-Laure , Netchine Irène
Published: June 2022

In the 30 years since the first report of parental imprinting in insulin-like growth factor 2 (Igf2) knockout mouse models, we have learnt much about the structure of this protein, its role and regulation. Indeed, many animal and human studies involving innovative techniques have shed light on the complex regulation of IGF2 expression. The physiological roles of IGF-II have also been documented, revealing pleiotropic tissue-specific and developmental-stage-dependent action. Furthermore, in recent years, animal studies have highlighted important interspecies differences in IGF-II function, gene expression and regulation. The identification of human disorders due to impaired IGF2 gene expression has also helped to elucidate the major role of IGF-II in growth and in tumor proliferation. The Silver–Russell and Beckwith–Wiedemann syndromes are the most representative imprinted disorders, as they constitute both phenotypic and molecular mirrors of IGF2-linked abnormalities. The characterization of patients with either epigenetic or genetic defects altering IGF2 expression has confirmed the central role of IGF-II in human growth regulation, particularly before birth, and its effects on broader body functions, such as metabolism or tumor susceptibility. Given the long-term health impact of these rare disorders, it is important to understand the consequences of IGF2 defects in these patients.
Lethal and Non-Lethal Functions of Caspases in the DNA Damage Response
Authors: Lopez Karla E. , Bouchier-Hayes Lisa
Published: June 2022

Members of the caspase family are well known for their roles in the initiation and execution of cell death. Due to their function in the removal of damaged cells that could otherwise become malignant, caspases are important players in the DNA damage response (DDR), a network of pathways that prevent genomic instability. However, emerging evidence of caspases positively or negatively impacting the accumulation of DNA damage in the absence of cell death demonstrates that caspases play a role in the DDR that is independent of their role in apoptosis. This review highlights the apoptotic and non-apoptotic roles of caspases in the DDR and how they can impact genomic stability and cancer treatment.
Synthetic Thymidine Analog Labeling without Misconceptions
Authors: Ivanova Anna , Gruzova Olesya , Ermolaeva Elizaveta , Astakhova Olga , Itaman Sheed , Enikolopov Grigori , Lazutkin Alexander
Published: June 2022

Tagging proliferating cells with thymidine analogs is an indispensable research tool; however, the issue of the potential in vivo cytotoxicity of these compounds remains unresolved. Here, we address these concerns by examining the effects of BrdU and EdU on adult hippocampal neurogenesis and EdU on the perinatal somatic development of mice. We show that, in a wide range of doses, EdU and BrdU label similar numbers of cells in the dentate gyrus shortly after administration. Furthermore, whereas the administration of EdU does not affect the division and survival of neural progenitor within 48 h after injection, it does affect cell survival, as evaluated 6 weeks later. We also show that a single injection of various doses of EdU on the first postnatal day does not lead to noticeable changes in a panel of morphometric criteria within the first week; however, higher doses of EdU adversely affect the subsequent somatic maturation and brain growth of the mouse pups. Our results indicate the potential caveats in labeling the replicating DNA using thymidine analogs and suggest guidelines for applying this approach.
The Influence of PARP, ATR, CHK1 Inhibitors on Premature Mitotic Entry and Genomic Instability in High-Grade Serous BRCAMUT and BRCAWT Ovarian Cancer Cells
Authors: Gralewska Patrycja , Gajek Arkadiusz , Rybaczek Dorota , Marczak Agnieszka , Rogalska Aneta
Published: June 2022

Olaparib is a poly (ADP-ribose) polymerase inhibitor (PARPi) that inhibits PARP1/2, leading to replication-induced DNA damage that requires homologous recombination repair. Olaparib is often insufficient to treat BRCA-mutated (BRCAMUT) and BRCA wild-type (BRCAWT) high-grade serous ovarian carcinomas (HGSOCs). We examined the short-term (up to 48 h) efficacy of PARPi treatment on a DNA damage response pathway mediated by ATR and CHK1 kinases in BRCAMUT (PEO-1) and BRCAWT (SKOV-3 and OV-90) cells. The combination of ATRi/CHK1i with PARPi was not more cytotoxic than ATR and CHK1 monotherapy. The combination of olaparib with inhibitors of the ATR/CHK1 pathway generated chromosomal abnormalities, independent on BRCAMUT status of cells and formed of micronuclei (MN). However, the beneficial effect of the PARPi:ATRi combination on MN was seen only in the PEO1 BRCAMUT line. Monotherapy with ATR/CHK1 inhibitors reduced BrdU incorporation due to a slower rate of DNA synthesis, which resulted from elevated levels of replication stress, while simultaneous blockade of PARP and ATR caused beneficial effects only in OV-90 cells. Inhibition of ATR/CHK1 increased the formation of double-strand breaks as measured by increased γH2AX expression at collapsed replication forks, resulting in increased levels of apoptosis. Our findings indicate that ATR and CHK1 inhibitors provoke premature mitotic entry, leading to genomic instability and ultimately cell death.
Systemic Ablation of Camkk2 Impairs Metastatic Colonization and Improves Insulin Sensitivity in TRAMP Mice: Evidence for Cancer Cell-Extrinsic CAMKK2 Functions in Prostate Cancer
Authors: Pulliam Thomas L. , Awad Dominik , Han Jenny J. , Murray Mollianne M. , Ackroyd Jeffrey J. , Goli Pavithr , Oakhill Jonathan S. , Scott John W. , Ittmann Michael M. , Frigo Daniel E.
Published: June 2022

Despite early studies linking calcium-calmodulin protein kinase kinase 2 (CAMKK2) to prostate cancer cell migration and invasion, the role of CAMKK2 in metastasis in vivo remains unclear. Moreover, while CAMKK2 is known to regulate systemic metabolism, whether CAMKK2’s effects on whole-body metabolism would impact prostate cancer progression and/or related comorbidities is not known. Here, we demonstrate that germline ablation of Camkk2 slows, but does not stop, primary prostate tumorigenesis in the TRansgenic Adenocarcinoma Mouse Prostate (TRAMP) genetic mouse model. Consistent with prior epidemiological reports supporting a link between obesity and prostate cancer aggressiveness, TRAMP mice fed a high-fat diet exhibited a pronounced increase in the colonization of lung metastases. We demonstrated that this effect on the metastatic spread was dependent on CAMKK2. Notably, diet-induced lung metastases exhibited a highly aggressive neuroendocrine phenotype. Concurrently, Camkk2 deletion improved insulin sensitivity in the same mice. Histological analyses revealed that cancer cells were smaller in the TRAMP;Camkk2−/− mice compared to TRAMP;Camkk2+/+ controls. Given the differences in circulating insulin levels, a known regulator of cell growth, we hypothesized that systemic CAMKK2 could promote prostate cancer cell growth and disease progression in part through cancer cell-extrinsic mechanisms. Accordingly, host deletion of Camkk2 impaired the growth of syngeneic murine prostate tumors in vivo, confirming nonautonomous roles for CAMKK2 in prostate cancer. Cancer cell size and mTOR signaling was diminished in tumors propagated in Camkk2-null mice. Together, these data indicate that, in addition to cancer cell-intrinsic roles, CAMKK2 mediates prostate cancer progression via tumor-extrinsic mechanisms. Further, we propose that CAMKK2 inhibition may also help combat common metabolic comorbidities in men with advanced prostate cancer.
Characterization of Severity in Zellweger Spectrum Disorder by Clinical Findings: A Scoping Review, Meta-Analysis and Medical Chart Review
Authors: Bose Mousumi , Yergeau Christine , D’Souza Yasmin , Cuthbertson David D. , Lopez Melisa J. , Smolen Alyssa K. , Braverman Nancy E.
Published: June 2022

Zellweger spectrum disorder (ZSD) is a rare, debilitating genetic disorder of peroxisome biogenesis that affects multiple organ systems and presents with broad clinical heterogeneity. Although severe, intermediate, and mild forms of ZSD have been described, these designations are often arbitrary, presenting difficulty in understanding individual prognosis and treatment effectiveness. The purpose of this study is to conduct a scoping review and meta-analysis of existing literature and a medical chart review to determine if characterization of clinical findings can predict severity in ZSD. Our PubMed search for articles describing severity, clinical findings, and survival in ZSD resulted in 107 studies (representing 307 patients) that were included in the review and meta-analysis. We also collected and analyzed these same parameters from medical records of 136 ZSD individuals from our natural history study. Common clinical findings that were significantly different across severity categories included seizures, hypotonia, reduced mobility, feeding difficulties, renal cysts, adrenal insufficiency, hearing and vision loss, and a shortened lifespan. Our primary data analysis also revealed significant differences across severity categories in failure to thrive, gastroesophageal reflux, bone fractures, global developmental delay, verbal communication difficulties, and cardiac abnormalities. Univariable multinomial logistic modeling analysis of clinical findings and very long chain fatty acid (VLCFA) hexacosanoic acid (C26:0) levels showed that the number of clinical findings present among seizures, abnormal EEG, renal cysts, and cardiac abnormalities, as well as plasma C26:0 fatty acid levels could differentiate severity categories. We report the largest characterization of clinical findings in relation to overall disease severity in ZSD. This information will be useful in determining appropriate outcomes for specific subjects in clinical trials for ZSD.